Toxins

20 pages, 595 KiB

Open AccessEditor’s ChoiceArticle

Suppressing Cyanobacteria with Hydrogen Peroxide Is More Effective at High Light Intensities

by Tim Piel, Giovanni Sandrini, Emily White, Tianshuo Xu, J. Merijn Schuurmans, Jef Huisman and Petra M. Visser

Toxins 2020, 12(1), 18; https://doi.org/10.3390/toxins12010018 - 31 Dec 2019

Cited by 45 | Viewed by 6738

Abstract

Hydrogen peroxide (H₂O₂) can be used as an emergency method to selectively suppress cyanobacterial blooms in lakes and drinking water reservoirs. However, it is largely unknown how environmental parameters alter the effectiveness of H₂O₂ treatments. In [...] Read more.

Hydrogen peroxide (H₂O₂) can be used as an emergency method to selectively suppress cyanobacterial blooms in lakes and drinking water reservoirs. However, it is largely unknown how environmental parameters alter the effectiveness of H₂O₂ treatments. In this study, the toxic cyanobacterial strain Microcystis aeruginosa PCC 7806 was treated with a range of H₂O₂ concentrations (0 to 10 mg/L), while being exposed to different light intensities and light colors. H₂O₂ treatments caused a stronger decline of the photosynthetic yield in high light than in low light or in the dark, and also a stronger decline in orange than in blue light. Our results are consistent with the hypothesis that H₂O₂ causes major damage at photosystem II (PSII) and interferes with PSII repair, which makes cells more sensitive to photoinhibition. Furthermore, H₂O₂ treatments caused a decrease in cell size and an increase in extracellular microcystin concentrations, indicative of leakage from disrupted cells. Our findings imply that even low H₂O₂ concentrations of 1–2 mg/L can be highly effective, if cyanobacteria are exposed to high light intensities. We therefore recommend performing lake treatments during sunny days, when a low H₂O₂ dosage is sufficient to suppress cyanobacteria, and may help to minimize impacts on non-target organisms. Full article

(This article belongs to the Special Issue Selected Papers from the 11th International Conference on Toxic Cyanobacteria)

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23 pages, 4732 KiB

Open AccessEditor’s ChoiceReview

Two-Dimensional Layered Nanomaterial-Based Electrochemical Biosensors for Detecting Microbial Toxins

by Zhuheng Li, Xiaotong Li, Minghong Jian, Girma Selale Geleta and Zhenxin Wang

Toxins 2020, 12(1), 20; https://doi.org/10.3390/toxins12010020 - 31 Dec 2019

Cited by 36 | Viewed by 6165

Abstract

Toxin detection is an important issue in numerous fields, such as agriculture/food safety, environmental monitoring, and homeland security. During the past two decades, nanotechnology has been extensively used to develop various biosensors for achieving fast, sensitive, selective and on-site analysis of toxins. In [...] Read more.

Toxin detection is an important issue in numerous fields, such as agriculture/food safety, environmental monitoring, and homeland security. During the past two decades, nanotechnology has been extensively used to develop various biosensors for achieving fast, sensitive, selective and on-site analysis of toxins. In particular, the two dimensional layered (2D) nanomaterials (such as graphene and transition metal dichalcogenides (TMDs)) and their nanocomposites have been employed as label and/or biosensing transducers to construct electrochemical biosensors for cost-effective detection of toxins with high sensitivity and specificity. This is because the 2D nanomaterials have good electrical conductivity and a large surface area with plenty of active groups for conjugating 2D nanomaterials with the antibodies and/or aptamers of the targeted toxins. Herein, we summarize recent developments in the application of 2D nanomaterial-based electrochemical biosensors for detecting toxins with a particular focus on microbial toxins including bacterial toxins, fungal toxins and algal toxins. The integration of 2D nanomaterials with some existing antibody/aptamer technologies into electrochemical biosensors has led to an unprecedented impact on improving the assaying performance of microbial toxins, and has shown great promise in public health and environmental protection. Full article

(This article belongs to the Special Issue Improved Analytical Technologies for the Detection of Natural Toxins and Their Metabolites in Food)

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16 pages, 1177 KiB

Open AccessEditor’s ChoiceArticle

Potential Application of Lactic Acid Bacteria to Reduce Aflatoxin B₁ and Fumonisin B₁ Occurrence on Corn Kernels and Corn Ears

by Tiago de Melo Nazareth, Carlos Luz, Raquel Torrijos, Juan Manuel Quiles, Fernando Bittencourt Luciano, Jordi Mañes and Giuseppe Meca

Toxins 2020, 12(1), 21; https://doi.org/10.3390/toxins12010021 - 31 Dec 2019

Cited by 62 | Viewed by 5378

Abstract

Fungal spoilage is an important issue for the food industry, leading to food sensory defects, food waste, economic losses and public health concern through the production of mycotoxins. Concomitantly, the search for safer natural products has gained importance since consumers began to look [...] Read more.

Fungal spoilage is an important issue for the food industry, leading to food sensory defects, food waste, economic losses and public health concern through the production of mycotoxins. Concomitantly, the search for safer natural products has gained importance since consumers began to look for less processed and chemically treated foods. In this context, the aim of this study was to evaluate the antifungal and antimycotoxigenic effect of seven strains of Lactobacillus plantarum. Lactic acid bacteria (LAB) were grown on Man Rogosa Sharpe (MRS) broth at 37 °C in anaerobic conditions. After that, the cell-free supernatant (CFS) were recovered to determine its antifungal activity by halo diffusion agar test. In addition, minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) was determined for each L. plantarum CFS by 96-well microplates method. Additionally, CFS was used as a natural biocontrol agent on corn kernels and corn ears contaminated with Aspergillus flavus and Fusarium verticillioides, respectively. The L. plantarum CECT 749 CFS showed the highest antifungal effect against all essayed strains. Moreover, the employment of this CFS in food reduced the mycotoxin production at a percentage ranging from 73.7 to 99.7%. These results suggest that the L. plantarum CECT 749 CFS could be promising for the biocontrol of corn. Full article

(This article belongs to the Special Issue Aflatoxins: Food Sources, Occurrence and Toxicological Effects)

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15 pages, 3082 KiB

Open AccessEditor’s ChoiceArticle

Inflammasome Activation Induced by a Snake Venom Lys49-Phospholipase A₂ Homologue

by Charles Nunes Boeno, Mauro Valentino Paloschi, Jéssica Amaral Lopes, Weverson Luciano Pires, Sulamita da Silva Setúbal, Jaína Rodrigues Evangelista, Andreimar Martins Soares and Juliana Pavan Zuliani

Toxins 2020, 12(1), 22; https://doi.org/10.3390/toxins12010022 - 31 Dec 2019

Cited by 28 | Viewed by 4689

Abstract

Background: Snake venom phospholipases A₂ (PLA₂s) have hemolytic, anticoagulant, myotoxic, oedematogenic, bactericidal, and inflammatory actions. BthTX-I, a Lys49-PLA₂ isolated from Bothrops jararacussu venom, is an example of Lys49-PLA₂ that presents such actions. NLRP3 is a cytosolic receptor from [...] Read more.

Background: Snake venom phospholipases A₂ (PLA₂s) have hemolytic, anticoagulant, myotoxic, oedematogenic, bactericidal, and inflammatory actions. BthTX-I, a Lys49-PLA₂ isolated from Bothrops jararacussu venom, is an example of Lys49-PLA₂ that presents such actions. NLRP3 is a cytosolic receptor from the NLR family responsible for inflammasome activation via caspase-1 activation and IL-1β liberation. The study of NLRs that recognize tissue damage and activate the inflammasome is relevant in envenomation. Methods: Male mice (18–20 g) received an intramuscular injection of BthTX-I or sterile saline. The serum was collected for creatine-kinase (CK), lactate dehydrogenase (LDH), and interleukin-1β (IL-1β) assays, and muscle was removed for inflammasome activation immunoblotting and qRT-PCR expression for nucleotide and oligomerization domain, leucine-rich repeat-containing protein family, pyrin-containing domain 3 receptor (NLRP3) inflammasome components. Results: BthTX-I-induced inflammation and myonecrosis, shown by intravital microscope, and LDH and CK release, respectively. Mouse treatment with A438079, a P2X7 receptor antagonist, did not modify these effects. BthTX-I induced inflammasome activation in muscle, but P2X7R participation in this effect was not observed. Conclusion: Together, the results showed for the first time that BthTX-I in gastrocnemius muscle induces inflammation and consequently, inflammasome activation via NLRP3 with caspase-1 activation and IL-1β liberation. Full article

(This article belongs to the Section Animal Venoms)

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24 pages, 846 KiB

Open AccessEditor’s ChoiceReview

Public Health Risk Associated with Botulism as Foodborne Zoonoses

by Christine Rasetti-Escargueil, Emmanuel Lemichez and Michel R. Popoff

Toxins 2020, 12(1), 17; https://doi.org/10.3390/toxins12010017 - 30 Dec 2019

Cited by 63 | Viewed by 14451

Abstract

Botulism is a rare but severe neurological disease in man and animals that is caused by botulinum neurotoxins (BoNTs) produced by Clostridium botulinum and atypical strains from other Clostridium and non-Clostridium species. BoNTs are divided into more than seven toxinotypes based on [...] Read more.

Botulism is a rare but severe neurological disease in man and animals that is caused by botulinum neurotoxins (BoNTs) produced by Clostridium botulinum and atypical strains from other Clostridium and non-Clostridium species. BoNTs are divided into more than seven toxinotypes based on neutralization with specific corresponding antisera, and each toxinotype is subdivided into subtypes according to amino acid sequence variations. Animal species show variable sensitivity to the different BoNT toxinotypes. Thereby, naturally acquired animal botulism is mainly due to BoNT/C, D and the mosaic variants CD and DC, BoNT/CD being more prevalent in birds and BoNT/DC in cattle, whereas human botulism is more frequently in the types A, B and E, and to a lower extent, F. Botulism is not a contagious disease, since there is no direct transmission from diseased animals or man to a healthy subject. Botulism occurs via the environment, notably from food contaminated with C. botulinum spores and preserved in conditions favorable for C. botulinum growth and toxin production. The high prevalence of botulism types C, D and variants DC and CD in farmed and wild birds, and to a lower extent in cattle, raises the risk of transmission to human beings. However, human botulism is much rarer than animal botulism, and botulism types C and D are exceptional in humans. Only 15 cases or suspected cases of botulism type C and one outbreak of botulism type D have been reported in humans to date. In contrast, animal healthy carriers of C. botulinum group II, such as C. botulinum type E in fish of the northern hemisphere, and C. botulinum B4 in pigs, represent a more prevalent risk of botulism transmission to human subjects. Less common botulism types in animals but at risk of transmission to humans, can sporadically be observed, such as botulism type E in farmed chickens in France (1998–2002), botulism type B in cattle in The Netherlands (1977–1979), botulism types A and B in horses, or botulism type A in dairy cows (Egypt, 1976). In most cases, human and animal botulisms have distinct origins, and cross transmissions between animals and human beings are rather rare, accidental events. But, due to the severity of this disease, human and animal botulism requires a careful surveillance. Full article

(This article belongs to the Special Issue New Challenges in Foodborne Botulism Outbreaks)

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17 pages, 5501 KiB

Open AccessEditor’s ChoiceArticle

Dereplication of Natural Products with Antimicrobial and Anticancer Activity from Brazilian Cyanobacteria

by Tania Keiko Shishido, Rafael Vicentini Popin, Jouni Jokela, Matti Wahlsten, Marli Fatima Fiore, David P. Fewer, Lars Herfindal and Kaarina Sivonen

Toxins 2020, 12(1), 12; https://doi.org/10.3390/toxins12010012 - 24 Dec 2019

Cited by 34 | Viewed by 7396

Abstract

Cyanobacteria are photosynthetic organisms that produce a large diversity of natural products with interesting bioactivities for biotechnological and pharmaceutical applications. Cyanobacterial extracts exhibit toxicity towards other microorganisms and cancer cells and, therefore, represent a source of potentially novel natural products for drug discovery. [...] Read more.

Cyanobacteria are photosynthetic organisms that produce a large diversity of natural products with interesting bioactivities for biotechnological and pharmaceutical applications. Cyanobacterial extracts exhibit toxicity towards other microorganisms and cancer cells and, therefore, represent a source of potentially novel natural products for drug discovery. We tested 62 cyanobacterial strains isolated from various Brazilian biomes for antileukemic and antimicrobial activities. Extracts from 39 strains induced selective apoptosis in acute myeloid leukemia (AML) cancer cell lines. Five of these extracts also exhibited antifungal and antibacterial activities. Chemical and dereplication analyses revealed the production of nine known natural products. Natural products possibly responsible for the observed bioactivities and five unknown, chemically related chlorinated compounds present only in Brazilian cyanobacteria were illustrated in a molecular network. Our results provide new information on the vast biosynthetic potential of cyanobacteria isolated from Brazilian environments. Full article

(This article belongs to the Special Issue Biosynthesis, Accumulation, and Bioactivity of Secondary Metabolites in Cyanobacteria)

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9 pages, 408 KiB

Open AccessEditor’s ChoiceArticle

Serum P-Cresyl Sulfate Is a Predictor of Central Arterial Stiffness in Patients on Maintenance Hemodialysis

by Yu-Hsien Lai, Chih-Hsien Wang, Chiu-Huang Kuo, Yu-Li Lin, Jen-Pi Tsai and Bang-Gee Hsu

Toxins 2020, 12(1), 10; https://doi.org/10.3390/toxins12010010 - 21 Dec 2019

Cited by 20 | Viewed by 2979

Abstract

Arterial stiffness (AS) has an important impact on the outcomes of patients on hemodialysis (HD), and p-cresyl sulfate (PC) can mediate the process of vascular damage. We aimed to investigate the relationship between carotid–femoral pulse wave velocity (cfPWV) and the level of [...] Read more.

Arterial stiffness (AS) has an important impact on the outcomes of patients on hemodialysis (HD), and p-cresyl sulfate (PC) can mediate the process of vascular damage. We aimed to investigate the relationship between carotid–femoral pulse wave velocity (cfPWV) and the level of PCs in HD patients. Serum PCs were quantified using liquid chromatography mass spectrometry. Patients who were on standard HD for more than 3 months were enrolled and categorized according to the cfPWV into the high AS (>10 m/s) and control (≤10 m/s) groups. Forty-nine (41.5%) patients belonged to the high AS group and had a higher incidence of diabetes mellitus (DM) and increased systolic blood pressure, serum C-reactive protein, and PC levels but had lower creatinine, compared with those in the control group. In HD patients, the risk for developing high AS increased in the presence of DM (OR 4.147, 95% confidence interval (CI) 1.497–11.491) and high PCs (OR 1.067, 95% CI 1.002–1.136). Having DM (r = 0.446) and high PC level (r = 0.174) were positively associated with cfPWV. The most optimal cutoff value of PC for predicting AS was 18.99 mg/L (area under the curve 0.661, 95% CI 0.568–0.746). We concluded that DM and PCs were promising predictors of high AS in patients on maintenance HD. Full article

(This article belongs to the Special Issue Comorbidities in Chronic Kidney Disease (CKD))

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15 pages, 662 KiB

Open AccessEditor’s ChoiceReview

A Review on the Study of Cyanotoxins in Paleolimnological Research: Current Knowledge and Future Needs

by Eliana Henao, Piotr Rzymski and Matthew N. Waters

Toxins 2020, 12(1), 6; https://doi.org/10.3390/toxins12010006 - 20 Dec 2019

Cited by 24 | Viewed by 5186

Abstract

Cyanobacterial metabolites are increasingly studied, in regards to their biosynthesis, ecological role, toxicity, and potential biomedical applications. However, the history of cyanotoxins prior to the last few decades is virtually unknown. Only a few paleolimnological studies have been undertaken to date, and these [...] Read more.

Cyanobacterial metabolites are increasingly studied, in regards to their biosynthesis, ecological role, toxicity, and potential biomedical applications. However, the history of cyanotoxins prior to the last few decades is virtually unknown. Only a few paleolimnological studies have been undertaken to date, and these have focused exclusively on microcystins and cylindrospermopsins, both successfully identified in lake sediments up to 200 and 4700 years old, respectively. In this paper, we review direct extraction, quantification, and application of cyanotoxins in sediment cores, and put forward future research prospects in this field. Cyanobacterial toxin research is also compared to other paleo-cyanobacteria tools, such as sedimentary pigments, akinetes, and ancient DNA isolation, to identify the role of each tool in reproducing the history of cyanobacteria. Such investigations may also be beneficial for further elucidation of the biological role of cyanotoxins, particularly if coupled with analyses of other abiotic and biotic sedimentary features. In addition, we identify current limitations as well as future directions for applications in the field of paleolimnological studies on cyanotoxins. Full article

(This article belongs to the Special Issue Biological Role of Cyanotoxins: Experimental and In-Field Evidence)

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26 pages, 3207 KiB

Open AccessEditor’s ChoiceReview

Fumagillin, a Mycotoxin of Aspergillus fumigatus: Biosynthesis, Biological Activities, Detection, and Applications

by Xabier Guruceaga, Uxue Perez-Cuesta, Ana Abad-Diaz de Cerio, Oskar Gonzalez, Rosa M. Alonso, Fernando Luis Hernando, Andoni Ramirez-Garcia and Aitor Rementeria

Toxins 2020, 12(1), 7; https://doi.org/10.3390/toxins12010007 - 20 Dec 2019

Cited by 61 | Viewed by 11809

Abstract

Fumagillin is a mycotoxin produced, above all, by the saprophytic filamentous fungus Aspergillus fumigatus. This mold is an opportunistic pathogen that can cause invasive aspergillosis, a disease that has high mortality rates linked to it. Its ability to adapt to environmental stresses [...] Read more.

Fumagillin is a mycotoxin produced, above all, by the saprophytic filamentous fungus Aspergillus fumigatus. This mold is an opportunistic pathogen that can cause invasive aspergillosis, a disease that has high mortality rates linked to it. Its ability to adapt to environmental stresses through the production of secondary metabolites, including several mycotoxins (gliotoxin, fumagillin, pseurotin A, etc.) also seem to play an important role in causing these infections. Since the discovery of the A. fumigatus fumagillin in 1949, many studies have focused on this toxin and in this review we gather all the information currently available. First of all, the structural characteristics of this mycotoxin and the different methods developed for its determination are given in detail. Then, the biosynthetic gene cluster and the metabolic pathway involved in its production and regulation are explained. The activity of fumagillin on its target, the methionine aminopeptidase type 2 (MetAP2) enzyme, and the effects of blocking this enzyme in the host are also described. Finally, the applications that this toxin and its derivatives have in different fields, such as the treatment of cancer and its microsporicidal activity in the treatment of honeybee hive infections with Nosema spp., are reviewed. Therefore, this work offers a complete review of all the information currently related to the fumagillin mycotoxin secreted by A. fumigatus, important because of its role in the fungal infection process but also because it has many other applications, notably in beekeeping, the treatment of infectious diseases, and in oncology. Full article

(This article belongs to the Special Issue Mycotoxin Biosynthesis and Genetic Transformation Systems in Fungi)

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14 pages, 6161 KiB

Open AccessEditor’s ChoiceArticle

The Novel Clostridial Neurotoxin Produced by Strain IBCA10-7060 Is Immunologically Equivalent to BoNT/HA

by Yongfeng Fan, Jason R. Barash, Fraser Conrad, Jianlong Lou, Christina Tam, Luisa W. Cheng, Stephen S. Arnon and James D. Marks

Toxins 2020, 12(1), 9; https://doi.org/10.3390/toxins12010009 - 20 Dec 2019

Cited by 19 | Viewed by 3820

Abstract

Background: Botulinum neurotoxins (BoNTs) comprise seven agreed-on serotypes, A through G. In 2014, a novel chimeric neurotoxin produced by clostridial strain IBCA10-7060 was reported as BoNT/H, with subsequent names of BoNT/FA or BoNT/HA based on sequence homology of the N-terminus to BoNT/F, the [...] Read more.

Background: Botulinum neurotoxins (BoNTs) comprise seven agreed-on serotypes, A through G. In 2014, a novel chimeric neurotoxin produced by clostridial strain IBCA10-7060 was reported as BoNT/H, with subsequent names of BoNT/FA or BoNT/HA based on sequence homology of the N-terminus to BoNT/F, the C-terminus to BoNT/A and neutralization studies. The purpose of this study was to define the immunologic identity of the novel BoNT. Methods: monoclonal antibodies (mAbs) to the novel BoNT/H N-terminus were generated by antibody repertoire cloning and yeast display after immunization with BoNT/H LC-H_N or BoNT/F LC-H_N. Results: 21 unique BoNT/H LC-H_N mAbs were obtained; 15 from the BoNT/H LC-H_N immunized library (K_D 0.78 nM to 182 nM) and six from the BoNT/F-immunized libraries (K_D 20.5 nM to 1490 nM). A total of 15 of 21 mAbs also bound catalytically inactive BoNT/H holotoxin. The mAbs bound nine non-overlapping epitopes on the BoNT/H LC-H_N. None of the mAbs showed binding to BoNT serotypes A-G, nor any of the seven subtypes of BoNT/F, except for one mAb that weakly bound BoNT/F5. Conclusions: The results, combined with the chimeric structure and neutralization by anti-A, but not anti-F antitoxin indicate that immunologically the novel BoNT is BoNT/HA. This determination has significant implications for existing countermeasures and potential vulnerabilities. Full article

(This article belongs to the Section Bacterial Toxins)

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23 pages, 1793 KiB

Open AccessEditor’s ChoiceArticle

Intraspecific Variability in the Toxin Production and Toxin Profiles of In Vitro Cultures of Gambierdiscus polynesiensis (Dinophyceae) from French Polynesia

by Sébastien Longo, Manoella Sibat, Jérôme Viallon, Hélène Taiana Darius, Philipp Hess and Mireille Chinain

Toxins 2019, 11(12), 735; https://doi.org/10.3390/toxins11120735 - 17 Dec 2019

Cited by 43 | Viewed by 5275

Abstract

Ciguatera poisoning (CP) is a foodborne disease caused by the consumption of seafood contaminated with ciguatoxins (CTXs) produced by dinoflagellates in the genera Gambierdiscus and Fukuyoa. The toxin production and toxin profiles were explored in four clones of G. polynesiensis originating from [...] Read more.

Ciguatera poisoning (CP) is a foodborne disease caused by the consumption of seafood contaminated with ciguatoxins (CTXs) produced by dinoflagellates in the genera Gambierdiscus and Fukuyoa. The toxin production and toxin profiles were explored in four clones of G. polynesiensis originating from different islands in French Polynesia with contrasted CP risk: RIK7 (Mangareva, Gambier), NHA4 (Nuku Hiva, Marquesas), RAI-1 (Raivavae, Australes), and RG92 (Rangiroa, Tuamotu). Productions of CTXs, maitotoxins (MTXs), and gambierone group analogs were examined at exponential and stationary growth phases using the neuroblastoma cell-based assay and liquid chromatography–tandem mass spectrometry. While none of the strains was found to produce known MTX compounds, all strains showed high overall P-CTX production ranging from 1.1 ± 0.1 to 4.6 ± 0.7 pg cell⁻¹. In total, nine P-CTX analogs were detected, depending on strain and growth phase. The production of gambierone, as well as 44-methylgamberione, was also confirmed in G. polynesiensis. This study highlighted: (i) intraspecific variations in toxin production and profiles between clones from distinct geographic origins and (ii) the noticeable increase in toxin production of both CTXs, in particular CTX4A/B, and gambierone group analogs from the exponential to the stationary phase. Full article

(This article belongs to the Special Issue Potentially Toxic Benthic Microorganisms in Freshwater and Marine Ecosystems)

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13 pages, 8640 KiB

Open AccessEditor’s ChoiceArticle

Deoxynivalenol Induces Inflammatory Injury in IPEC-J2 Cells via NF-κB Signaling Pathway

by Xichun Wang, Yafei Zhang, Jie Zhao, Li Cao, Lei Zhu, Yingying Huang, Xiaofang Chen, Sajid Ur Rahman, Shibin Feng, Yu Li and Jinjie Wu

Toxins 2019, 11(12), 733; https://doi.org/10.3390/toxins11120733 - 16 Dec 2019

Cited by 33 | Viewed by 4529

Abstract

The aim of this study was to investigate the effects of deoxynivalenol (DON) exposure on the inflammatory injury nuclear factor kappa-B (NF-κB) pathway in intestinal epithelial cells (IPEC-J2 cells) of pig. The different concentrations of DON (0, 125, 250, 500, 1000, 2000 ng/mL) [...] Read more.

The aim of this study was to investigate the effects of deoxynivalenol (DON) exposure on the inflammatory injury nuclear factor kappa-B (NF-κB) pathway in intestinal epithelial cells (IPEC-J2 cells) of pig. The different concentrations of DON (0, 125, 250, 500, 1000, 2000 ng/mL) were added to the culture solution for treatment. The NF-κB pathway inhibitor pyrrolidine dithiocarbamate (PDTC) was used as a reference. The results showed that when the DON concentration increased, the cell density decreased and seemed damaged. With the increase of DON concentration in the culture medium, the action of diamine oxidase (DAO) in the culture supernatant also increased. The activities of IL-6, TNF-α, and NO in the cells were increased with the increasing DON concentration. The relative mRNA expression of IL-1β and IL-6 were increased in the cells. The mRNA relative expression of NF-κB p65, IKKα, and IKKβ were upregulated with the increasing of DON concentration, while the relative expression of IκB-α mRNA was downregulated. At the same time, the expression of NF-κB p65 protein increased gradually in the cytoplasm and nucleus with a higher concentration of DON. These results showed that DON could change the morphology of IPEC-J2 cells, destroy its submicroscopic structure, and enhance the permeability of cell membrane, as well as upregulate the transcription of some inflammatory factors and change the expression of NF-κB-related gene or protein in cells. Full article

(This article belongs to the Special Issue Mycotoxins Occurence in Feed and Their Influence on Animal Health)

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17 pages, 341 KiB

Open AccessEditor’s ChoiceReview

The Therapeutic Effects and Pathophysiology of Botulinum Toxin A on Voiding Dysfunction Due to Urethral Sphincter Dysfunction

by Yao-Lin Kao, Kuan-Hsun Huang, Hann-Chorng Kuo and Yin-Chien Ou

Toxins 2019, 11(12), 728; https://doi.org/10.3390/toxins11120728 - 13 Dec 2019

Cited by 23 | Viewed by 4215

Abstract

Neurogenic and non-neurogenic urethral sphincter dysfunction are common causes of voiding dysfunction. Injections of botulinum toxin A (BoNT-A) into the urethral sphincter have been used to treat urethral sphincter dysfunction (USD) refractory to conventional treatment. Since its first use for patients with detrusor [...] Read more.

Neurogenic and non-neurogenic urethral sphincter dysfunction are common causes of voiding dysfunction. Injections of botulinum toxin A (BoNT-A) into the urethral sphincter have been used to treat urethral sphincter dysfunction (USD) refractory to conventional treatment. Since its first use for patients with detrusor sphincter dyssynergia in 1988, BoNT-A has been applied to various causes of USD, including dysfunctional voiding, Fowler’s syndrome, and poor relaxation of the external urethral sphincter. BoNT-A is believed to decrease urethral resistance via paralysis of the striated sphincter muscle through inhibition of acetylcholine release in the neuromuscular junction. Recovery of detrusor function in patients with detrusor underactivity combined with a hyperactive sphincter also suggested the potential neuromodulation effect of sphincteric BoNT-A injection. A large proportion of patients with different causes of USD report significant improvement in voiding after sphincteric BoNT-A injections. However, patient satisfaction might not increase with an improvement in the symptoms because of concomitant side effects including exacerbated incontinence, urinary urgency, and over-expectation. Nonetheless, in terms of efficacy and safety, BoNT-A is still a reasonable option for refractory voiding function. To date, studies focusing on urethral sphincter BoNT-A injections have been limited to the heterogeneous etiologies of USD. Further well-designed studies are thus needed. Full article

(This article belongs to the Special Issue Botulinum Toxin Treatment for Pain and Inflammation in Functional Urological Disorders)

12 pages, 1376 KiB

Open AccessEditor’s ChoiceArticle

Measurement of Microcystin and Nodularin Activity in Human Urine by Immunocapture-Protein Phosphatase 2A Assay

by Rebekah E. Wharton, Brady R. Cunningham, Adam M. Schaefer, Sophia M. Guldberg, Elizabeth I. Hamelin and Rudolph C. Johnson

Toxins 2019, 11(12), 729; https://doi.org/10.3390/toxins11120729 - 13 Dec 2019

Cited by 18 | Viewed by 8993

Abstract

Microcystins (MC) and nodularin (NOD) are toxins released by cyanobacteria during harmful algal blooms. They are potent inhibitors of protein phosphatases 1 and 2A (PP1 and PP2A) and cause a variety of adverse symptoms in humans and animals if ingested. More than 250 [...] Read more.

Microcystins (MC) and nodularin (NOD) are toxins released by cyanobacteria during harmful algal blooms. They are potent inhibitors of protein phosphatases 1 and 2A (PP1 and PP2A) and cause a variety of adverse symptoms in humans and animals if ingested. More than 250 chemically diverse congeners of MCs have been identified, but certified reference materials are only available for a few. A diagnostic test that does not require each reference material for detection is necessary to identify human exposures. To address this need, our lab has developed a method that uses an antibody to specifically isolate MCs and NOD from urine prior to detection via a commercially available PP2A kit. This assay quantitates the summed inhibitory activity of nearly all MCs and NOD on PP2A relative to a common MC congener, microcystin-LR (MC-LR). The quantitation range for MC-LR using this method is from 0.050–0.500 ng/mL. No background responses were detected in a convenience set of 50 individual urines. Interday and intraday % accuracies ranged from 94%–118% and relative standard deviations were 15% or less, meeting FDA guidelines for receptor binding assays. The assay detected low levels of MCs in urines from three individuals living in close proximity to harmful algal blooms (HABs) in Florida. Full article

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20 pages, 7541 KiB

Open AccessEditor’s ChoiceArticle

The Cytotoxicity Effect of Resveratrol: Cell Cycle Arrest and Induced Apoptosis of Breast Cancer 4T1 Cells

by Hong Wu, Liang Chen, Feifei Zhu, Xu Han, Lindan Sun and Keping Chen

Toxins 2019, 11(12), 731; https://doi.org/10.3390/toxins11120731 - 13 Dec 2019

Cited by 138 | Viewed by 13614

Abstract

Resveratrol, a natural polyterpenoid, can scavenge reactive oxygen species in vivo to carry out the functions of antioxidation and antiaging. Resveratrol’s anti-cancer capability has attracted widespread attention, but its molecular mechanism has not been systematically explained. In this study, by comparing the activity [...] Read more.

Resveratrol, a natural polyterpenoid, can scavenge reactive oxygen species in vivo to carry out the functions of antioxidation and antiaging. Resveratrol’s anti-cancer capability has attracted widespread attention, but its molecular mechanism has not been systematically explained. In this study, by comparing the activity of normal cell lines and cancer cell lines after treating with resveratrol, it was found that resveratrol has more significant cytotoxicity in cancer cell lines. Resveratrol could play a toxic role through inducing apoptosis of the cancer cell in a time- and concentration-dependent manner. A total of 330 significantly differential genes were identified through large-scale transcriptome sequencing, among which 103 genes were upregulated and 227 genes were downregulated. Transcriptome and qRT-PCR data proved that a large number of genes related to cell cycle were differentially expressed after the treatment of resveratrol. The changes of cell cycle phases at different time points after treating with resveratrol were further detected, and it was found that the cells were arrested in the S phase because of the percentage of cells in S phase increased and cells in G1/G0 phase decreased. In conclusion, resveratrol can inhibit the proliferation of 4T1 cancer cells by inhibiting cell cycle and inducing apoptosis. Full article

(This article belongs to the Special Issue Basic Research for the Potential Use of Plant Toxins)

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20 pages, 2472 KiB

Open AccessEditor’s ChoiceArticle

Ciguatoxin Occurrence in Food-Web Components of a Cuban Coral Reef Ecosystem: Risk-Assessment Implications

by Lisbet Díaz-Asencio, Rachel J. Clausing, Mark Vandersea, Donaida Chamero-Lago, Miguel Gómez-Batista, Joan I. Hernández-Albernas, Nicolas Chomérat, Gabriel Rojas-Abrahantes, R. Wayne Litaker, Patricia Tester, Jorge Diogène, Carlos M. Alonso-Hernández and Marie-Yasmine Dechraoui Bottein

Toxins 2019, 11(12), 722; https://doi.org/10.3390/toxins11120722 - 11 Dec 2019

Cited by 34 | Viewed by 5366

Abstract

In Cuba, ciguatera poisoning associated with fish consumption is the most commonly occurring non-bacterial seafood-borne illness. Risk management through fish market regulation has existed in Cuba for decades and consists of bans on selected species above a certain weight; however, the actual occurrence [...] Read more.

In Cuba, ciguatera poisoning associated with fish consumption is the most commonly occurring non-bacterial seafood-borne illness. Risk management through fish market regulation has existed in Cuba for decades and consists of bans on selected species above a certain weight; however, the actual occurrence of ciguatoxins (CTXs) in seafood has never been verified. From this food safety risk management perspective, a study site locally known to be at risk for ciguatera was selected. Analysis of the epiphytic dinoflagellate community identified the microalga Gambierdiscus. Gambierdiscus species included six of the seven species known to be present in Cuba (G. caribaeus, G. belizeanus, G. carpenteri, G. carolinianus, G. silvae, and F. ruetzleri). CTX-like activity in invertebrates, herbivorous and carnivorous fishes were analyzed with a radioligand receptor-binding assay and, for selected samples, with the N2A cell cytotoxicity assay. CTX activity was found in 80% of the organisms sampled, with toxin values ranging from 2 to 8 ng CTX3C equivalents g⁻¹ tissue. Data analysis further confirmed CTXs trophic magnification. This study constitutes the first finding of CTX-like activity in marine organisms in Cuba and in herbivorous fish in the Caribbean. Elucidating the structure–activity relationship and toxicology of CTX from the Caribbean is needed before conclusions may be drawn about risk exposure in Cuba and the wider Caribbean. Full article

(This article belongs to the Special Issue Marine Toxins Detection)

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22 pages, 2633 KiB

Open AccessEditor’s ChoiceArticle

Analysis of Pyrrolizidine Alkaloids in Queensland Honey: Using Low Temperature Chromatography to Resolve Stereoisomers and Identify Botanical Sources by UHPLC-MS/MS

by Natasha L. Hungerford, Steve J. Carter, Shalona R. Anuj, Benjamin L. L. Tan, Darina Hnatko, Christopher L. Martin, Elipsha Sharma, Mukan Yin, Thao T. P. Nguyen, Kevin J. Melksham and Mary T. Fletcher

Toxins 2019, 11(12), 726; https://doi.org/10.3390/toxins11120726 - 11 Dec 2019

Cited by 26 | Viewed by 5642

Abstract

Pyrrolizidine alkaloids (PAs) are a diverse group of plant secondary metabolites with known varied toxicity. Consumption of 1,2-unsaturated PAs has been linked to acute and chronic liver damage, carcinogenicity and death, in livestock and humans, making their presence in food of concern to [...] Read more.

Pyrrolizidine alkaloids (PAs) are a diverse group of plant secondary metabolites with known varied toxicity. Consumption of 1,2-unsaturated PAs has been linked to acute and chronic liver damage, carcinogenicity and death, in livestock and humans, making their presence in food of concern to food regulators in Australia and internationally. In this survey, honey samples sourced from markets and shops in Queensland (Australia), were analysed by high-resolution Orbitrap UHPLC-MS/MS for 30 common PAs. Relationships between the occurrence of pyrrolizidine alkaloids and the botanical origin of the honey are essential as pyrrolizidine alkaloid contamination at up to 3300 ng/g were detected. In this study, the predominant alkaloids detected were isomeric PAs, lycopsamine, indicine and intermedine, exhibiting identical MS/MS spectra, along with lesser amounts of each of their N-oxides. Crucially, chromatographic UHPLC conditions were optimised by operation at low temperature (5 °C) to resolve these key isomeric PAs. Such separation of these isomers by UHPLC, enabled the relative proportions of these PAs present in honey to be compared to alkaloid levels in suspect source plants. Overall plant pyrrolizidine alkaloid profiles were compared to those found in honey samples to help identify the most important plants responsible for honey contamination. The native Australian vines of Parsonsia spp. are proposed as a likely contributor to high levels of lycopsamine in many of the honeys surveyed. Botanical origin information such as this, gained via low temperature chromatographic resolution of isomeric PAs, will be very valuable in identifying region of origin for honey samples. Full article

(This article belongs to the Special Issue Improved Analytical Technologies for the Detection of Natural Toxins and Their Metabolites in Food)

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16 pages, 1362 KiB

Open AccessEditor’s ChoiceArticle

The Effect of a Combined Hydrogen Peroxide-MlrA Treatment on the Phytoplankton Community and Microcystin Concentrations in a Mesocosm Experiment in Lake Ludoš

by Dariusz Dziga, Nada Tokodi, Damjana Drobac, Mikołaj Kokociński, Adam Antosiak, Jakub Puchalski, Wojciech Strzałka, Mariusz Madej, Zorica Svirčev and Jussi Meriluoto

Toxins 2019, 11(12), 725; https://doi.org/10.3390/toxins11120725 - 11 Dec 2019

Cited by 24 | Viewed by 3830

Abstract

Harmful cyanobacteria and their toxic metabolites constitute a big challenge for the production of safe drinking water. Microcystins (MC), chemically stable hepatotoxic heptapeptides, have often been involved in cyanobacterial poisoning incidents. A desirable solution for cyanobacterial management in lakes and ponds would eliminate [...] Read more.

Harmful cyanobacteria and their toxic metabolites constitute a big challenge for the production of safe drinking water. Microcystins (MC), chemically stable hepatotoxic heptapeptides, have often been involved in cyanobacterial poisoning incidents. A desirable solution for cyanobacterial management in lakes and ponds would eliminate both excess cyanobacteria and the MC that they potentially produce and release upon lysis. Hydrogen peroxide (H₂O₂) has recently been advocated as an efficient means of lysing cyanobacteria in lakes and ponds, however H₂O₂ (at least when used at typical concentrations) cannot degrade MC in environmental waters. Therefore, mesocosm experiments combining the cyanobacteria-lysing effect of H₂O₂ and the MC-degrading capacity of the enzyme MlrA were set up in the highly eutrophic Lake Ludoš (Serbia). The H₂O₂ treatment decreased the abundance of the dominant cyanobacterial taxa Limnothrix sp., Aphanizomenon flos-aquae, and Planktothrix agardhii. The intracellular concentration of MC was reduced/eliminated by H₂O₂, yet the reduction of the extracellular MC could only be accomplished by supplementation with MlrA. However, as H₂O₂ was found to induce the expression of mcyB and mcyE genes, which are involved in MC biosynthesis, the use of H₂O₂ as a safe cyanobacteriocide still requires further investigation. In conclusion, the experiments showed that the combined use of H₂O₂ and MlrA is promising in the elimination of both excess cyanobacteria and their MC in environmental waters. Full article

(This article belongs to the Special Issue Human Exposure to Freshwater Toxins: Assessment, Potential, Consequences and Prevention)

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17 pages, 4111 KiB

Open AccessEditor’s ChoiceArticle

Co-Occurrence of DON and Emerging Mycotoxins in Worldwide Finished Pig Feed and Their Combined Toxicity in Intestinal Cells

by Abdullah Khan Khoshal, Barbara Novak, Pascal G. P. Martin, Timothy Jenkins, Manon Neves, Gerd Schatzmayr, Isabelle P. Oswald and Philippe Pinton

Toxins 2019, 11(12), 727; https://doi.org/10.3390/toxins11120727 - 11 Dec 2019

Cited by 61 | Viewed by 6109

Abstract

Food and feed can be naturally contaminated by several mycotoxins, and concern about the hazard of exposure to mycotoxin mixtures is increasing. In this study, more than 800 metabolites were analyzed in 524 finished pig feed samples collected worldwide. Eighty-eight percent of the [...] Read more.

Food and feed can be naturally contaminated by several mycotoxins, and concern about the hazard of exposure to mycotoxin mixtures is increasing. In this study, more than 800 metabolites were analyzed in 524 finished pig feed samples collected worldwide. Eighty-eight percent of the samples were co-contaminated with deoxynivalenol (DON) and other regulated/emerging mycotoxins. The Top 60 emerging/regulated mycotoxins co-occurring with DON in pig feed shows that 48%, 13%, 8% and 12% are produced by Fusarium, Aspergillus, Penicillium and Alternaria species, respectively. Then, the individual and combined toxicity of DON and the 10 most prevalent emerging mycotoxins (brevianamide F, cyclo-(L-Pro-L-Tyr), tryptophol, enniatins A1, B, B1, emodin, aurofusarin, beauvericin and apicidin) was measured at three ratios corresponding to pig feed contamination. Toxicity was assessed by measuring the viability of intestinal porcine epithelial cells, IPEC-1, at 48-h. BRV-F, Cyclo and TRPT did not alter cell viability. The other metabolites were ranked in the following order of toxicity: apicidin > enniatin A1 > DON > beauvericin > enniatin B > enniatin B1 > emodin > aurofusarin. In most of the mixtures, combined toxicity was similar to the toxicity of DON alone. In terms of pig health, these results demonstrate that the co-occurrence of emerging mycotoxins that we tested with DON does not exacerbate toxicity. Full article

(This article belongs to the Special Issue Mycotoxins Occurence in Feed and Their Influence on Animal Health)

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18 pages, 4714 KiB

Open AccessEditor’s ChoiceArticle

Regulation of Morphology, Aflatoxin Production, and Virulence of Aspergillus flavus by the Major Nitrogen Regulatory Gene areA

by Opemipo Esther Fasoyin, Kunlong Yang, Mengguang Qiu, Bin Wang, Sen Wang and Shihua Wang

Toxins 2019, 11(12), 718; https://doi.org/10.3390/toxins11120718 - 10 Dec 2019

Cited by 29 | Viewed by 4368

Abstract

Aspergillus flavus is a renowned plant, animal and human pathogen. areA is a global nitrogen regulatory gene of the GATA transcription factor family, shown to be the major nitrogen regulator. In this study, we identified areA in A. flavus and studied its function. [...] Read more.

Aspergillus flavus is a renowned plant, animal and human pathogen. areA is a global nitrogen regulatory gene of the GATA transcription factor family, shown to be the major nitrogen regulator. In this study, we identified areA in A. flavus and studied its function. The AreA protein contained a signatory zinc finger domain, which is extremely conserved across fungal species. Gene deletion (ΔareA) and over-expression (OE::areA) strains were constructed by homologous recombination to elucidate the role of areA in A. flavus. The ΔareA strain was unable to efficiently utilize secondary nitrogen sources for growth of A. flavus, and it had poorly developed conidiophores, when observed on complete medium, resulting in the production of significantly less conidia than the wild-type strain (WT). Aflatoxin B1 (AFB1) production was reduced in ΔareA compared with the WT strain in most conditions tested, and ΔareA had impaired virulence in peanut seeds. areA also played important roles in the sensitivity of A. flavus to osmotic, cell wall and oxidative stresses. Hence, areA was found to be important for the growth, aflatoxin production and pathogenicity of A. flavus. This work sheds light on the function of areA in the regulation of the nitrogen metabolism of A. flavus, and consequently aims at providing new ways for controlling the crossover pathogen, A. flavus. Full article

(This article belongs to the Special Issue Aflatoxins: Food Sources, Occurrence and Toxicological Effects)

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20 pages, 2442 KiB

Open AccessEditor’s ChoiceArticle

Proteo-Transcriptomic Characterization of the Venom from the Endoparasitoid Wasp Pimpla turionellae with Aspects on Its Biology and Evolution

by Rabia Özbek, Natalie Wielsch, Heiko Vogel, Günter Lochnit, Frank Foerster, Andreas Vilcinskas and Björn Marcus von Reumont

Toxins 2019, 11(12), 721; https://doi.org/10.3390/toxins11120721 - 10 Dec 2019

Cited by 20 | Viewed by 6737

Abstract

Within mega-diverse Hymenoptera, non-aculeate parasitic wasps represent 75% of all hymenopteran species. Their ovipositor dual-functionally injects venom and employs eggs into (endoparasitoids) or onto (ectoparasitoids) diverse host species. Few endoparasitoid wasps such as Pimpla turionellae paralyze the host and suppress its immune responses, [...] Read more.

Within mega-diverse Hymenoptera, non-aculeate parasitic wasps represent 75% of all hymenopteran species. Their ovipositor dual-functionally injects venom and employs eggs into (endoparasitoids) or onto (ectoparasitoids) diverse host species. Few endoparasitoid wasps such as Pimpla turionellae paralyze the host and suppress its immune responses, such as encapsulation and melanization, to guarantee their offspring’s survival. Here, the venom and its possible biology and function of P. turionellae are characterized in comparison to the few existing proteo-transcriptomic analyses on parasitoid wasp venoms. Multiple transcriptome assembly and custom-tailored search and annotation strategies were applied to identify parasitoid venom proteins. To avoid false-positive hits, only transcripts were finally discussed that survived strict filter settings, including the presence in the proteome and higher expression in the venom gland. P. turionella features a venom that is mostly composed of known, typical parasitoid enzymes, cysteine-rich peptides, and other proteins and peptides. Several venom proteins were identified and named, such as pimplin2, 3, and 4. However, the specification of many novel candidates remains difficult, and annotations ambiguous. Interestingly, we do not find pimplin, a paralytic factor in Pimpla hypochondriaca, but instead a new cysteine inhibitor knot (ICK) family (pimplin2), which is highly similar to known, neurotoxic asilid1 sequences from robber flies. Full article

(This article belongs to the Section Animal Venoms)

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15 pages, 325 KiB

Open AccessEditor’s ChoiceArticle

Selected Trichothecenes in Barley Malt and Beer from Poland and an Assessment of Dietary Risks Associated with their Consumption

by Edyta Ksieniewicz-Woźniak, Marcin Bryła, Agnieszka Waśkiewicz, Tomoya Yoshinari and Krystyna Szymczyk

Toxins 2019, 11(12), 715; https://doi.org/10.3390/toxins11120715 - 9 Dec 2019

Cited by 24 | Viewed by 3686

Abstract

Eighty-seven samples of malt from several Polish malting plants and 157 beer samples from the beer available on the Polish market (in 2018) were tested for Fusarium mycotoxins (deoxynivalenol (DON), nivalenol (NIV)), and their modified forms ((deoxynivalenol-3-glucoside (DON-3G), nivalenol-3-glucoside (NIV-3G), 3-acetyldeoxynivalenol (3-AcDON)). DON [...] Read more.

Eighty-seven samples of malt from several Polish malting plants and 157 beer samples from the beer available on the Polish market (in 2018) were tested for Fusarium mycotoxins (deoxynivalenol (DON), nivalenol (NIV)), and their modified forms ((deoxynivalenol-3-glucoside (DON-3G), nivalenol-3-glucoside (NIV-3G), 3-acetyldeoxynivalenol (3-AcDON)). DON and its metabolite, DON-3G, were found the most, among the samples analyzed; DON and DON-3G were present in 90% and 91% of malt samples, and in 97% and 99% of beer samples, respectively. NIV was found in 24% of malt samples and in 64% of beer samples, and NIV-3G was found in 48% of malt samples and 39% of beer samples. In the malt samples, the mean concentration of DON was 52.9 µg/kg (range: 5.3–347.6 µg/kg) and that of DON-3G was 74.1 µg/kg (range: 4.4–410.3 µg/kg). In the beer samples, the mean concentration of DON was 12.3 µg/L (range: 1.2–156.5 µg/L) and that of DON-3G was 7.1 µg/L (range: 0.6–58.4 µg/L). The concentrations of other tested mycotoxins in the samples of malt and beer were several times lower. The risk of exposure to the tested mycotoxins, following the consumption of beer in Poland, was assessed. The corresponding probable daily intakes (PDIs) remained a small fraction of the tolerable daily intake (TDI). However, in the improbable worst-case scenario, in which every beer bottle consumed would be contaminated with mycotoxins present at the highest level observed among the analyzed beer samples, the PDI would exceed the TDI for DON and its metabolite after the consumption of a single bottle (0.5 L) of beer. Full article

(This article belongs to the Special Issue Fate of Free, “Masked” and Conjugated/Modified forms of Mycotoxins)

14 pages, 281 KiB

Open AccessEditor’s ChoiceArticle

Knowledge, Attitude and Practice of Malawian Farmers on Pre- and Post-Harvest Crop Management to Mitigate Aflatoxin Contamination in Groundnut, Maize and Sorghum—Implication for Behavioral Change

by Seetha Anitha, Takuji W. Tsusaka, Samuel M.C. Njoroge, Nelson Kumwenda, Lizzie Kachulu, Joseph Maruwo, Norah Machinjiri, Rosemary Botha, Harry W. Msere, Juma Masumba, Angela Tavares, Geoffrey M Heinrich, Moses Siambi and Patrick Okori

Toxins 2019, 11(12), 716; https://doi.org/10.3390/toxins11120716 - 9 Dec 2019

Cited by 29 | Viewed by 6056

Abstract

A knowledge, attitude and practice (KAP) study was conducted in three districts of Malawi to test whether the training had resulted in increased knowledge and adoption of recommended pre- and post-harvest crop management practices, and their contribution to reducing aflatoxin contamination in groundnut, [...] Read more.

A knowledge, attitude and practice (KAP) study was conducted in three districts of Malawi to test whether the training had resulted in increased knowledge and adoption of recommended pre- and post-harvest crop management practices, and their contribution to reducing aflatoxin contamination in groundnut, maize and sorghum. The study was conducted with 900 farmers at the baseline and 624 farmers at the end-line, while 726 and 696 harvested crop samples were collected for aflatoxin testing at the baseline and end-line, respectively. Results show that the knowledge and practice of pre- and post-harvest crop management for mitigating aflatoxin were inadequate among the farmers at the baseline but somewhat improved after the training as shown at the end-line. As a result, despite unfavorable weather, the mean aflatoxin contamination level in their grain samples decreased from 83.6 to 55.8 ppb (p < 0.001). However, it was also noted that increased knowledge did not significantly change farmers’ attitude toward not consuming grade-outs because of economic incentive incompatibility, leaving potential for improving the practices further. This existing gap in the adoption of aflatoxin mitigation practices calls for approaches that take into account farmers’ needs and incentives to attain sustainable behavioral change. Full article

(This article belongs to the Special Issue Mycotoxins in Food: Origin and Management of Risk)

14 pages, 4810 KiB

Open AccessEditor’s ChoiceArticle

PirAB^VP Toxin Binds to Epithelial Cells of the Digestive Tract and Produce Pathognomonic AHPND Lesions in Germ-Free Brine Shrimp

by Vikash Kumar, Lobke De Bels, Liesbeth Couck, Kartik Baruah, Peter Bossier and Wim Van den Broeck

Toxins 2019, 11(12), 717; https://doi.org/10.3390/toxins11120717 - 9 Dec 2019

Cited by 37 | Viewed by 6105

Abstract

Acute hepatopancreatic necrosis disease (AHPND), a newly emergent farmed penaeid shrimp bacterial disease originally known as early mortality syndrome (EMS), is causing havoc in the shrimp industry. The causative agent of AHPND was found to be a specific strain of bacteria, e.g., Vibrio [...] Read more.

Acute hepatopancreatic necrosis disease (AHPND), a newly emergent farmed penaeid shrimp bacterial disease originally known as early mortality syndrome (EMS), is causing havoc in the shrimp industry. The causative agent of AHPND was found to be a specific strain of bacteria, e.g., Vibrio and Shewanella sps., that contains pVA1 plasmid (63–70 kb) encoding the binary PirA^VP and PirB^VP toxins. The PirAB^VP and toxins are the primary virulence factors of AHPND-causing bacteria that mediates AHPND and mortality in shrimp. Hence, in this study using a germ-free brine shrimp model system, we evaluated the PirAB^VP toxin-mediated infection process at cellular level, including toxin attachment and subsequent toxin-induced damage to the digestive tract. The results showed that, PirAB^VP toxin binds to epithelial cells of the digestive tract of brine shrimp larvae and produces characteristic symptoms of AHPND. In the PirAB^VP-challenged brine shrimp larvae, shedding or sloughing of enterocytes in the midgut and hindgut regions was regularly visualized, and the intestinal lumen was filled with moderately electron-dense cells of variable shapes and sizes. In addition, the observed cellular debris in the intestinal lumen of the digestive tract was found to be of epithelial cell origin. The detailed morphology of the digestive tract demonstrates further that the PirAB^VP toxin challenge produces focal to extensive necrosis and damages epithelial cells in the midgut and hindgut regions, resulting in pyknosis, cell vacuolisation, and mitochondrial and rough endoplasmic reticulum (RER) damage to different degrees. Taken together, our study provides substantial evidence that PirAB^VP toxins bind to the digestive tract of brine shrimp larvae and seem to be responsible for generating characteristic AHPND lesions and damaging enterocytes in the midgut and hindgut regions. Full article

(This article belongs to the Section Bacterial Toxins)

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40 pages, 2280 KiB

Open AccessEditor’s ChoiceReview

Structural Diversity, Characterization and Toxicology of Microcystins

by Noureddine Bouaïcha, Christopher O. Miles, Daniel G. Beach, Zineb Labidi, Amina Djabri, Naila Yasmine Benayache and Tri Nguyen-Quang

Toxins 2019, 11(12), 714; https://doi.org/10.3390/toxins11120714 - 7 Dec 2019

Cited by 340 | Viewed by 14079

Abstract

Hepatotoxic microcystins (MCs) are the most widespread class of cyanotoxins and the one that has most often been implicated in cyanobacterial toxicosis. One of the main challenges in studying and monitoring MCs is the great structural diversity within the class. The full chemical [...] Read more.

Hepatotoxic microcystins (MCs) are the most widespread class of cyanotoxins and the one that has most often been implicated in cyanobacterial toxicosis. One of the main challenges in studying and monitoring MCs is the great structural diversity within the class. The full chemical structure of the first MC was elucidated in the early 1980s and since then, the number of reported structural analogues has grown steadily and continues to do so, thanks largely to advances in analytical methodology. The structures of some of these analogues have been definitively elucidated after chemical isolation using a combination of techniques including nuclear magnetic resonance, amino acid analysis, and tandem mass spectrometry (MS/MS). Others have only been tentatively identified using liquid chromatography-MS/MS without chemical isolation. An understanding of the structural diversity of MCs, the genetic and environmental controls for this diversity and the impact of structure on toxicity are all essential to the ongoing study of MCs across several scientific disciplines. However, because of the diversity of MCs and the range of approaches that have been taken for characterizing them, comprehensive information on the state of knowledge in each of these areas can be challenging to gather. We have conducted an in-depth review of the literature surrounding the identification and toxicity of known MCs and present here a concise review of these topics. At present, at least 279 MCs have been reported and are tabulated here. Among these, about 20% (55 of 279) appear to be the result of chemical or biochemical transformations of MCs that can occur in the environment or during sample handling and extraction of cyanobacteria, including oxidation products, methyl esters, or post-biosynthetic metabolites. The toxicity of many MCs has also been studied using a range of different approaches and a great deal of variability can be observed between reported toxicities, even for the same congener. This review will help clarify the current state of knowledge on the structural diversity of MCs as a class and the impacts of structure on toxicity, as well as to identify gaps in knowledge that should be addressed in future research. Full article

(This article belongs to the Special Issue Cyanobacterial Toxins: Identification and Structural Characterisation to Better Understand Their Distribution and Diversity)

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14 pages, 306 KiB

Open AccessEditor’s ChoiceArticle

Coevolution of Snake Venom Toxic Activities and Diet: Evidence that Ecological Generalism Favours Toxicological Diversity

by Emma-Louise Davies and Kevin Arbuckle

Toxins 2019, 11(12), 711; https://doi.org/10.3390/toxins11120711 - 6 Dec 2019

Cited by 50 | Viewed by 8040

Abstract

Snake venom evolution is typically considered to be predominantly driven by diet-related selection pressures. Most evidence for this is based on lethality to prey and non-prey species and on the identification of prey specific toxins. Since the broad toxicological activities (e.g., neurotoxicity, coagulotoxicity, [...] Read more.

Snake venom evolution is typically considered to be predominantly driven by diet-related selection pressures. Most evidence for this is based on lethality to prey and non-prey species and on the identification of prey specific toxins. Since the broad toxicological activities (e.g., neurotoxicity, coagulotoxicity, etc.) sit at the interface between molecular toxinology and lethality, these classes of activity may act as a key mediator in coevolutionary interactions between snakes and their prey. Indeed, some recent work has suggested that variation in these functional activities may be related to diet as well, but previous studies have been limited in geographic and/or taxonomic scope. In this paper, we take a phylogenetic comparative approach to investigate relationships between diet and toxicological activity classes on a global scale across caenophidian snakes, using the clinically oriented database at toxinology.com. We generally find little support for specific prey types selecting for particular toxicological effects except that reptile-feeders are more likely to be neurotoxic. We find some support for endothermic prey (with higher metabolic rates) influencing toxic activities, but differently from previous suggestions in the literature. More broadly, we find strong support for a general effect of increased diversity of prey on the diversity of toxicological effects of snake venom. Hence, we provide evidence that selection pressures on the toxicological activities of snake venom has largely been driven by prey diversity rather than specific types of prey. These results complement and extend previous work to suggest that specific matching of venom characteristics to prey may occur at the molecular level and translate into venom lethality, but the functional link between those two is not constrained to a particular toxicological route. Full article

(This article belongs to the Special Issue Evolutionary Ecology of Venom)

25 pages, 1084 KiB

Open AccessEditor’s ChoiceReview

Botulinum Toxin Therapy Combined with Rehabilitation for Stroke: A Systematic Review of Effect on Motor Function

by Takatoshi Hara, Ryo Momosaki, Masachika Niimi, Naoki Yamada, Hiroyoshi Hara and Masahiro Abo

Toxins 2019, 11(12), 707; https://doi.org/10.3390/toxins11120707 - 5 Dec 2019

Cited by 34 | Viewed by 7906

Abstract

Aim: The purpose of this study was to examine the effectiveness of botulinum toxin A (BoNT-A) therapy combined with rehabilitation on motor function in post-stroke patients. Methods: The following sources up to December 31, 2018, were searched from inception for articles in English: [...] Read more.

Aim: The purpose of this study was to examine the effectiveness of botulinum toxin A (BoNT-A) therapy combined with rehabilitation on motor function in post-stroke patients. Methods: The following sources up to December 31, 2018, were searched from inception for articles in English: Pubmed, Scopus, CINAHL, Embase, PsycINFO, and CENTRAL. Trials using injections of BoNT-A for upper and lower limb rehabilitation were examined. We excluded studies that were not performed for rehabilitation or were not evaluated for motor function. Results: Twenty-six studies were included. In addition to rehabilitation, nine studies used adjuvant treatment to improve spasticity or improve motor function. In the upper limbs, two of 14 articles indicated that significant improvement in upper limb motor function was observed compared to the control group. In the lower limbs, seven of 14 articles indicated that significant improvement in lower limb motor function was observed compared to the control group. Conclusions: The effect of combined with rehabilitation is limited after stroke, and there is not sufficient evidence, but results suggest that BoNT-A may help to improve motor function. In future studies, the establishment of optimal rehabilitation and evaluation times of BoNT-A treatment will be necessary for improving motor function and spasticity. Full article

(This article belongs to the Special Issue Effects of Botulinum Toxin on Functional Recovery after Injuries of Nervous System)

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13 pages, 586 KiB

Open AccessEditor’s ChoiceArticle

Efficacy of the Combined Protective Cultures of Penicillium chrysogenum and Debaryomyces hansenii for the Control of Ochratoxin A Hazard in Dry-Cured Ham

by Eva Cebrián, Mar Rodríguez, Belén Peromingo, Elena Bermúdez and Félix Núñez

Toxins 2019, 11(12), 710; https://doi.org/10.3390/toxins11120710 - 5 Dec 2019

Cited by 38 | Viewed by 3810

Abstract

The ecological conditions during the ripening of dry-cured ham favour the development of moulds on its surface, being frequently the presence of Penicillium nordicum, a producer of ochratoxin A (OTA). Biocontrol using moulds and yeasts usually found in dry-cured ham is a [...] Read more.

The ecological conditions during the ripening of dry-cured ham favour the development of moulds on its surface, being frequently the presence of Penicillium nordicum, a producer of ochratoxin A (OTA). Biocontrol using moulds and yeasts usually found in dry-cured ham is a promising strategy to minimize this hazard. The aim of this work is to evaluate the effect of previously selected Debaryomyces hansenii and Penicillium chrysogenum strains on growth, OTA production, and relative expression of genes involved in the OTA biosynthesis by P. nordicum. P. nordicum was inoculated against the protective cultures individually and combined on dry-cured ham for 21 days at 20 °C. None of the treatments reduced the growth of P. nordicum, but all of them decreased OTA concentration. The lower production of OTA could be related to significant repression of the relative expression of otapksPN and otanpsPN genes of P. nordicum. The efficacy of the combined protective cultures was tested in 24 dry-cured hams in industrial ripening (an 8 month-long production). OTA was detected in nine of the 12 dry-cured hams in the batch inoculated only with P. nordicum. However, in the batch inoculated with both P. nordicum and the combined protective culture, a considerable reduction of OTA contamination was observed. In conclusion, although the efficacy of individual use P. chrysogenum is great, the combination with D. hansenii enhances its antifungal activity and could be proposed as a mixed protective culture to control the hazard of the presence of OTA in dry-cured ham. Full article

(This article belongs to the Special Issue Novel Approaches to Minimising Mycotoxin Contamination)

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19 pages, 790 KiB

Open AccessEditor’s ChoiceReview

Programmed Cell Death-Like and Accompanying Release of Microcystin in Freshwater Bloom-Forming Cyanobacterium Microcystis: From Identification to Ecological Relevance

by Chenlin Hu and Piotr Rzymski

Toxins 2019, 11(12), 706; https://doi.org/10.3390/toxins11120706 - 4 Dec 2019

Cited by 50 | Viewed by 10382

Abstract

Microcystis is the most common freshwater bloom-forming cyanobacterium. Its massive blooms not only adversely affect the functionality of aquatic ecosystems, but are also associated with the production of microcystins (MCs), a group of potent toxins that become a threat to public health when [...] Read more.

Microcystis is the most common freshwater bloom-forming cyanobacterium. Its massive blooms not only adversely affect the functionality of aquatic ecosystems, but are also associated with the production of microcystins (MCs), a group of potent toxins that become a threat to public health when cell-bound MCs are significantly released from the dying Microcystis into the water column. Managing Microcystis blooms thus requires sufficient knowledge regarding both the cell death modes and the release of toxins. Recently, more and more studies have demonstrated the occurrence of programmed cell death-like (or apoptosis-like) events in laboratory and field samples of Microcystis. Apoptosis is a genetically controlled process that is essential for the development and survival of metazoa; however, it has been gradually realized to be an existing phenomenon playing important ecological roles in unicellular microorganisms. Here, we review the current progress and the existing knowledge gap regarding apoptosis-like death in Microcystis. Specifically, we focus first on the tools utilized to characterize the apoptosis-related biochemical and morphological features in Microcystis. We further outline various stressful stimuli that trigger the occurrence of apoptosis and discuss the potential mechanisms of apoptosis in Microcystis. We then propose a conceptual model to describe the functional coupling of apoptosis and MC in Microcystis. This model could be useful for understanding both roles of MC and apoptosis in this species. Lastly, we conclude the review by highlighting the current knowledge gap and considering the direction of future research. Overall, this review provides a recent update with respect to the knowledge of apoptosis in Microcystis and also offers a guide for future investigations of its ecology and survival strategies. Full article

(This article belongs to the Special Issue Biological Role of Cyanotoxins: Experimental and In-Field Evidence)

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12 pages, 2025 KiB

Open AccessEditor’s ChoiceArticle

In-Vitro Application of a Qatari Burkholderia cepacia strain (QBC03) in the Biocontrol of Mycotoxigenic Fungi and in the Reduction of Ochratoxin A biosynthesis by Aspergillus carbonarius

by Randa Zeidan, Zahoor Ul-Hassan, Roda Al-Thani, Quirico Migheli and Samir Jaoua

Toxins 2019, 11(12), 700; https://doi.org/10.3390/toxins11120700 - 2 Dec 2019

Cited by 22 | Viewed by 4226

Abstract

Mycotoxins are secondary metabolites produced by certain filamentous fungi, causing human and animal health issues upon the ingestion of contaminated food and feed. Among the safest approaches to the control of mycotoxigenic fungi and mycotoxin detoxification is the application of microbial biocontrol agents. [...] Read more.

Mycotoxins are secondary metabolites produced by certain filamentous fungi, causing human and animal health issues upon the ingestion of contaminated food and feed. Among the safest approaches to the control of mycotoxigenic fungi and mycotoxin detoxification is the application of microbial biocontrol agents. Burkholderia cepacia is known for producing metabolites active against a broad number of pathogenic fungi. In this study, the antifungal potential of a Qatari strain of Burkholderia cepacia (QBC03) was explored. QBC03 exhibited antifungal activity against a wide range of mycotoxigenic, as well as phytopathogenic, fungal genera and species. The QBC03 culture supernatant significantly inhibited the growth of Aspergillus carbonarius, Fusarium culmorum and Penicillium verrucosum in PDA medium, as well as A. carbonarius and P. verrucosum biomass in PDB medium. The QBC03 culture supernatant was found to dramatically reduce the synthesis of ochratoxin A (OTA) by A. carbonarius, in addition to inducing mycelia malformation. The antifungal activity of QBC03’s culture extract was retained following thermal treatment at 100 °C for 30 min. The findings of the present study advocate that QBC03 is a suitable biocontrol agent against toxigenic fungi, due to the inhibitory activity of its thermostable metabolites. Full article

(This article belongs to the Special Issue Biocontrol Agents and Natural Compounds against Mycotoxinogenic Fungi)

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18 pages, 389 KiB

Open AccessEditor’s ChoiceReview

Use of Competitive Filamentous Fungi as an Alternative Approach for Mycotoxin Risk Reduction in Staple Cereals: State of Art and Future Perspectives

by Sabrina Sarrocco, Antonio Mauro and Paola Battilani

Toxins 2019, 11(12), 701; https://doi.org/10.3390/toxins11120701 - 2 Dec 2019

Cited by 63 | Viewed by 6076

Abstract

Among plant fungal diseases, those affecting cereals represent a huge problem in terms of food security and safety. Cereals, such as maize and wheat, are very often targets of mycotoxigenic fungi. The limited availability of chemical plant protection products and physical methods to [...] Read more.

Among plant fungal diseases, those affecting cereals represent a huge problem in terms of food security and safety. Cereals, such as maize and wheat, are very often targets of mycotoxigenic fungi. The limited availability of chemical plant protection products and physical methods to control mycotoxigenic fungi and to reduce food and feed mycotoxin contamination fosters alternative approaches, such as the use of beneficial fungi as an active ingredient of biological control products. Competitive interactions, including both exploitation and interference competition, between pathogenic and beneficial fungi, are generally recognized as mechanisms to control plant pathogens populations and to manage plant diseases. In the present review, two examples concerning the use of competitive beneficial filamentous fungi for the management of cereal diseases are discussed. The authors retrace the history of the well-established use of non-aflatoxigenic isolates of Aspergillus flavus to prevent aflatoxin contamination in maize and give an overview of the potential use of competitive beneficial filamentous fungi to manage Fusarium Head Blight on wheat and mitigate fusaria toxin contamination. Although important steps have been made towards the development of microorganisms as active ingredients of plant protection products, a reasoned revision of the registration rules is needed to significantly reduce the chemical based plant protection products in agriculture. Full article

(This article belongs to the Collection Strategies to Minimising Mycotoxin Contamination in Foods and Feeds)

11 pages, 1462 KiB

Open AccessEditor’s ChoiceArticle

The Latoia consocia Caterpillar Induces Pain by Targeting Nociceptive Ion Channel TRPV1

by Zhihao Yao, Peter Muiruri Kamau, Yalan Han, Jingmei Hu, Anna Luo, Lei Luo, Jie Zheng, Yuhua Tian and Ren Lai

Toxins 2019, 11(12), 695; https://doi.org/10.3390/toxins11120695 - 27 Nov 2019

Cited by 15 | Viewed by 4907

Abstract

Accidental contact with caterpillar bristles causes local symptoms such as severe pain, intense heat, edema, erythema, and pruritus. However, there is little functional evidence to indicate a potential mechanism. In this study, we analyzed the biological characteristics of the crude venom from the [...] Read more.

Accidental contact with caterpillar bristles causes local symptoms such as severe pain, intense heat, edema, erythema, and pruritus. However, there is little functional evidence to indicate a potential mechanism. In this study, we analyzed the biological characteristics of the crude venom from the larval stage of Latoia consocia living in South-West China. Intraplantar injection of the venom into the hind paws of mice induced severe acute pain behaviors in wild type (WT) mice; the responses were much reduced in TRPV1-deficit (TRPV1 KO) mice. The TRPV1-specific inhibitor, capsazepine, significantly attenuated the pain behaviors. Furthermore, the crude venom evoked strong calcium signals in the dorsal root ganglion (DRG) neurons of WT mice but not those of TRPV1 KO mice. Among the pain-related ion channels we tested, the crude venom only activated the TRPV1 channel. To better understand the venom components, we analyzed the transcriptome of the L. consocia sebaceous gland region. Our study suggests that TRPV1 serves as a primary nociceptor in caterpillar-induced pain and forms the foundation for elucidating the pain-producing mechanism. Full article

(This article belongs to the Special Issue Animal Venoms and Their Components: Molecular Mechanisms of Action)

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12 pages, 1491 KiB

Open AccessEditor’s ChoiceArticle

High Specific Efficiency of Venom of Two Prey-Specialized Spiders

by Ondřej Michálek, Lucia Kuhn-Nentwig and Stano Pekár

Toxins 2019, 11(12), 687; https://doi.org/10.3390/toxins11120687 - 23 Nov 2019

Cited by 26 | Viewed by 6914

Abstract

The venom of predators should be under strong selection pressure because it is a costly substance and prey may potentially become resistant. Particularly in prey-specialized predators, venom should be selected for its high efficiency against the focal prey. Very effective venom paralysis has [...] Read more.

The venom of predators should be under strong selection pressure because it is a costly substance and prey may potentially become resistant. Particularly in prey-specialized predators, venom should be selected for its high efficiency against the focal prey. Very effective venom paralysis has been observed in specialized predators, such as spiders preying on dangerous prey. Here, we compared the toxicity of the venoms of two prey-specialized species, araneophagous Palpimanus sp. and myrmecophagous Zodarion nitidum, and their related generalist species. We injected different venom concentrations into two prey types—the prey preferred by a specialist and an alternative prey—and observed the mortality and the paralysis of the prey within 24 h. We found that the venoms of specialists were far more potent towards the preferred prey than alternative prey. The venoms of generalists were similarly potent towards both prey types. In addition, we tested the efficacy of two venom fractions (smaller and larger than 10 kDa) in araneophagous Palpimanus sp. Compounds larger than 10 kDa paralyzed both prey types, but smaller compounds (<10 kDa) were effective only on preferred prey, suggesting the presence of prey-specific compounds in the latter fraction. Our results confirm that prey-specialized spiders possess highly specific venom that allows them to subdue dangerous prey. Full article

(This article belongs to the Special Issue Evolutionary Ecology of Venom)

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12 pages, 704 KiB

Open AccessEditor’s ChoiceArticle

Mycotoxin Dietary Exposure Assessment through Fruit Juices Consumption in Children and Adult Population

by Noelia Pallarés, Dionisia Carballo, Emilia Ferrer, Mónica Fernández-Franzón and Houda Berrada

Toxins 2019, 11(12), 684; https://doi.org/10.3390/toxins11120684 - 22 Nov 2019

Cited by 29 | Viewed by 5190

Abstract

Consumption of fruit juice is becoming trendy for consumers seeking freshness and high vitamin and low caloric intake. Mycotoxigenic moulds may infect fruits during crop growth, harvest, and storage leading to mycotoxin production. Many mycotoxins are resistant to food processing, which make their [...] Read more.

Consumption of fruit juice is becoming trendy for consumers seeking freshness and high vitamin and low caloric intake. Mycotoxigenic moulds may infect fruits during crop growth, harvest, and storage leading to mycotoxin production. Many mycotoxins are resistant to food processing, which make their presence in the final juice product very likely expected. In this way, the presence of 30 mycotoxins including aflatoxin B1 (AFB1), aflatoxin B2 (AFB2), aflatoxin G1 (AFG1), aflatoxin G2 (AFG2), alternariol (AOH), alternariol monomethyl ether (AME), Ochratoxin A (OTA), fumonisin B1 (FB1), fumonisin B2 (FB2), enniatin A (ENNA), enniatin A1 (ENNA1), enniatin B (ENNB), enniatin B1 (ENNB1), beauvericin (BEA), sterigmatocystin (STG), zearalenone (ZEA), α-zearalanol (α-ZAL), β-zearalanol (β-ZAL), α-zearalenol (α-ZOL), β-zearalenol (β-ZOL), deoxynivalenol (DON), 3-acetyl-deoxynivalenol (3-ADON), 15-acetyl-deoxynivalenol (15-ADON), diacetoxyscirpenol (DAS), nivalenol (NIV), fusarenon-X (FUS-X), neosolaniol (NEO), patulin (PAT), T-2 toxin and HT-2 toxin was evaluated in 80 juice samples collected from Valencia retail Market. An efficient Dispersive Liquid-Liquid Microextraction method (DLLME) was carried out before their trace level determination by chromatographic techniques coupled to tandem mass spectrometry. The results obtained revealed the presence of nine mycotoxins namely AOH, AME, PAT, OTA, AFB1, AFB2, AFG2, β-ZAL, and HT2 in the analyzed samples, with incidences ranging from 3 to 29% and mean contents between 0.14 and 59.52 µg/L. Considerable percentages of TDIs were reached by children when 200 mL was considered as daily fruit juice intake. Full article

(This article belongs to the Special Issue Mycotoxins in Food: Origin and Management of Risk)

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12 pages, 311 KiB

Open AccessEditor’s ChoiceReview

Tables of Toxicity of Botulinum and Tetanus Neurotoxins

by Ornella Rossetto and Cesare Montecucco

Toxins 2019, 11(12), 686; https://doi.org/10.3390/toxins11120686 - 22 Nov 2019

Cited by 87 | Viewed by 12853

Abstract

Tetanus and botulinum neurotoxins are the most poisonous substances known, so much so as to be considered for a possible terrorist use. At the same time, botulinum neurotoxin type A1 is successfully used to treat a variety of human syndromes characterized by hyperactive [...] Read more.

Tetanus and botulinum neurotoxins are the most poisonous substances known, so much so as to be considered for a possible terrorist use. At the same time, botulinum neurotoxin type A1 is successfully used to treat a variety of human syndromes characterized by hyperactive cholinergic nerve terminals. The extreme toxicity of these neurotoxins is due to their neurospecificity and to their metalloprotease activity, which results in the deadly paralysis of tetanus and botulism. Recently, many novel botulinum neurotoxins and some botulinum-like toxins have been discovered. This large number of toxins differs in terms of toxicity and biological activity, providing a potential goldmine for novel therapeutics and for new molecular tools to dissect vesicular trafficking, fusion, and exocytosis. The scattered data on toxicity present in the literature require a systematic organization to be usable by scientists and clinicians. We have assembled here the data available in the literature on the toxicity of these toxins in different animal species. The internal comparison of these data provides insights on the biological activity of these toxins. Full article

(This article belongs to the Special Issue Characterization and Quantitative Analysis of Botulinum Neurotoxin)

26 pages, 374 KiB

Open AccessEditor’s ChoiceReview

Helicobacter pylori Virulence Factors Exploiting Gastric Colonization and its Pathogenicity

by Shamshul Ansari and Yoshio Yamaoka

Toxins 2019, 11(11), 677; https://doi.org/10.3390/toxins11110677 - 19 Nov 2019

Cited by 184 | Viewed by 18446

Abstract

Helicobacter pylori colonizes the gastric epithelial cells of at least half of the world’s population, and it is the strongest risk factor for developing gastric complications like chronic gastritis, ulcer diseases, and gastric cancer. To successfully colonize and establish a persistent infection, the [...] Read more.

Helicobacter pylori colonizes the gastric epithelial cells of at least half of the world’s population, and it is the strongest risk factor for developing gastric complications like chronic gastritis, ulcer diseases, and gastric cancer. To successfully colonize and establish a persistent infection, the bacteria must overcome harsh gastric conditions. H. pylori has a well-developed mechanism by which it can survive in a very acidic niche. Despite bacterial factors, gastric environmental factors and host genetic constituents together play a co-operative role for gastric pathogenicity. The virulence factors include bacterial colonization factors BabA, SabA, OipA, and HopQ, and the virulence factors necessary for gastric pathogenicity include the effector proteins like CagA, VacA, HtrA, and the outer membrane vesicles. Bacterial factors are considered more important. Here, we summarize the recent information to better understand several bacterial virulence factors and their role in the pathogenic mechanism. Full article

(This article belongs to the Special Issue Helicobacter pylori Infection–Inducement of Gastroenteric Diseases)

21 pages, 2366 KiB

Open AccessEditor’s ChoiceArticle

First Detection of Microcystin-LR in the Amazon River at the Drinking Water Treatment Plant of the Municipality of Macapá, Brazil

by Elane D.C. Oliveira, Raquel Castelo-Branco, Luis Silva, Natalina Silva, Joana Azevedo, Vitor Vasconcelos, Silvia Faustino and Alan Cunha

Toxins 2019, 11(11), 669; https://doi.org/10.3390/toxins11110669 - 15 Nov 2019

Cited by 25 | Viewed by 4910

Abstract

Human poisoning by microcystin has been recorded in many countries, including Brazil, where fatal cases have already occurred. The Amazon River is the main source of drinking water in municipalities such as Macapá, where there is no monitoring of cyanobacteria and cyanotoxins. This [...] Read more.

Human poisoning by microcystin has been recorded in many countries, including Brazil, where fatal cases have already occurred. The Amazon River is the main source of drinking water in municipalities such as Macapá, where there is no monitoring of cyanobacteria and cyanotoxins. This study investigated the presence of cyanobacteria and cyanotoxins in samples from a drinking water treatment plant (DWTP) that catches water from the Amazon River. The toxin analyses employed ELISA, LC/MS, and molecular screening for genes involved in the production of cyanotoxins. The sampling was carried out monthly from April 2015 to April 2016 at the intake (raw water) and exit (treated water) of the DWTP. This study reports the first detection of microcystin-LR (MC-LR) in the Amazon River, the world’s largest river, and in its treated water destined for drinking water purposes in Macapá, Brazil. The cyanobacterial density and MC-LR concentration were both low during the year. However, Limnothrix planctonica showed a density peak (± 900 cells mL⁻¹) in the quarter of June–August 2015, when MC-LR was registered (2.1 µg L⁻¹). Statistical analyses indicate that L. planctonica may produce the microcystin. Full article

(This article belongs to the Special Issue Freshwater Cyanobacterial Toxins: Developments in Monitoring, Identification, Impacts and Factors Influencing Production)

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14 pages, 6678 KiB

Open AccessEditor’s ChoiceArticle

Deoxynivalenol Induces Intestinal Damage and Inflammatory Response through the Nuclear Factor-κB Signaling Pathway in Piglets

by Xi-Chun Wang, Ya-Fei Zhang, Li Cao, Lei Zhu, Ying-Ying Huang, Xiao-Fang Chen, Xiao-Yan Chu, Dian-Feng Zhu, Sajid Ur Rahman, Shi-Bin Feng, Yu Li and Jin-Jie Wu

Toxins 2019, 11(11), 663; https://doi.org/10.3390/toxins11110663 - 14 Nov 2019

Cited by 36 | Viewed by 3765

Abstract

Deoxynivalenol (DON) is highly toxic to animals and humans, but pigs are most sensitive to it. The porcine mucosal injury related mechanism of DON is not yet fully clarified. Here, we investigated DON-induced injury in the intestinal tissues of piglet. Thirty weanling piglets [...] Read more.

Deoxynivalenol (DON) is highly toxic to animals and humans, but pigs are most sensitive to it. The porcine mucosal injury related mechanism of DON is not yet fully clarified. Here, we investigated DON-induced injury in the intestinal tissues of piglet. Thirty weanling piglets [(Duroc × Landrace) × Yorkshire] were randomly divided into three groups according to single factor experimental design (10 piglets each group). Piglets were fed a basal diet in the control group, while low and high dose groups were fed a DON diet (1300 and 2200 μg/kg, respectively) for 60 days. Scanning electron microscopy results indicated that the ultrastructure of intestinal epithelial cells in the DON-treated group was damaged. The distribution and optical density (OD) values of zonula occludens 1 (ZO-1) protein in the intestinal tissues of DON-treated groups were decreased. At higher DON dosage, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α mRNA levels were elevated in the intestinal tissues. The mRNA and protein levels of NF-κB p65, IκB-α, IKKα/β, iNOS, and COX-2 in the small intestinal mucosa were abnormally altered with an increase in DON concentration. These results indicate that DON can persuade intestinal damage and inflammatory responses in piglets via the nuclear factor-κB signaling pathway. Full article

(This article belongs to the Section Mycotoxins)

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22 pages, 1707 KiB

Open AccessEditor’s ChoiceReview

Fusarium-Produced Mycotoxins in Plant-Pathogen Interactions

by Lakshmipriya Perincherry, Justyna Lalak-Kańczugowska and Łukasz Stępień

Toxins 2019, 11(11), 664; https://doi.org/10.3390/toxins11110664 - 14 Nov 2019

Cited by 192 | Viewed by 14684

Abstract

Pathogens belonging to the Fusarium genus are causal agents of the most significant crop diseases worldwide. Virtually all Fusarium species synthesize toxic secondary metabolites, known as mycotoxins; however, the roles of mycotoxins are not yet fully understood. To understand how a fungal partner [...] Read more.

Pathogens belonging to the Fusarium genus are causal agents of the most significant crop diseases worldwide. Virtually all Fusarium species synthesize toxic secondary metabolites, known as mycotoxins; however, the roles of mycotoxins are not yet fully understood. To understand how a fungal partner alters its lifestyle to assimilate with the plant host remains a challenge. The review presented the mechanisms of mycotoxin biosynthesis in the Fusarium genus under various environmental conditions, such as pH, temperature, moisture content, and nitrogen source. It also concentrated on plant metabolic pathways and cytogenetic changes that are influenced as a consequence of mycotoxin confrontations. Moreover, we looked through special secondary metabolite production and mycotoxins specific for some significant fungal pathogens-plant host models. Plant strategies of avoiding the Fusarium mycotoxins were also discussed. Finally, we outlined the studies on the potential of plant secondary metabolites in defense reaction to Fusarium infection. Full article

(This article belongs to the Special Issue Mycotoxigenic Fungi and Their Interactions with Plants)

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22 pages, 2439 KiB

Open AccessEditor’s ChoiceReview

The Diversity of Venom: The Importance of Behavior and Venom System Morphology in Understanding Its Ecology and Evolution

by Vanessa Schendel, Lachlan D. Rash, Ronald A. Jenner and Eivind A. B. Undheim

Toxins 2019, 11(11), 666; https://doi.org/10.3390/toxins11110666 - 14 Nov 2019

Cited by 169 | Viewed by 22801

Abstract

Venoms are one of the most convergent of animal traits known, and encompass a much greater taxonomic and functional diversity than is commonly appreciated. This knowledge gap limits the potential of venom as a model trait in evolutionary biology. Here, we summarize the [...] Read more.

Venoms are one of the most convergent of animal traits known, and encompass a much greater taxonomic and functional diversity than is commonly appreciated. This knowledge gap limits the potential of venom as a model trait in evolutionary biology. Here, we summarize the taxonomic and functional diversity of animal venoms and relate this to what is known about venom system morphology, venom modulation, and venom pharmacology, with the aim of drawing attention to the importance of these largely neglected aspects of venom research. We find that animals have evolved venoms at least 101 independent times and that venoms play at least 11 distinct ecological roles in addition to predation, defense, and feeding. Comparisons of different venom systems suggest that morphology strongly influences how venoms achieve these functions, and hence is an important consideration for understanding the molecular evolution of venoms and their toxins. Our findings also highlight the need for more holistic studies of venom systems and the toxins they contain. Greater knowledge of behavior, morphology, and ecologically relevant toxin pharmacology will improve our understanding of the evolution of venoms and their toxins, and likely facilitate exploration of their potential as sources of molecular tools and therapeutic and agrochemical lead compounds. Full article

(This article belongs to the Special Issue Evolutionary Ecology of Venom)

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34 pages, 1686 KiB

Open AccessEditor’s ChoiceReview

Hemolysis Derived Products Toxicity and Endothelium: Model of the Second Hit

by Marie Frimat, Idris Boudhabhay and Lubka T. Roumenina

Toxins 2019, 11(11), 660; https://doi.org/10.3390/toxins11110660 - 13 Nov 2019

Cited by 61 | Viewed by 12920

Abstract

Vascular diseases are multifactorial, often requiring multiple challenges, or ‘hits’, for their initiation. Intra-vascular hemolysis illustrates well the multiple-hit theory where a first event lyses red blood cells, releasing hemolysis-derived products, in particular cell-free heme which is highly toxic for the endothelium. Physiologically, [...] Read more.

Vascular diseases are multifactorial, often requiring multiple challenges, or ‘hits’, for their initiation. Intra-vascular hemolysis illustrates well the multiple-hit theory where a first event lyses red blood cells, releasing hemolysis-derived products, in particular cell-free heme which is highly toxic for the endothelium. Physiologically, hemolysis derived-products are rapidly neutralized by numerous defense systems, including haptoglobin and hemopexin which scavenge hemoglobin and heme, respectively. Likewise, cellular defense mechanisms are involved, including heme-oxygenase 1 upregulation which metabolizes heme. However, in cases of intra-vascular hemolysis, those systems are overwhelmed. Heme exerts toxic effects by acting as a damage-associated molecular pattern and promoting, together with hemoglobin, nitric oxide scavenging and ROS production. In addition, it activates the complement and the coagulation systems. Together, these processes lead to endothelial cell injury which triggers pro-thrombotic and pro-inflammatory phenotypes. Moreover, among endothelial cells, glomerular ones display a particular susceptibility explained by a weaker capacity to counteract hemolysis injury. In this review, we illustrate the ‘multiple-hit’ theory through the example of intra-vascular hemolysis, with a particular focus on cell-free heme, and we advance hypotheses explaining the glomerular susceptibility observed in hemolytic diseases. Finally, we describe therapeutic options for reducing endothelial injury in hemolytic diseases. Full article

(This article belongs to the Special Issue The Endothelial Effects of Uremic Toxins)

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13 pages, 2004 KiB

Open AccessEditor’s ChoiceReview

Structure–Function Relationships of the Repeat Domains of RTX Toxins

by Ulrich Baumann

Toxins 2019, 11(11), 657; https://doi.org/10.3390/toxins11110657 - 12 Nov 2019

Cited by 18 | Viewed by 5017

Abstract

RTX proteins are a large family of polypeptides of mainly Gram-negative origin that are secreted into the extracellular medium by a type I secretion system featuring a non-cleavable C-terminal secretion signal, which is preceded by a variable number of nine-residue tandem repeats. The [...] Read more.

RTX proteins are a large family of polypeptides of mainly Gram-negative origin that are secreted into the extracellular medium by a type I secretion system featuring a non-cleavable C-terminal secretion signal, which is preceded by a variable number of nine-residue tandem repeats. The three-dimensional structure forms a parallel β-roll, where β-strands of two parallel sheets are connected by calcium-binding linkers in such a way that a right-handed spiral is built. The Ca²⁺ ions are an integral part of the structure, which cannot form without them. The structural determinants of this unique architecture will be reviewed with its conservations and variations together with the implication for secretion and folding of these proteins. The general purpose of the RTX domains appears to act as an internal chaperone that keeps the polypeptide unfolded in the calcium-deprived cytosol and triggers folding in the calcium-rich extracellular medium. A rather recent addition to the structural biology of the RTX toxin is a variant occurring in a large RTX adhesin, where this non-canonical β-roll binds to ice and diatoms. Full article

(This article belongs to the Special Issue RTX Toxins)

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18 pages, 998 KiB

Open AccessEditor’s ChoiceArticle

Multiple Mycotoxins Determination in Food by LC-MS/MS: An International Collaborative Study

by Thomas Bessaire, Claudia Mujahid, Pascal Mottier and Aurélien Desmarchelier

Toxins 2019, 11(11), 658; https://doi.org/10.3390/toxins11110658 - 12 Nov 2019

Cited by 55 | Viewed by 8368

Abstract

An intercollaborative study was organized to evaluate the performance characteristics of a liquid chromatography tandem mass spectrometry procedure for the simultaneous determination of 12 mycotoxins in food, which were ochratoxin A, aflatoxins B1, B2, G1, G2, and M1, deoxynivalenol, zearalenone, fumonisins B1 and [...] Read more.

An intercollaborative study was organized to evaluate the performance characteristics of a liquid chromatography tandem mass spectrometry procedure for the simultaneous determination of 12 mycotoxins in food, which were ochratoxin A, aflatoxins B1, B2, G1, G2, and M1, deoxynivalenol, zearalenone, fumonisins B1 and B2, and T-2 and HT-2 toxins. The method combined the simplicity of the QuEChERS (Quick, Easy, Cheap, Efficient, Rugged and Safe) approach with the efficiency of immunoaffinity column cleanup (the step used to enhance sensitivity and sample cleanup for some matrices only). Twenty-three entities were enrolled and were European reference laboratories for mycotoxin analysis, U.S. and European service laboratories, and Nestlé laboratories. Each participant analyzed 28 incurred and/or spiked blind samples composed of spices, nuts, milk powder, dried fruits, cereals, and baby food using the protocol given. Method performances were assessed according to ISO 5725-2. Relative standard deviations of repeatability and reproducibility and trueness values for each of the 115 mycotoxin/sample combinations ranged from 5% to 23%, 7% to 26%, and 85% to 129%, respectively, in line with requirements defined in EC 401/2006. The overall set of data gathered demonstrated that the method offered a unique platform to ensure compliance with EC 1881/2006 and EC 165/2013 regulations setting maximum limits for mycotoxins in food samples, even at low regulated levels for foods intended for infants and young children. The method was applicable regardless of the food, the regulated mycotoxin, and the concentration level, and thus is an excellent candidate for future standardization. Full article

(This article belongs to the Special Issue Application of LC-MS/MS in the Mycotoxins Studies)

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14 pages, 1456 KiB

Open AccessEditor’s ChoiceArticle

Comparative In Vitro Assessment of a Range of Commercial Feed Additives with Multiple Mycotoxin Binding Claims

by Oluwatobi Kolawole, Julie Meneely, Brett Greer, Olivier Chevallier, David S. Jones, Lisa Connolly and Christopher Elliott

Toxins 2019, 11(11), 659; https://doi.org/10.3390/toxins11110659 - 12 Nov 2019

Cited by 46 | Viewed by 7968

Abstract

Contamination of animal feed with multiple mycotoxins is an ongoing and growing issue, as over 60% of cereal crops worldwide have been shown to be contaminated with mycotoxins. The present study was carried out to assess the efficacy of commercial feed additives sold [...] Read more.

Contamination of animal feed with multiple mycotoxins is an ongoing and growing issue, as over 60% of cereal crops worldwide have been shown to be contaminated with mycotoxins. The present study was carried out to assess the efficacy of commercial feed additives sold with multi-mycotoxin binding claims. Ten feed additives were obtained and categorised into three groups based on their main composition. Their capacity to simultaneously adsorb deoxynivalenol (DON), zearalenone (ZEN), fumonisin B1 (FB1), ochratoxin A (OTA), aflatoxin B1 (AFB1) and T-2 toxin was assessed and compared using an in vitro model designed to simulate the gastrointestinal tract of a monogastric animal. Results showed that only one product (a modified yeast cell wall) effectively adsorbed more than 50% of DON, ZEN, FB1, OTA, T-2 and AFB1, in the following order: AFB1 > ZEN > T-2 > DON > OTA > FB1. The remaining products were able to moderately bind AFB1 (44–58%) but had less, or in some cases, no effect on ZEN, FB1, OTA and T-2 binding (<35%). It is important for companies producing mycotoxin binders that their products undergo rigorous trials under the conditions which best mimic the environment that they must be active in. Claims on the binding efficiency should only be made when such data has been generated. Full article

(This article belongs to the Special Issue Mycotoxin Contamination Management Tools and Efficient Strategies in Feed Industry)

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28 pages, 4225 KiB

Open AccessEditor’s ChoiceReview

The Biological Activity of Natural Alkaloids against Herbivores, Cancerous Cells and Pathogens

by Amin Thawabteh, Salma Juma, Mariam Bader, Donia Karaman, Laura Scrano, Sabino A. Bufo and Rafik Karaman

Toxins 2019, 11(11), 656; https://doi.org/10.3390/toxins11110656 - 11 Nov 2019

Cited by 227 | Viewed by 13952

Abstract

The growing incidence of microorganisms that resist antimicrobials is a constant concern for the scientific community, while the development of new antimicrobials from new chemical entities has become more and more expensive, time-consuming, and exacerbated by emerging drug-resistant strains. In this regard, many [...] Read more.

The growing incidence of microorganisms that resist antimicrobials is a constant concern for the scientific community, while the development of new antimicrobials from new chemical entities has become more and more expensive, time-consuming, and exacerbated by emerging drug-resistant strains. In this regard, many scientists are conducting research on plants aiming to discover possible antimicrobial compounds. The secondary metabolites contained in plants are a source of chemical entities having pharmacological activities and intended to be used for the treatment of different diseases. These chemical entities have the potential to be used as an effective antioxidant, antimutagenic, anticarcinogenic and antimicrobial agents. Among these pharmacologically active entities are the alkaloids which are classified into a number of classes, including pyrrolizidines, pyrrolidines, quinolizidines, indoles, tropanes, piperidines, purines, imidazoles, and isoquinolines. Alkaloids that have antioxidant properties are capable of preventing a variety of degenerative diseases through capturing free radicals, or through binding to catalysts involved indifferent oxidation processes occurring within the human body. Furthermore, these entities are capable of inhibiting the activity of bacteria, fungi, protozoan and etc. The unique properties of these secondary metabolites are the main reason for their utilization by the pharmaceutical companies for the treatment of different diseases. Generally, these alkaloids are extracted from plants, animals and fungi. Penicillin is the most famous natural drug discovery deriving from fungus. Similarly, marines have been used as a source for thousands of bioactive marine natural products. In this review, we cover the medical use of natural alkaloids isolated from a variety of plants and utilized by humans as antibacterial, antiviral, antifungal and anticancer agents. An example for such alkaloids is berberine, an isoquinoline alkaloid, found in roots and stem-bark of Berberis asculin P. Renault plant and used to kill a variety of microorganisms. Full article

(This article belongs to the Special Issue Biological Activities of Alkaloids: From Toxicology to Pharmacology)

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13 pages, 596 KiB

Open AccessEditor’s ChoiceArticle

Toxin Production in Soybean (Glycine max L.) Plants with Charcoal Rot Disease and by Macrophomina phaseolina, the Fungus that Causes the Disease

by Hamed K. Abbas, Nacer Bellaloui, Cesare Accinelli, James R. Smith and W. Thomas Shier

Toxins 2019, 11(11), 645; https://doi.org/10.3390/toxins11110645 - 6 Nov 2019

Cited by 35 | Viewed by 5230

Abstract

Charcoal rot disease, caused by the fungus Macrophomina phaseolina, results in major economic losses in soybean production in southern USA. M. phaseolina has been proposed to use the toxin (-)-botryodiplodin in its root infection mechanism to create a necrotic zone in root [...] Read more.

Charcoal rot disease, caused by the fungus Macrophomina phaseolina, results in major economic losses in soybean production in southern USA. M. phaseolina has been proposed to use the toxin (-)-botryodiplodin in its root infection mechanism to create a necrotic zone in root tissue through which fungal hyphae can readily enter the plant. The majority (51.4%) of M. phaseolina isolates from plants with charcoal rot disease produced a wide range of (-)-botryodiplodin concentrations in a culture medium (0.14–6.11 µg/mL), 37.8% produced traces below the limit of quantification (0.01 µg/mL), and 10.8% produced no detectable (-)-botryodiplodin. Some culture media with traces or no (-)-botryodiplodin were nevertheless strongly phytotoxic in soybean leaf disc cultures, consistent with the production of another unidentified toxin(s). Widely ranging (-)-botryodiplodin levels (traces to 3.14 µg/g) were also observed in the roots, but not in the aerial parts, of soybean plants naturally infected with charcoal rot disease. This is the first report of (-)-botryodiplodin in plant tissues naturally infected with charcoal rot disease. No phaseolinone was detected in M. phaseolina culture media or naturally infected soybean tissues. These results are consistent with (-)-botryodiplodin playing a role in the pathology of some, but not all, M. phaseolina isolates from soybeans with charcoal rot disease in southern USA. Full article

(This article belongs to the Special Issue Mycotoxins in Feed and Food Chain: Present Status and Future Concerns)

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13 pages, 1294 KiB

Open AccessEditor’s ChoiceArticle

A Novel Niosome-Encapsulated Essential Oil Formulation to Prevent Aspergillus flavus Growth and Aflatoxin Contamination of Maize Grains During Storage

by Marta García-Díaz, Belén Patiño, Covadonga Vázquez and Jessica Gil-Serna

Toxins 2019, 11(11), 646; https://doi.org/10.3390/toxins11110646 - 6 Nov 2019

Cited by 51 | Viewed by 5629

Abstract

Aflatoxin (AF) contamination of maize is a major concern for food safety. The use of chemical fungicides is controversial, and it is necessary to develop new effective methods to control Aspergillus flavus growth and, therefore, to avoid the presence of AFs in grains. [...] Read more.

Aflatoxin (AF) contamination of maize is a major concern for food safety. The use of chemical fungicides is controversial, and it is necessary to develop new effective methods to control Aspergillus flavus growth and, therefore, to avoid the presence of AFs in grains. In this work, we tested in vitro the effect of six essential oils (EOs) extracted from aromatic plants. We selected those from Satureja montana and Origanum virens because they show high levels of antifungal and antitoxigenic activity at low concentrations against A. flavus. EOs are highly volatile compounds and we have developed a new niosome-based encapsulation method to extend their shelf life and activity. These new formulations have been successfully applied to reduce fungal growth and AF accumulation in maize grains in a small-scale test, as well as placing the maize into polypropylene woven bags to simulate common storage conditions. In this latter case, the antifungal properties lasted up to 75 days after the first application. Full article

(This article belongs to the Special Issue Novel Approaches to Minimising Mycotoxin Contamination)

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23 pages, 1431 KiB

Open AccessEditor’s ChoiceReview

FGF23 and Phosphate–Cardiovascular Toxins in CKD

by Isabel Vogt, Dieter Haffner and Maren Leifheit-Nestler

Toxins 2019, 11(11), 647; https://doi.org/10.3390/toxins11110647 - 6 Nov 2019

Cited by 68 | Viewed by 15520

Abstract

Elevated levels of fibroblast growth factor 23 (FGF23) and phosphate are highly associated with increased cardiovascular disease and mortality in patients suffering from chronic kidney disease (CKD). As the kidney function declines, serum phosphate levels rise and subsequently induce the secretion of the [...] Read more.

Elevated levels of fibroblast growth factor 23 (FGF23) and phosphate are highly associated with increased cardiovascular disease and mortality in patients suffering from chronic kidney disease (CKD). As the kidney function declines, serum phosphate levels rise and subsequently induce the secretion of the phosphaturic hormone FGF23. In early stages of CKD, FGF23 prevents the increase of serum phosphate levels and thereby attenuates phosphate-induced vascular calcification, whereas in end-stage kidney disease, FGF23 fails to maintain phosphate homeostasis. Both hyperphosphatemia and elevated FGF23 levels promote the development of hypertension, vascular calcification, and left ventricular hypertrophy by distinct mechanisms. Therefore, FGF23 and phosphate are considered promising therapeutic targets to improve the cardiovascular outcome in CKD patients. Previous therapeutic strategies are based on dietary and pharmacological reduction of serum phosphate, and consequently FGF23 levels. However, clinical trials proving the effects on the cardiovascular outcome are lacking. Recent publications provide evidence for new promising therapeutic interventions, such as magnesium supplementation and direct targeting of phosphate and FGF receptors to prevent toxicity of FGF23 and hyperphosphatemia in CKD patients. Full article

(This article belongs to the Special Issue Uremia and Metabolic Complications of Chronic Kidney Disease )

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18 pages, 593 KiB

Open AccessEditor’s ChoiceReview

A Review of the Effect of Trace Metals on Freshwater Cyanobacterial Growth and Toxin Production

by Jordan A. Facey, Simon C. Apte and Simon M. Mitrovic

Toxins 2019, 11(11), 643; https://doi.org/10.3390/toxins11110643 - 5 Nov 2019

Cited by 77 | Viewed by 6641

Abstract

Cyanobacterial blooms are becoming more common in freshwater systems, causing ecological degradation and human health risks through exposure to cyanotoxins. The role of phosphorus and nitrogen in cyanobacterial bloom formation is well documented and these are regularly the focus of management plans. There [...] Read more.

Cyanobacterial blooms are becoming more common in freshwater systems, causing ecological degradation and human health risks through exposure to cyanotoxins. The role of phosphorus and nitrogen in cyanobacterial bloom formation is well documented and these are regularly the focus of management plans. There is also strong evidence that trace metals are required for a wide range of cellular processes, however their importance as a limiting factor of cyanobacterial growth in ecological systems is unclear. Furthermore, some studies have suggested a direct link between cyanotoxin production and some trace metals. This review synthesises current knowledge on the following: (1) the biochemical role of trace metals (particularly iron, cobalt, copper, manganese, molybdenum and zinc), (2) the growth limitation of cyanobacteria by trace metals, (3) the trace metal regulation of the phytoplankton community structure and (4) the role of trace metals in cyanotoxin production. Iron dominated the literature and regularly influenced bloom formation, with 15 of 18 studies indicating limitation or colimitation of cyanobacterial growth. A range of other trace metals were found to have a demonstrated capacity to limit cyanobacterial growth, and these metals require further study. The effect of trace metals on cyanotoxin production is equivocal and highly variable. Better understanding the role of trace metals in cyanobacterial growth and bloom formation is an essential component of freshwater management and a direction for future research. Full article

(This article belongs to the Special Issue Freshwater Cyanobacterial Toxins: Developments in Monitoring, Identification, Impacts and Factors Influencing Production)

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29 pages, 727 KiB

Open AccessEditor’s ChoiceReview

Co-Occurrence and Combinatory Effects of Alternaria Mycotoxins and Other Xenobiotics of Food Origin: Current Scenario and Future Perspectives

by Francesco Crudo, Elisabeth Varga, Georg Aichinger, Gianni Galaverna, Doris Marko, Chiara Dall’Asta and Luca Dellafiora

Toxins 2019, 11(11), 640; https://doi.org/10.3390/toxins11110640 - 3 Nov 2019

Cited by 70 | Viewed by 6666

Abstract

Mycotoxins are low-molecular weight compounds produced by diverse genera of molds that may contaminate food and feed threatening the health of humans and animals. Recent findings underline the importance of studying the combined occurrence of multiple mycotoxins and the relevance of assessing the [...] Read more.

Mycotoxins are low-molecular weight compounds produced by diverse genera of molds that may contaminate food and feed threatening the health of humans and animals. Recent findings underline the importance of studying the combined occurrence of multiple mycotoxins and the relevance of assessing the toxicity their simultaneous exposure may cause in living organisms. In this context, for the first time, this work has critically reviewed the most relevant data concerning the occurrence and toxicity of mycotoxins produced by Alternaria spp., which are among the most important emerging risks to be assessed in food safety, alone or in combination with other mycotoxins and bioactive food constituents. According to the literature covered, multiple Alternaria mycotoxins may often occur simultaneously in contaminated food, along with several other mycotoxins and food bioactives inherently present in the studied matrices. Although the toxicity of combinations naturally found in food has been rarely assessed experimentally, the data collected so far, clearly point out that chemical mixtures may differ in their toxicity compared to the effect of toxins tested individually. The data presented here may provide a solid foothold to better support the risk assessment of Alternaria mycotoxins highlighting the actual role of chemical mixtures on influencing their toxicity. Full article

(This article belongs to the Special Issue Mycotoxins in Feed and Food Chain: Present Status and Future Concerns)

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