Toxins

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18 pages, 2372 KiB

Open AccessEditor’s ChoiceArticle

Venomics of Trimeresurus (Popeia) nebularis, the Cameron Highlands Pit Viper from Malaysia: Insights into Venom Proteome, Toxicity and Neutralization of Antivenom

by Choo Hock Tan, Kae Yi Tan, Tzu Shan Ng, Evan S.H. Quah, Ahmad Khaldun Ismail, Sumana Khomvilai, Visith Sitprija and Nget Hong Tan

Toxins 2019, 11(2), 95; https://doi.org/10.3390/toxins11020095 - 6 Feb 2019

Cited by 42 | Viewed by 7189

Abstract

Trimeresurus nebularis is a montane pit viper that causes bites and envenomation to various communities in the central highland region of Malaysia, in particular Cameron’s Highlands. To unravel the venom composition of this species, the venom proteins were digested by trypsin and subjected [...] Read more.

Trimeresurus nebularis is a montane pit viper that causes bites and envenomation to various communities in the central highland region of Malaysia, in particular Cameron’s Highlands. To unravel the venom composition of this species, the venom proteins were digested by trypsin and subjected to nano-liquid chromatography-tandem mass spectrometry (LC-MS/MS) for proteomic profiling. Snake venom metalloproteinases (SVMP) dominated the venom proteome by 48.42% of total venom proteins, with a characteristic distribution of P-III: P-II classes in a ratio of 2:1, while P-I class was undetected. Snaclecs constituted the second most venomous protein family (19.43%), followed by snake venom serine proteases (SVSP, 14.27%), phospholipases A₂ (5.40%), disintegrins (5.26%) and minor proteins including cysteine-rich secretory proteins, L-amino acid oxidases, phosphodiesterases, 5′-nucleotidases. The venomic profile correlates with local (painful progressive edema) and systemic (hemorrhage, coagulopathy, thrombocytopenia) manifestation of T. nebularis envenoming. As specific antivenom is unavailable for T. nebularis, the hetero-specific Thai Green Pit viper Monovalent Antivenom (GPVAV) was examined for immunological cross-reactivity. GPVAV exhibited good immunoreactivity to T. nebularis venom and the antivenom effectively cross-neutralized the hemotoxic and lethal effects of T. nebularis (lethality neutralizing potency = 1.6 mg venom per mL antivenom). The findings supported GPVAV use in treating T. nebularis envenoming. Full article

(This article belongs to the Section Animal Venoms)

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21 pages, 5071 KiB

Open AccessEditor’s ChoiceArticle

Chronic In Vivo Effects of Repeated Exposure to Low Oral Doses of Tetrodotoxin: Preliminary Evidence of Nephrotoxicity and Cardiotoxicity

by Andrea Boente-Juncal, Carmen Vale, Manuel Cifuentes, Paz Otero, Mercedes Camiña, Mercedes Rodriguez-Vieytes and Luis Miguel Botana

Toxins 2019, 11(2), 96; https://doi.org/10.3390/toxins11020096 - 6 Feb 2019

Cited by 19 | Viewed by 4460

Abstract

Tetrodotoxin (TTX) is one of the most potent naturally occurring neurotoxins. Initially TTX was associated with human food intoxications in Japan, but nowadays, concerns about the human health risks posed by TTX have increased in Europe after the identification of the toxin in [...] Read more.

Tetrodotoxin (TTX) is one of the most potent naturally occurring neurotoxins. Initially TTX was associated with human food intoxications in Japan, but nowadays, concerns about the human health risks posed by TTX have increased in Europe after the identification of the toxin in fish, marine gastropods, and bivalves captured in European waters. Even when TTX monitoring is not currently performed in Europe, an acute oral no observable effect level (NOAEL) of 75 μg/kg has been recently established but, to date, no studies evaluating the chronic oral toxicity of TTX have been released, even when EFSA has highlighted the need for them. Thus, in this work, the chronic effects of low oral TTX doses (below the acute lethal dose 50) were evaluated following internationally adopted guidelines. The results presented here demonstrate that low oral doses of TTX have deleterious effects on renal and cardiac tissues. Moreover, alterations in blood biochemistry parameters, urine production, and urinalysis data were already detected at the oral dose of 75 µg/kg after the 28 days exposure. Thus, the data presented here constitute an initial approach for the chronic evaluation of the in vivo toxicity of tetrodotoxin after its ingestion through contaminated fishery products. Full article

(This article belongs to the Special Issue Marine Toxins Affecting Neuronal Function)

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26 pages, 3562 KiB

Open AccessEditor’s ChoiceArticle

RNA-Seq Transcriptome Profiling of the Queen Scallop (Aequipecten opercularis) Digestive Gland after Exposure to Domoic Acid-Producing Pseudo-nitzschia

by Pablo Ventoso, Antonio J. Pazos, M. Luz Pérez-Parallé, Juan Blanco, Juan C. Triviño and José L. Sánchez

Toxins 2019, 11(2), 97; https://doi.org/10.3390/toxins11020097 - 6 Feb 2019

Cited by 20 | Viewed by 6418

Abstract

Some species of the genus Pseudo-nitzschia produce the toxin domoic acid, which causes amnesic shellfish poisoning (ASP). Given that bivalve mollusks are filter feeders, they can accumulate these toxins in their tissues. To elucidate the transcriptional response of the queen scallop Aequipecten opercularis [...] Read more.

Some species of the genus Pseudo-nitzschia produce the toxin domoic acid, which causes amnesic shellfish poisoning (ASP). Given that bivalve mollusks are filter feeders, they can accumulate these toxins in their tissues. To elucidate the transcriptional response of the queen scallop Aequipecten opercularis after exposure to domoic acid-producing Pseudo-nitzschia, the digestive gland transcriptome was de novo assembled using an Illumina HiSeq 2000 platform. Then, a differential gene expression analysis was performed. After the assembly, 142,137 unigenes were obtained, and a total of 10,144 genes were differentially expressed in the groups exposed to the toxin. Functional enrichment analysis found that 374 Pfam (protein families database) domains were significantly enriched. The C1q domain, the C-type lectin, the major facilitator superfamily, the immunoglobulin domain, and the cytochrome P450 were among the most enriched Pfam domains. Protein network analysis showed a small number of highly connected nodes involved in specific functions: proteasome components, mitochondrial ribosomal proteins, protein translocases of mitochondrial membranes, cytochromes P450, and glutathione S-transferases. The results suggest that exposure to domoic acid-producing organisms causes oxidative stress and mitochondrial dysfunction. The transcriptional response counteracts these effects with the up-regulation of genes coding for some mitochondrial proteins, proteasome components, and antioxidant enzymes (glutathione S-transferases, thioredoxins, glutaredoxins, and copper/zinc superoxide dismutases). Full article

(This article belongs to the Collection Toxicological Challenges of Aquatic Toxins)

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13 pages, 18236 KiB

Open AccessEditor’s ChoiceArticle

Venom in Furs: Facial Masks as Aposematic Signals in a Venomous Mammal

by K. Anne-Isola Nekaris, Ariana Weldon, Muhammad Ali Imron, Keely Q. Maynard, Vincent Nijman, Stephanie A. Poindexter and Thais Queiroz Morcatty

Toxins 2019, 11(2), 93; https://doi.org/10.3390/toxins11020093 - 5 Feb 2019

Cited by 22 | Viewed by 10120

Abstract

The function of colouration in animals includes concealment, communication and signaling, such as the use of aposematism as a warning signal. Aposematism is unusual in mammals, and exceptions help us to understand its ecology and evolution. The Javan slow loris is a highly [...] Read more.

The function of colouration in animals includes concealment, communication and signaling, such as the use of aposematism as a warning signal. Aposematism is unusual in mammals, and exceptions help us to understand its ecology and evolution. The Javan slow loris is a highly territorial venomous mammal that has a distinctive facial mask and monochromatic vision. To help understand if they use aposematism to advertise their venom to conspecifics or predators with different visual systems, we studied a population in Java, Indonesia. Using ImageJ, we selected colours from the facial masks of 58 individuals, converted RBG colours into monochromatic, dichromatic and trichromatic modes, and created a contrast index. During 290 captures, we recorded venom secretion and aggressiveness. Using Non-metric Multidimensional Scaling and generalised additive models for location, scale and shape, we found that young slow lorises differ significantly from adults, being both more contrasting and more aggressive, with aggressive animals showing fewer wounds. We suggest aposematic facial masks serve multiple purposes in slow lorises based on age. Change in colouration through development may play a role in intraspecific competition, and advertise toxicity or aggressiveness to competitors and/or predators in juveniles. Aposematic signals combined with intraspecific competition may provide clues to new venomous taxa among mammals. Full article

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

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24 pages, 1542 KiB

Open AccessEditor’s ChoiceArticle

Subclinical Lipopolysaccharide from Salmonella Enteritidis Induces Dysregulation of Bioactive Substances from Selected Brain Sections and Glands of Neuroendocrine Axes

by Anita Mikołajczyk and Dagmara Złotkowska

Toxins 2019, 11(2), 91; https://doi.org/10.3390/toxins11020091 - 2 Feb 2019

Cited by 12 | Viewed by 3530

Abstract

Bacterial lipopolysaccharide (LPS) can contribute to the pathogenesis and the clinical symptoms of many diseases such as cancer, mental disorders, neurodegenerative as well as metabolic diseases. The asymptomatic carrier state of Salmonella spp. is a very important public health problem. A subclinical single [...] Read more.

Bacterial lipopolysaccharide (LPS) can contribute to the pathogenesis and the clinical symptoms of many diseases such as cancer, mental disorders, neurodegenerative as well as metabolic diseases. The asymptomatic carrier state of Salmonella spp. is a very important public health problem. A subclinical single dose of LPS obtained from S. Enteritidis (5 μg/kg, i.v.) was administered to discern the consequences of changes of various brain peptides such as corticotropin-releasing hormone (CRH), gonadotropin-releasing hormone (GnRH), thyrotropin-releasing hormone (TRH), galanin (GAL), neuropeptide Y (NPY), somatostatin (SOM), substance P (SP), and vasoactive intestinal polypeptide (VIP) in selected clinically important brain sections and endocrine glands of the hypothalamic-pituitary-adrenal (HPA), -thyroid (HPT), -ovarian (HPO) axes. The study was conducted on ten immature crossbred female pigs. The brain peptides were extracted from the hypothalamus (medial basal hypothalamus, preoptic area, lateral hypothalamic area, mammillary bodies, and the stalk median eminence), and pituitary gland (adenohypophysis and neurohypophysis) sections and from the ovaries and adrenal and thyroid glands. There was no difference in health status between LPS and the control groups during the period of the experiment. Nevertheless, even a low single dose of LPS from S. Enteritidis that did not result in any clinical symptoms of disease induced dysregulation of various brain peptides, such as CRH, GnRH, TRH, GAL, NPY, SOM, SP, and VIP in selected brain sections of hypothalamus, pituitary gland and in the endocrine glands of the HPA, HPO, and HPT axes. In conclusion, the obtained results clearly show that subclinical LPS from S. Enteritidis can affect the brain chemistry structure and dysregulate bioactive substance from selected brain sections and glands of the neuroendocrine axes. The exact mechanisms by which LPS can influence major neuroendocrine axes are not fully understood and require further studies. Full article

(This article belongs to the Section Bacterial Toxins)

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14 pages, 1281 KiB

Open AccessEditor’s ChoiceArticle

Comparative Proteomics of Peritrophic Matrix Provides an Insight into its Role in Cry1Ac Resistance of Cotton Bollworm Helicoverpa armigera

by Minghui Jin, Chongyu Liao, Swapan Chakrabarty, Kongming Wu and Yutao Xiao

Toxins 2019, 11(2), 92; https://doi.org/10.3390/toxins11020092 - 2 Feb 2019

Cited by 15 | Viewed by 4484

Abstract

Crystalline (Cry) proteins from Bacillus thuringiensis (Bt) are widely used in sprays and transgenic crops to control insect pests, but the evolution of insect resistance threatens their long-term use. Different resistance mechanisms have been identified, but some have not been completely elucidated. Here, [...] Read more.

Crystalline (Cry) proteins from Bacillus thuringiensis (Bt) are widely used in sprays and transgenic crops to control insect pests, but the evolution of insect resistance threatens their long-term use. Different resistance mechanisms have been identified, but some have not been completely elucidated. Here, the transcriptome of the midgut and proteome of the peritrophic matrix (PM) were comparatively analyzed to identify potential mechanism of resistance to Cry1Ac in laboratory-selected strain XJ10 of Helicoverpa armigera. This strain had a 146-fold resistance to Cry1Ac protoxin and 45-fold resistance to Cry1Ac activated toxin compared with XJ strain. The mRNA and protein levels for several trypsin genes were downregulated in XJ10 compared to the susceptible strain XJ. Furthermore, 215 proteins of the PM were identified, and nearly all had corresponding mRNAs in the midgut. These results provide new insights that the PM may participate in Bt resistance. Full article

(This article belongs to the Special Issue Insecticidal Toxins from Bacillus thuringiensis)

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22 pages, 2880 KiB

Open AccessEditor’s ChoiceArticle

Biological System Responses of Dairy Cows to Aflatoxin B1 Exposure Revealed with Metabolomic Changes in Multiple Biofluids

by Qian Wang, Yangdong Zhang, Nan Zheng, Liya Guo, Xiaoming Song, Shengguo Zhao and Jiaqi Wang

Toxins 2019, 11(2), 77; https://doi.org/10.3390/toxins11020077 - 1 Feb 2019

Cited by 52 | Viewed by 5176

Abstract

Research on mycotoxins now requires a systematic study of post-exposure organisms. In this study, the effects of aflatoxin B1 (AFB1) on biofluids biomarkers were examined with metabolomics and biochemical tests. The results showed that milk concentration of aflatoxin M1 changed with the addition [...] Read more.

Research on mycotoxins now requires a systematic study of post-exposure organisms. In this study, the effects of aflatoxin B1 (AFB1) on biofluids biomarkers were examined with metabolomics and biochemical tests. The results showed that milk concentration of aflatoxin M1 changed with the addition or removal of AFB1. AFB1 significantly affected serum concentrations of superoxide dismutase (SOD) and malon dialdehyde (MDA), SOD/MDA, and the total antioxidant capacity. Significant differences of volatile fatty acids and NH₃-N were detected in the rumen fluid. Eighteen rumen fluid metabolites, 11 plasma metabolites, and 9 milk metabolites were significantly affected by the AFB1. These metabolites are mainly involved in the pathway of amino acids metabolism. Our results suggest that not only is the study of macro-indicators (milk composition and production) important, but that more attention should be paid to micro-indicators (biomarkers) when assessing the risks posed by mycotoxins to dairy cows. Full article

(This article belongs to the Collection Aflatoxins)

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15 pages, 320 KiB

Open AccessEditor’s ChoiceArticle

Occupational Exposure to Mycotoxins in Swine Production: Environmental and Biological Monitoring Approaches

by Susana Viegas, Ricardo Assunção, Carla Martins, Carla Nunes, Bernd Osteresch, Magdalena Twarużek, Robert Kosicki, Jan Grajewski, Edna Ribeiro and Carla Viegas

Toxins 2019, 11(2), 78; https://doi.org/10.3390/toxins11020078 - 1 Feb 2019

Cited by 55 | Viewed by 5892

Abstract

Swine production workers are exposed simultaneously to multiple contaminants. Occupational exposure to aflatoxin B₁ (AFB₁) in Portuguese swine production farms has already been reported. However, besides AFB₁, data regarding fungal contamination showed that exposure to other mycotoxins could [...] Read more.

Swine production workers are exposed simultaneously to multiple contaminants. Occupational exposure to aflatoxin B₁ (AFB₁) in Portuguese swine production farms has already been reported. However, besides AFB₁, data regarding fungal contamination showed that exposure to other mycotoxins could be expected in this setting. The present study aimed to characterize the occupational exposure to multiple mycotoxins of swine production workers. To provide a broad view on the burden of contamination by mycotoxins and the workers’ exposure, biological (urine) samples from workers (n = 25) and 38 environmental samples (air samples, n = 23; litter samples, n = 5; feed samples, n = 10) were collected. The mycotoxins biomarkers detected in the urine samples of the workers group were the deoxynivalenol-glucuronic acid conjugate (60%), aflatoxin M₁ (16%), enniatin B (4%), citrinin (8%), dihydrocitrinone (12%) and ochratoxin A (80%). Results of the control group followed the same pattern, but in general with a lower number of quantifiable results (<LOQ). Besides air samples, all the other environmental samples collected presented high and diverse contamination, and deoxynivalenol (DON), like in the biomonitoring results, was the most prominent mycotoxin. The results demonstrate that the occupational environment is adding and contributing to the workers’ total exposure to mycotoxins, particularly in the case of DON. This was confirmed by the biomonitoring data and the high contamination found in feed and litter samples. Furthermore, he followed multi-biomarker approach allowed to conclude that workers and general population are exposed to several mycotoxins simultaneously. Moreover, occupational exposure is probably described as being intermittent and with very high concentrations for short durations. This should be reflected in the risk assessment process. Full article

(This article belongs to the Special Issue Mycotoxin Exposure and Related Diseases)

19 pages, 1616 KiB

Open AccessEditor’s ChoiceArticle

Structure Elucidation and Biological Evaluation of Maitotoxin-3, a Homologue of Gambierone, from Gambierdiscus belizeanus

by Andrea Boente-Juncal, Mercedes Álvarez, Álvaro Antelo, Inés Rodríguez, Kevin Calabro, Carmen Vale, Olivier P. Thomas and Luis M. Botana

Toxins 2019, 11(2), 79; https://doi.org/10.3390/toxins11020079 - 1 Feb 2019

Cited by 44 | Viewed by 9056

Abstract

Gambierdiscus species are the producers of the marine toxins ciguatoxins and maitotoxins which cause worldwide human intoxications recognized as Ciguatera Fish Poisoning. A deep chemical investigation of a cultured strain of G. belizeanus, collected in the Caribbean Sea, led to the identification [...] Read more.

Gambierdiscus species are the producers of the marine toxins ciguatoxins and maitotoxins which cause worldwide human intoxications recognized as Ciguatera Fish Poisoning. A deep chemical investigation of a cultured strain of G. belizeanus, collected in the Caribbean Sea, led to the identification of a structural homologue of the recently described gambierone isolated from the same strain. The structure was elucidated mainly by comparison of NMR and MS data with those of gambierone and ascertained by 2D NMR data analyses. Gratifyingly, a close inspection of the MS data of the new 44-methylgambierone suggests that this toxin would actually correspond to the structure of maitotoxin-3 (MTX3, m/z 1039.4957 for the protonated adduct) detected in 1994 in a Pacific strain of Gambierdiscus and recently shown in routine monitoring programs. Therefore, this work provides for the first time the chemical identification of the MTX3 molecule by NMR. Furthermore, biological data confirmed the similar activities of both gambierone and 44-methylgambierone. Both gambierone and MTX3 induced a small increase in the cytosolic calcium concentration but only MTX3 caused cell cytotoxicity at micromolar concentrations. Moreover, chronic exposure of human cortical neurons to either gambierone or MTX3 altered the expression of ionotropic glutamate receptors, an effect already described before for the synthetic ciguatoxin CTX3C. However, even when gambierone and MTX3 affected glutamate receptor expression in a similar manner their effect on receptor expression differed from that of CTX3C, since both toxins decreased AMPA receptor levels while increasing N-methyl-d-aspartate (NMDA) receptor protein. Thus, further studies should be pursued to clarify the similarities and differences in the biological activity between the known ciguatoxins and the new identified molecule as well as its contribution to the neurological symptoms of ciguatera. Full article

(This article belongs to the Collection Toxicological Challenges of Aquatic Toxins)

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17 pages, 1036 KiB

Open AccessEditor’s ChoiceArticle

Diverse Components of Resistance to Fusarium verticillioides Infection and Fumonisin Contamination in Four Maize Recombinant Inbred Families

by Laura Morales, Charles T. Zila, Danilo E. Moreta Mejía, Melissa Montoya Arbelaez, Peter J. Balint-Kurti, James B. Holland and Rebecca J. Nelson

Toxins 2019, 11(2), 86; https://doi.org/10.3390/toxins11020086 - 1 Feb 2019

Cited by 19 | Viewed by 5651

Abstract

The fungus Fusarium verticillioides can infect maize ears, causing Fusarium ear rot (FER) and contaminating the grain with fumonisins (FUM), which are harmful to humans and animals. Breeding for resistance to FER and FUM and post-harvest sorting of grain are two strategies for [...] Read more.

The fungus Fusarium verticillioides can infect maize ears, causing Fusarium ear rot (FER) and contaminating the grain with fumonisins (FUM), which are harmful to humans and animals. Breeding for resistance to FER and FUM and post-harvest sorting of grain are two strategies for reducing FUM in the food system. Kernel and cob tissues have been previously associated with differential FER and FUM. Four recombinant inbred line families from the maize nested associated mapping population were grown and inoculated with F. verticillioides across four environments, and we evaluated the kernels for external and internal infection severity as well as FUM contamination. We also employed publicly available phenotypes on innate ear morphology to explore genetic relationships between ear architecture and resistance to FER and FUM. The four families revealed wide variation in external symptomatology at the phenotypic level. Kernel bulk density under inoculation was an accurate indicator of FUM levels. Genotypes with lower kernel density—under both inoculated and uninoculated conditions—and larger cobs were more susceptible to infection and FUM contamination. Quantitative trait locus (QTL) intervals could be classified as putatively resistance-specific and putatively shared for ear and resistance traits. Both types of QTL mapped in this study had substantial overlap with previously reported loci for resistance to FER and FUM. Ear morphology may be a component of resistance to F. verticillioides infection and FUM accumulation. Full article

(This article belongs to the Special Issue Recent Advances in Fusarium Research)

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13 pages, 3633 KiB

Open AccessEditor’s ChoiceArticle

Development of a QuEChERS-Based UHPLC-MS/MS Method for Simultaneous Determination of Six Alternaria Toxins in Grapes

by Wenbo Guo, Kai Fan, Dongxia Nie, Jiajia Meng, Qingwen Huang, Junhua Yang, Yuanyuan Shen, Emmanuel K. Tangni, Zhihui Zhao, Yongjiang Wu and Zheng Han

Toxins 2019, 11(2), 87; https://doi.org/10.3390/toxins11020087 - 1 Feb 2019

Cited by 35 | Viewed by 4376

Abstract

A simple and reliable analytical method for the simultaneous determination of alternariol (AOH), altenuene (ALT), tentoxin (TEN), altenusin (ALS), tenuazonic acid (TeA), and alternariol monomethyl ether (AME) in grapes was developed by ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS). A modified QuEChERS (quick, easy, [...] Read more.

A simple and reliable analytical method for the simultaneous determination of alternariol (AOH), altenuene (ALT), tentoxin (TEN), altenusin (ALS), tenuazonic acid (TeA), and alternariol monomethyl ether (AME) in grapes was developed by ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS). A modified QuEChERS (quick, easy, cheap, effective, rugged, and safe) procedure with the extraction by acetonitrile and purification by sodium chloride (0.5 g) and anhydrous magnesium sulfate (0.5 g) was established to recover the six Alternaria toxins. After validation by determining the linearity (R² > 0.99), recovery (77.8–101.6%), sensitivity (limit of detection in the range of 0.03–0.21 μg kg⁻¹, and limit of quantification in the range of 0.09–0.48 μg kg⁻¹), and precision (relative standard deviation (RSD) ≤ 12.9%), the analytical method was successfully applied to reveal the contamination state of Alternaria toxins in grapes. Among 56 grape samples, 40 (incidence of 71.4%) were contaminated with Alternaria toxins. TEN was the most frequently found mycotoxin (37.5%), with a concentration range of 0.10–1.64 μg kg⁻¹, followed by TeA (28.6%) and AOH (26.8%). ALT (10.7%), AME (3.6%), and ALS (5.4%) were also detected in some samples. To the best of our knowledge, this is the first report about the Alternaria toxins contamination in grapes in China. Full article

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

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16 pages, 1771 KiB

Open AccessEditor’s ChoiceArticle

Contamination of Wheat Cultivated in Various Regions of Poland during 2017 and 2018 Agricultural Seasons with Selected Trichothecenes and Their Modified Forms

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

Toxins 2019, 11(2), 88; https://doi.org/10.3390/toxins11020088 - 1 Feb 2019

Cited by 19 | Viewed by 4156

Abstract

Cross-interaction of antibodies within the immunoaffinity columns used in this study facilitated the simultaneous determination of nivalenol (NIV), deoxynivalenol (DON), their glucoside derivatives (NIV-3G, DON-3G), and 3-acetyl-deoxynivalenol (3-AcDON) in wheat grain harvested in various regions of Poland. In Poland, 2018 was a warm, [...] Read more.

Cross-interaction of antibodies within the immunoaffinity columns used in this study facilitated the simultaneous determination of nivalenol (NIV), deoxynivalenol (DON), their glucoside derivatives (NIV-3G, DON-3G), and 3-acetyl-deoxynivalenol (3-AcDON) in wheat grain harvested in various regions of Poland. In Poland, 2018 was a warm, dry agricultural season, and hence, was relatively less favourable for cereal cultivation than 2017. Data on the natural occurrence of NIV-3G in wheat grain are among the first published in the literature. DON was the most frequently found mycotoxin in the tested samples; the percentage occurrence of DON-positive samples was 92% in 2017 and 61% in 2018. Moreover, DON concentrations were generally higher in 2017 samples (5.2–1670.7 µg/kg) than those in 2018 samples (range 5.0–461.7 µg/kg). A similar pattern was found for DON-3G. However, no statistically significant differences between the samples from the two agricultural seasons were observed for the other three mycotoxins that were analysed, and their concentrations were generally considerably lower. DON was strongly correlated with DON-3G (correlation coefficient r = 0.9558), while NIV was strongly correlated with NIV-3G (r = 0.9442). The percentage occurrence of NIV-3G- and DON-3G-positive samples was 14% in 2017 and 49% in 2018. The NIV-3G/NIV ratio was 5.9–35.7%, while the DON-3G/DON ratio range was 3.2–53.6%. In 2018, wheat samples from Southern Poland exhibited statistically significantly higher levels of DON than those from Northern Poland. The dry and hot summer of 2018 not only reduced wheat yields, but also limited development of Fusarium spp. Therefore, grain harvested that year was generally contaminated with relatively low levels of mycotoxins. Lower levels of DON were also accompanied by lesser amounts of DON-derivatives. Full article

(This article belongs to the Collection Fusarium Toxins – Relevance for Human and Animal Health)

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14 pages, 1233 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Vipera berus berus Venom from Russia: Venomics, Bioactivities and Preclinical Assessment of Microgen Antivenom

by Ruslan I. Al-Shekhadat, Ksenia S. Lopushanskaya, Álvaro Segura, José María Gutiérrez, Juan J. Calvete and Davinia Pla

Toxins 2019, 11(2), 90; https://doi.org/10.3390/toxins11020090 - 1 Feb 2019

Cited by 32 | Viewed by 9067

Abstract

The common European adder, Vipera berus berus, is a medically relevant species, which is widely distributed in Russia and thus, is responsible for most snakebite accidents in Russia. We have investigated the toxic and enzymatic activities and have determined the proteomic composition [...] Read more.

The common European adder, Vipera berus berus, is a medically relevant species, which is widely distributed in Russia and thus, is responsible for most snakebite accidents in Russia. We have investigated the toxic and enzymatic activities and have determined the proteomic composition of its venom. Phospholipases A₂ (PLA₂, 25.3% of the venom proteome), serine proteinases (SVSP, 16.2%), metalloproteinases (SVMP, 17.2%), vasoactive peptides (bradykinin-potentiating peptides (BPPs), 9.5% and C-type natriuretic peptides (C-NAP, 7.8%), cysteine-rich secretory protein (CRISP, 8%) and L-amino acid oxidase (LAO, 7.3%) represent the major toxin classes found in V. b. berus (Russia) venom. This study was also designed to assess the in vivo and in vitro preclinical efficacy of the Russian Microgen antivenom in neutralizing the main effects of V. b. berus venom. The results show that this antivenom is capable of neutralizing the lethal, hemorrhagic and PLA₂ activities. Third-generation antivenomics was applied to quantify the toxin-recognition landscape and the maximal binding capacity of the antivenom for each component of the venom. The antivenomics analysis revealed that 6.24% of the anti-V. b. berus F(ab’)₂ molecules fraction are toxin-binding antibodies, 60% of which represent clinically relevant antivenom molecules. Full article

(This article belongs to the Special Issue Discovery of Antibodies and Novel Antivenoms against Envenoming)

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12 pages, 1442 KiB

Open AccessEditor’s ChoiceArticle

Rapid Determination of Ochratoxin A in Grape and Its Commodities Based on a Label-Free Impedimetric Aptasensor Constructed by Layer-by-Layer Self-Assembly

by Mina Nan, Yang Bi, Huali Xue, Sulin Xue, Haitao Long, Lumei Pu and Guorui Fu

Toxins 2019, 11(2), 71; https://doi.org/10.3390/toxins11020071 - 28 Jan 2019

Cited by 31 | Viewed by 3841

Abstract

A simple and sensitive label-free impedimetric aptasensor for rapid determination of ochratoxin A (OTA) has been developed, which was based on the combination between thiolated aptamer and gold nanoparticles by layer-by-layer self-assembly. Because of the interaction between aptamer and OTA, the relative normalized [...] Read more.

A simple and sensitive label-free impedimetric aptasensor for rapid determination of ochratoxin A (OTA) has been developed, which was based on the combination between thiolated aptamer and gold nanoparticles by layer-by-layer self-assembly. Because of the interaction between aptamer and OTA, the relative normalized electron-transfer resistance (ΔR_ct) values obtained by electrochemical impedance spectroscopy (EIS) was proportional to the concentration of OTA and showed a good linear relationship from 0.1 to 10.0 ng/mL, with a lower detection limit (0.030 ng/mL) than one-step thiolated DNA aptasensor. The established method was successfully applied to detect and analyze OTA in table wine and grape juice, and the recovery was 90.56%–104.21% when PVP effective removed of phenolic substances. The label-free impedimetric aptasensor was used for rapid detection and quantitation of OTA in the inoculated grapes with the Aspergillus Nigri (H1), and the production of OTA (62.4 μg/kg, 20 μg/kg) far exceeded the maximum levels of 2 μg/kg after inoculation for three days. The developed method exhibited a good specificity, high sensitivity, time-efficient, and it could be applied to detect the OTA concentration in grape and its commodities. Full article

(This article belongs to the Special Issue Advanced Methods for Mycotoxins Detection)

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13 pages, 283 KiB

Open AccessEditor’s ChoiceArticle

The Effects of Endophytic Beauveria bassiana Inoculation on Infestation Level of Planococcus ficus, Growth and Volatile Constituents of Potted Greenhouse Grapevine (Vitis vinifera L.)

by Siphokazi Moloinyane and Felix Nchu

Toxins 2019, 11(2), 72; https://doi.org/10.3390/toxins11020072 - 28 Jan 2019

Cited by 43 | Viewed by 5362

Abstract

Endophytic entomopathogenic fungi are being explored for the management of phytophagous insect pests. The effects of Beauveria bassiana (Hypocreales) inoculation of grape plants on the infestation level of P. ficus, tissue nutrient contents, and growth and volatile constituents of potted grape plants [...] Read more.

Endophytic entomopathogenic fungi are being explored for the management of phytophagous insect pests. The effects of Beauveria bassiana (Hypocreales) inoculation of grape plants on the infestation level of P. ficus, tissue nutrient contents, and growth and volatile constituents of potted grape plants were assessed. Grapevine plants were individually inoculated with a suspension of 1 × 10⁸ conidia mL⁻¹ of B. bassiana by drenching before experimentally infesting each of them with thirty adult females of P. ficus. At four weeks post-treatment, the fungus was re-isolated from leaves of 50% of the fungus-exposed plants. However, no significant difference (p > 0.05) was observed in all the plant growth parameters measured in the fungus-treated and control plants. Plant tissue analysis revealed markedly higher contents of calcium (Ca) and magnesium (Mg) in the leaf tissue of plants exposed to the B. bassiana relative to the control. Gas chromatography mass spectrometry (GC-MS) analyses showed that a significantly (X² = 5.1; p < 0.02) higher number of known anti-insect volatile compounds (nine) were present among fungus treated plants compared to the control plants (five). Naphthalene, which is toxic to insects and humans, was detected only in the volatiles of the fungus-exposed plants. B. bassiana did not have any significant effect on total polyphenol, alkaloid, and flavonoids. Overall, treatment with fungus did not inhibit the infestation by P. ficus. In conclusion, these findings shed light on some of the mechanisms involved in endophytic fungus-plant-insect interactions. Full article

(This article belongs to the Special Issue Fungal Infestations in Humans, Animals, Crops)

10 pages, 1329 KiB

Open AccessEditor’s ChoiceArticle

Aptamer-Based Fluorometric Ochratoxin A Assay Based on Photoinduced Electron Transfer

by Han Zhao, Xinying Xiang, Mingjian Chen and Changbei Ma

Toxins 2019, 11(2), 65; https://doi.org/10.3390/toxins11020065 - 24 Jan 2019

Cited by 29 | Viewed by 4182

Abstract

This study describes a novel quencher-free fluorescent method for ochratoxin A (OTA) detection based on the photoinduced electron transfer (PIET) between guanine and fluorophore. In the absence of OTA, carboxyfluorescein (FAM)-labeled aptamer can partly hybridize with the complementary strand of OTA aptamer (OTA-cAPT), [...] Read more.

This study describes a novel quencher-free fluorescent method for ochratoxin A (OTA) detection based on the photoinduced electron transfer (PIET) between guanine and fluorophore. In the absence of OTA, carboxyfluorescein (FAM)-labeled aptamer can partly hybridize with the complementary strand of OTA aptamer (OTA-cAPT), which contains four guanines at its 3′-end. As a result, the fluorescence of FAM is quenched due to PIET and stacked guanines. In the presence of OTA, FAM-labeled OTA aptamer can bind specifically to OTA, and thereby the high fluorescence intensity of the dye can be maintained. Under the optimal conditions, the method had a detection limit of 1.3 nM. In addition, the method we proposed is highly sensitive and specific for OTA. Furthermore, the method was proven to be reliable based on its successful application in the detection of OTA in red wine samples. Therefore, this promising, facile, and quencher-free method may be applied to detect other toxins by using other appropriate aptamers. Full article

(This article belongs to the Special Issue Advanced Methods for Mycotoxins Detection)

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17 pages, 4265 KiB

Open AccessEditor’s ChoiceArticle

Functional Analysis of FgNahG Clarifies the Contribution of Salicylic Acid to Wheat (Triticum aestivum) Resistance against Fusarium Head Blight

by Peng-Fei Qi, Ya-Zhou Zhang, Cai-Hong Liu, Qing Chen, Zhen-Ru Guo, Yan Wang, Bin-Jie Xu, Yun-Feng Jiang, Ting Zheng, Xi Gong, Cui-Hua Luo, Wang Wu, Li Kong, Mei Deng, Jian Ma, Xiu-Jin Lan, Qian-Tao Jiang, Yu-Ming Wei, Ji-Rui Wang and You-Liang Zheng

Toxins 2019, 11(2), 59; https://doi.org/10.3390/toxins11020059 - 22 Jan 2019

Cited by 37 | Viewed by 5525

Abstract

Salicylic acid (SA) is a key defense hormone associated with wheat resistance against Fusarium head blight, which is a severe disease mainly caused by Fusarium graminearum. Although F. graminearum can metabolize SA, it remains unclear how this metabolic activity affects the wheat– [...] Read more.

Salicylic acid (SA) is a key defense hormone associated with wheat resistance against Fusarium head blight, which is a severe disease mainly caused by Fusarium graminearum. Although F. graminearum can metabolize SA, it remains unclear how this metabolic activity affects the wheat–F. graminearum interaction. In this study, we identified a salicylate hydroxylase gene (FG05_08116; FgNahG) in F. graminearum. This gene encodes a protein that catalyzes the conversion of SA to catechol. Additionally, FgNahG was widely distributed within hyphae. Disrupting the FgNahG gene (ΔFgNahG) led to enhanced sensitivity to SA, increased accumulation of SA in wheat spikes during the early infection stage and inhibited development of head blight symptoms. However, FgNahG did not affect mycotoxin production. Re-introducing a functional FgNahG gene into the ΔFgNahG mutant recovered the wild-type phenotype. Moreover, the expression of FgNahG in transgenic Arabidopsis thaliana decreased the SA concentration and the resistance of leaves to F. graminearum. These results indicate that the endogenous SA in wheat influences the resistance against F. graminearum. Furthermore, the capacity to metabolize SA is an important factor affecting the ability of F. graminearum to infect wheat plants. Full article

(This article belongs to the Special Issue Recent Advances in Fusarium Research)

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11 pages, 3361 KiB

Open AccessEditor’s ChoiceArticle

Simultaneous Lateral Flow Immunoassay for Multi-Class Chemical Contaminants in Maize and Peanut with One-Stop Sample Preparation

by Du Wang, Jianguo Zhu, Zhaowei Zhang, Qi Zhang, Wen Zhang, Li Yu, Jun Jiang, Xiaomei Chen, Xuefang Wang and Peiwu Li

Toxins 2019, 11(1), 56; https://doi.org/10.3390/toxins11010056 - 20 Jan 2019

Cited by 51 | Viewed by 4691

Abstract

Multi-class chemical contaminants, such as pesticides and mycotoxins, are recognized as the major risk factors in agro products. It is thus necessary to develop rapid and simple sensing methods to fulfill the on-site monitoring of multi-class chemical contaminants with different physicochemical properties. Herein, [...] Read more.

Multi-class chemical contaminants, such as pesticides and mycotoxins, are recognized as the major risk factors in agro products. It is thus necessary to develop rapid and simple sensing methods to fulfill the on-site monitoring of multi-class chemical contaminants with different physicochemical properties. Herein, a lateral flow immunoassay via time-resolved fluorescence was developed for the rapid, on-site, simultaneous, and quantitative sensing aflatoxin B₁ (AFB₁), zearalenone (ZEA), and chlorothalonil (CTN) in maize and peanut. The sample preparation was optimized to a single step, combining the grinding and extraction. Under optimal conditions, the sensing method lowered the limits of detection (LOD) to 0.16, 0.52, and 1.21 µg/kg in maize and 0.18, 0.57, and 1.47 µg/kg in peanut with an analytical range of 0.48–20, 1.56–200, and 3.63–300 µg/kg for AFB₁, ZEA and CTN, respectively. The protocol could be completed within 15 min, including sample preparation and lateral flow immunoassay. The recovery range was 83.24–110.80%. An excellent correlation was observed between this approach and high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) for mycotoxins and gas chromatography-tandem mass spectrometry (GC-MS/MS) for pesticide in maize and peanut. This work could be applied in on-site multi-class sensing for food safety. Full article

(This article belongs to the Special Issue Advanced Methods for Mycotoxins Detection)

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16 pages, 2819 KiB

Open AccessEditor’s ChoiceArticle

Gut Microbiota Profiling of Aflatoxin B1-Induced Rats Treated with Lactobacillus casei Shirota

by Winnie-Pui-Pui Liew, Sabran Mohd-Redzwan and Leslie Thian Lung Than

Toxins 2019, 11(1), 49; https://doi.org/10.3390/toxins11010049 - 17 Jan 2019

Cited by 34 | Viewed by 6110

Abstract

Aflatoxin B1 (AFB1) is a ubiquitous carcinogenic food contaminant. Gut microbiota is of vital importance for the host’s health, regrettably, limited studies have reported the effects of xenobiotic toxins towards gut microbiota. Thus, the present study aims to investigate the interactions between AFB1 [...] Read more.

Aflatoxin B1 (AFB1) is a ubiquitous carcinogenic food contaminant. Gut microbiota is of vital importance for the host’s health, regrettably, limited studies have reported the effects of xenobiotic toxins towards gut microbiota. Thus, the present study aims to investigate the interactions between AFB1 and the gut microbiota. Besides, an AFB1-binding microorganism, Lactobacillus casei Shirota (Lcs) was tested on its ability to ameliorate the changes on gut microbiota induced by AFB1. The fecal contents of three groups of rats included an untreated control group, an AFB1 group, as well as an Lcs + AFB1 group, were analyzed. Using the MiSeq platform, the PCR products of 16S rDNA gene extracted from the feces were subjected to next-generation sequencing. The alpha diversity index (Shannon) showed that the richness of communities increased significantly in the Lcs + AFB1 group compared to the control and AFB1 groups. Meanwhile, beta diversity indices demonstrated that AFB1 group significantly deviated from the control and Lcs + AFB1 groups. AFB1-exposed rats were especially high in Alloprevotella spp. abundance. Such alteration in the bacterial composition might give an insight on the interactions of AFB1 towards gut microbiota and how Lcs plays its role in detoxification of AFB1. Full article

(This article belongs to the Special Issue Mycotoxin Exposure and Related Diseases)

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15 pages, 2534 KiB

Open AccessEditor’s ChoiceArticle

Mass Spectrometry Analysis and Biological Characterization of the Predatory Ant Odontomachus monticola Venom and Venom Sac Components

by Naoki Tani, Kohei Kazuma, Yukio Ohtsuka, Yasushi Shigeri, Keiichi Masuko, Katsuhiro Konno and Hidetoshi Inagaki

Toxins 2019, 11(1), 50; https://doi.org/10.3390/toxins11010050 - 17 Jan 2019

Cited by 15 | Viewed by 4821

Abstract

We previously identified 92 toxin-like peptides and proteins, including pilosulin-like peptides 1–6 from the predatory ant Odontomachus monticola, by transcriptome analysis. Here, to further characterize venom components, we analyzed the venom and venom sac extract by ESI-MS/MS with or without trypsin digestion [...] Read more.

We previously identified 92 toxin-like peptides and proteins, including pilosulin-like peptides 1–6 from the predatory ant Odontomachus monticola, by transcriptome analysis. Here, to further characterize venom components, we analyzed the venom and venom sac extract by ESI-MS/MS with or without trypsin digestion and reducing agent. As the low-molecular-mass components, we found amino acids (leucine/isoleucine, phenylalanine, and tryptophan) and biogenic amines (histamine and tyramine) in the venom and venom sac extract. As the higher molecular mass components, we found peptides and proteins such as pilosulin-like peptides, phospholipase A₂s, hyaluronidase, venom dipeptidyl peptidases, conotoxin-like peptide, and icarapin-like peptide. In addition to pilosulin-like peptides 1–6, we found three novel pilosulin-like peptides that were overlooked by transcriptome analysis. Moreover, pilosulin-like peptides 1–6 were chemically synthesized, and some of them displayed antimicrobial, hemolytic, and histamine-releasing activities. Full article

(This article belongs to the Special Issue Arthropod Venom Components and Their Potential Usage)

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18 pages, 2322 KiB

Open AccessEditor’s ChoiceArticle

Botulinum Neurotoxin Therapy for Lingual Dystonia Using an Individualized Injection Method Based on Clinical Features

by Kazuya Yoshida

Toxins 2019, 11(1), 51; https://doi.org/10.3390/toxins11010051 - 17 Jan 2019

Cited by 31 | Viewed by 16001

Abstract

Lingual dystonia is a debilitating type of oromandibular dystonia characterized by involuntary, often task-specific, contractions of the tongue muscle activated by speaking or eating. Botulinum neurotoxin (BoNT) has been used to treat lingual dystonia; however, it is known to cause serious complications, such [...] Read more.

Lingual dystonia is a debilitating type of oromandibular dystonia characterized by involuntary, often task-specific, contractions of the tongue muscle activated by speaking or eating. Botulinum neurotoxin (BoNT) has been used to treat lingual dystonia; however, it is known to cause serious complications, such as dysphasia and aspiration. The purpose of this study was to evaluate the efficacy and adverse effects of individualized BoNT therapy for lingual dystonia. One-hundred-and-seventy-two patients (102 females and 70 males, mean age: 46.2 years) with lingual dystonia were classified into four subtypes based on symptoms of involuntary tongue movements: protrusion (68.6%), retraction (16.9%), curling (7.6%), and laterotrusion (7.0%). Patients were treated with BoNT injection into the genioglossus and/or intrinsic muscles via individualized submandibular and/or intraoral routes. Results were compared before and after BoNT therapy. Botulinum neurotoxin was injected in 136 patients (mean: 4.8 injections). Clinical sub-scores (mastication, speech, pain, and discomfort) in a disease-specific rating scale were reduced significantly (p < 0.001) after administration. Comprehensive improvement after BoNT injection, assessed using the rating scale, was 77.6%. The curling type (81.9%) showed the greatest improvement, while the retraction type showed the least improvement (67.9%). Mild and transient dysphasia occurred in 12.5% of patients (3.7% of total injections) but disappeared spontaneously within several days to two weeks. No serious side effects were observed. With careful diagnosis of subtypes and a detailed understanding of lingual muscle anatomy, individualized BoNT injection into dystonic lingual muscles can be effective and safe. Full article

(This article belongs to the Special Issue Botulinum Toxin Treatment of Movement Disorders)

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23 pages, 916 KiB

Open AccessEditor’s ChoiceArticle

Regional Sub-Saharan Africa Total Diet Study in Benin, Cameroon, Mali and Nigeria Reveals the Presence of 164 Mycotoxins and Other Secondary Metabolites in Foods

by Luc Ingenbleek, Michael Sulyok, Abimbola Adegboye, Sètondji Epiphane Hossou, Abdoulaye Zié Koné, Awoyinka Dada Oyedele, Chabi Sika K. J. Kisito, Yara Koreissi Dembélé, Sara Eyangoh, Philippe Verger, Jean-Charles Leblanc, Bruno Le Bizec and Rudolf Krska

Toxins 2019, 11(1), 54; https://doi.org/10.3390/toxins11010054 - 17 Jan 2019

Cited by 52 | Viewed by 8766

Abstract

In the framework of the first multi-centre Sub-Saharan Africa Total Diet Study (SSA-TDS), 2328 commonly consumed foods were purchased, prepared as consumed and pooled into 194 composite samples of cereals, tubers, legumes, vegetables, nuts and seeds, dairy, oils, beverages and miscellaneous. Those core [...] Read more.

In the framework of the first multi-centre Sub-Saharan Africa Total Diet Study (SSA-TDS), 2328 commonly consumed foods were purchased, prepared as consumed and pooled into 194 composite samples of cereals, tubers, legumes, vegetables, nuts and seeds, dairy, oils, beverages and miscellaneous. Those core foods were tested for mycotoxins and other fungal, bacterial and plant secondary metabolites by liquid chromatography, coupled with tandem mass spectrometry. The highest aflatoxin concentrations were quantified in peanuts, peanut oil and maize. The mean concentration of the sum of aflatoxins AFB1, AFB2, AFG1 and AFG2 (AF_tot) in peanut samples (56.4 µg/kg) exceeded EU (4 µg/kg) and Codex (15 µg/kg) standards. The AF_tot concentration (max: 246.0 µg/kg) was associated with seasonal and geographic patterns and comprised, on average, 80% AFB1, the most potent aflatoxin. Although ochratoxin A concentrations rarely exceeded existing Codex standards, it was detected in unregulated foods. One palm oil composite sample contained 98 different metabolites, including 35.4 µg/kg of ochratoxin A. In total, 164 different metabolites were detected, with unspecific metabolites like asperglaucide, cyclo(L-pro-L-val), cyclo (L-pro-L-tyr), flavoglaucin, emodin and tryptophol occurring in more than 50% of composite samples. Aflatoxin B1 (AFB1), fumonisin B1 (FB1), sterigmatocystin (STC), ochratoxin A (OTA), citrinin (CIT) and many other secondary fungal metabolites are frequent co-contaminants in staple foods, such as maize and sorghum. Populations from North Cameroon and from Benin may, therefore, suffer chronic and simultaneous exposure to AFB1, FB1, STC, OTA and CIT, which are prevalent in their diet. Full article

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

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11 pages, 1156 KiB

Open AccessEditor’s ChoiceArticle

Differences in Dialysis Efficacy Have Limited Effects on Protein-Bound Uremic Toxins Plasma Levels over Time

by Detlef H. Krieter, Simon Kerwagen, Marieke Rüth, Horst-Dieter Lemke and Christoph Wanner

Toxins 2019, 11(1), 47; https://doi.org/10.3390/toxins11010047 - 16 Jan 2019

Cited by 27 | Viewed by 4124

Abstract

The protein-bound uremic toxins para-cresyl sulfate (pCS) and indoxyl sulfate (IS) are associated with cardiovascular disease in chronic renal failure, but the effect of different dialysis procedures on their plasma levels over time is poorly studied. The present prospective, randomized, cross-over trial tested [...] Read more.

The protein-bound uremic toxins para-cresyl sulfate (pCS) and indoxyl sulfate (IS) are associated with cardiovascular disease in chronic renal failure, but the effect of different dialysis procedures on their plasma levels over time is poorly studied. The present prospective, randomized, cross-over trial tested dialysis efficacy and monitored pre-treatment pCS and IS concentrations in 15 patients on low-flux and high-flux hemodialysis and high-convective volume postdilution hemodiafiltration over six weeks each. Although hemodiafiltration achieved by far the highest toxin removal, only the mean total IS level was decreased at week three (16.6 ± 12.1 mg/L) compared to baseline (18.9 ± 13.0 mg/L, p = 0.027) and to low-flux dialysis (20.0 ± 12.7 mg/L, p = 0.021). At week six, the total IS concentration in hemodiafiltration reached the initial values again. Concentrations of free IS and free and total pCS remained unaltered. Highest beta₂-microglobulin elimination in hemodiafiltration (p < 0.001) led to a persistent decrease of the plasma levels at week three and six (each p < 0.001). In contrast, absent removal in low-flux dialysis resulted in rising beta₂-microglobulin concentrations (p < 0.001). In conclusion, this trial demonstrated that even large differences in instantaneous protein-bound toxin removal by current extracorporeal dialysis techniques may have only limited impact on IS and pCS plasma levels in the longer term. Full article

(This article belongs to the Section Uremic Toxins)

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17 pages, 3362 KiB

Open AccessEditor’s ChoiceArticle

The Individual and Combined Effects of the Cyanotoxins, Anatoxin-a and Microcystin-LR, on the Growth, Toxin Production, and Nitrogen Fixation of Prokaryotic and Eukaryotic Algae

by Mathias Ahii Chia, Benjamin J. Kramer, Jennifer G. Jankowiak, Maria do Carmo Bittencourt-Oliveira and Christopher J. Gobler

Toxins 2019, 11(1), 43; https://doi.org/10.3390/toxins11010043 - 15 Jan 2019

Cited by 36 | Viewed by 6041

Abstract

Globally, eutrophication and warming of aquatic ecosystems has increased the frequency and intensity of cyanobacterial blooms and their associated toxins, with the simultaneous detection of multiple cyanotoxins often occurring. Despite the co-occurrence of cyanotoxins such as microcystins and anatoxin-a (ATX) in water bodies, [...] Read more.

Globally, eutrophication and warming of aquatic ecosystems has increased the frequency and intensity of cyanobacterial blooms and their associated toxins, with the simultaneous detection of multiple cyanotoxins often occurring. Despite the co-occurrence of cyanotoxins such as microcystins and anatoxin-a (ATX) in water bodies, their effects on phytoplankton communities are poorly understood. The individual and combined effects of microcystin-LR (MC-LR) and ATX on the cyanobacteria Microcystis spp., and Anabaena variabilis (a.k.a. Trichormus variabilis), and the chlorophyte, Selenastrum capricornutum were investigated in the present study. Cell density, chlorophyll-a content, and the maximum quantum efficiency of photosystem II (Fv/Fm) of Microcystis cells were generally lowered after exposure to ATX or MC-LR, while the combined treatment with MC-LR and ATX synergistically reduced the chlorophyll-a concentration of Microcystis strain LE-3. Intracellular levels of microcystin in Microcystis LE-3 significantly increased following exposure to MC-LR + ATX. The maximum quantum efficiency of photosystem II of Anabaena strain UTEX B377 declined during exposure to the cyanotoxins. Nitrogen fixation by Anabaena UTEX B377 was significantly inhibited by exposure to ATX, but was unaffected by MC-LR. In contrast, the combination of both cyanotoxins (MC-LR + ATX) caused a synergistic increase in the growth of S. capricornutum. While the toxins caused an increase in the activity of enzymes that scavenge reactive oxygen species in cyanobacteria, enzyme activity was unchanged or decreased in S. capricornutum. Collectively this study demonstrates that MC-LR and ATX can selectively promote and inhibit the growth and performance of green algae and cyanobacteria, respectively, and that the combined effect of these cyanotoxins was often more intense than their individual effects on some strains. This suggests that the release of multiple cyanotoxins in aquatic ecosystems, following the collapse of blooms, may influence the succession of plankton communities. Full article

(This article belongs to the Special Issue Harmful Algal Bloom Dynamics)

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18 pages, 2079 KiB

Open AccessEditor’s ChoiceArticle

Spatial and Temporal Variation in Paralytic Shellfish Toxin Production by Benthic Microseira (Lyngbya) wollei in a Freshwater New York Lake

by Zacharias J. Smith, Robbie M. Martin, Bofan Wei, Steven W. Wilhelm and Gregory L. Boyer

Toxins 2019, 11(1), 44; https://doi.org/10.3390/toxins11010044 - 15 Jan 2019

Cited by 27 | Viewed by 6571

Abstract

Butterfield Lake is a mesotrophic lake in New York State where residents and pets have experienced unexplained health issues. Microseira wollei (basionym Lyngbya wollei) was found at two of 15 sites in Butterfield Lake and analyzed for microcystins, anatoxins, cylindrospermopsins, and paralytic [...] Read more.

Butterfield Lake is a mesotrophic lake in New York State where residents and pets have experienced unexplained health issues. Microseira wollei (basionym Lyngbya wollei) was found at two of 15 sites in Butterfield Lake and analyzed for microcystins, anatoxins, cylindrospermopsins, and paralytic shellfish poisoning toxins (PSTs). Only PSTs and trace levels of anatoxin-a were detected in these samples. This is the first published report of PSTs within a New York State lake. To evaluate the environmental and temporal drivers leading to the observed toxicity, PST content at the two sites was examined in detail. There were distinct differences in the total PST content, filament nutrient, filament chlorophyll, and relationship to environmental drivers between the sites, as well as distinct differences in the total PST content measured using different analytical techniques. A multivariate model containing site, temperature, and filament chlorophyll explained 85% of the variation in PSTs observed over the growing season. This work emphasizes the importance of proper site selection and choice of analytical technique in the development of monitoring programs to protect lake users from the occurrence of benthic cyanobacteria toxins. Full article

(This article belongs to the Special Issue Paralytic Shellfish Toxins)

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14 pages, 3019 KiB

Open AccessEditor’s ChoiceArticle

Autophagy and Apoptosis Interact to Modulate T-2 Toxin-Induced Toxicity in Liver Cells

by Jing Wu, Yu Zhou, Zhihang Yuan, Jine Yi, Jingshu Chen, Naidong Wang and Yanan Tian

Toxins 2019, 11(1), 45; https://doi.org/10.3390/toxins11010045 - 15 Jan 2019

Cited by 58 | Viewed by 6360

Abstract

T-2 toxin is a mycotoxin generated by Fusarium species which has been shown to be highly toxic to human and animals. T-2 toxin induces apoptosis in various tissues/organs. Apoptosis and autophagy are two closely interconnected processes, which are important for maintaining physiological homeostasis [...] Read more.

T-2 toxin is a mycotoxin generated by Fusarium species which has been shown to be highly toxic to human and animals. T-2 toxin induces apoptosis in various tissues/organs. Apoptosis and autophagy are two closely interconnected processes, which are important for maintaining physiological homeostasis as well as pathogenesis. Here, for the first time, we demonstrated that T-2 toxins induce autophagy in human liver cells (L02). We demonstrated that T-2 toxin induce acidic vesicular organelles formation, concomitant with the alterations in p62/SQSTM1 and LC3-phosphatidylethanolamine conjugate (LC3-II) and the enhancement of the autophagic flux. Using mRFP-GFP-LC3 by lentiviral transduction, we showed T-2 toxin-mediated lysosomal fusion and the formation of autophagosomes in L02 cells. The formation of autophagosomes was further confirmed by transmission electron microcopy. While T-2 toxin induced both autophagy and apoptosis, autophagy appears to be a leading event in the response to T-2 toxin treatment, reflecting its protective role in cells against cellular damage. Activating autophagy by rapamycin (RAPA) inhibited apoptosis, while suppressing autophagy by chloroquine greatly enhanced the T-2 toxin-induced apoptosis, suggesting the crosstalk between autophagy and apoptosis. Taken together, these results indicate that autophagy plays a role in protecting cells from T-2 toxin-induced apoptosis suggesting that autophagy may be manipulated for the alleviation of toxic responses induced by T-2 toxin. Full article

(This article belongs to the Special Issue Dietary Mycotoxin Exposure: Emerging Risks to Human Health)

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21 pages, 5601 KiB

Open AccessEditor’s ChoiceArticle

Mesoscale Dynamics and Niche Segregation of Two Dinophysis Species in Galician-Portuguese Coastal Waters

by Patricio A. Díaz, Beatriz Reguera, Teresa Moita, Isabel Bravo, Manuel Ruiz-Villarreal and Santiago Fraga

Toxins 2019, 11(1), 37; https://doi.org/10.3390/toxins11010037 - 14 Jan 2019

Cited by 22 | Viewed by 4108

Abstract

Blooms of Dinophysis acuminata occur every year in Galicia (northwest Spain), between spring and autumn. These blooms contaminate shellfish with lipophilic toxins and cause lengthy harvesting bans. They are often followed by short-lived blooms of Dinophysis acuta, associated with northward longshore transport, [...] Read more.

Blooms of Dinophysis acuminata occur every year in Galicia (northwest Spain), between spring and autumn. These blooms contaminate shellfish with lipophilic toxins and cause lengthy harvesting bans. They are often followed by short-lived blooms of Dinophysis acuta, associated with northward longshore transport, at the end of the upwelling season. During the summers of 1989 and 1990, dense blooms of D. acuta developed in situ, initially co-occurring with D. acuminata and later with the paralytic shellfish toxin-producer Gymnodinium catenatum. Unexplored data from three cruises carried out before, during, and following autumn blooms (13–14, 27–28 September and 11–12 October) in 1990 showed D. acuta distribution in shelf waters within the 50 m and 130 m isobaths, delimited by the upwelling front. A joint review of monitoring data from Galicia and Portugal provided a mesoscale view of anomalies in SST and other hydroclimatic factors associated with a northward displacement of the center of gravity of D. acuta populations. At the microscale, re-examination of the vertical segregation of cell maxima in the light of current knowledge, improved our understanding of niche differentiation between the two species of Dinophysis. Results here improve local transport models and forecast of Dinophysis events, the main cause of shellfish harvesting bans in the most important mussel production area in Europe. Full article

(This article belongs to the Special Issue Dinophysis Toxins: Distribution, Fate in Shellfish and Impacts)

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15 pages, 1261 KiB

Open AccessEditor’s ChoiceArticle

Combined Effect of Light and Temperature on the Production of Saxitoxins in Cylindrospermopsis raciborskii Strains

by Marcella C. B. Mesquita, Miquel Lürling, Fabiane Dorr, Ernani Pinto and Marcelo M. Marinho

Toxins 2019, 11(1), 38; https://doi.org/10.3390/toxins11010038 - 14 Jan 2019

Cited by 24 | Viewed by 5377

Abstract

Cylindrospermopsis raciborskii is a potentially toxic freshwater cyanobacterium that can tolerate a wide range of light and temperature. Due to climatic changes, the interaction between light and temperature is studied in aquatic systems, but no study has addressed the effect of both variables [...] Read more.

Cylindrospermopsis raciborskii is a potentially toxic freshwater cyanobacterium that can tolerate a wide range of light and temperature. Due to climatic changes, the interaction between light and temperature is studied in aquatic systems, but no study has addressed the effect of both variables on the saxitoxins production. This study evaluated the combined effect of light and temperature on saxitoxins production and cellular quota in C. raciborskii. Experiments were performed with three C. raciborskii strains in batch cultures under six light intensities (10, 40, 60, 100, 150, and 500 μmol of photons m⁻² s⁻¹) and four temperatures (15, 20, 25, and 30 °C). The growth of C. raciborskii strains was limited at lower temperatures and the maximum growth rates were obtained under higher light combined with temperatures equal or above 20 °C, depending on the strain. In general, growth was highest at 30 °C at the lower light intensities and equally high at 25 °C and 30 °C under higher light. Highest saxitoxins concentration and cell-quota occurred at 25 °C under high light intensities, but were much lower at 30 °C. Hence, increased temperatures combined with sufficient light will lead to higher C. raciborskii biomass, but blooms could become less toxic in tropical regions. Full article

(This article belongs to the Special Issue Paralytic Shellfish Toxins)

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20 pages, 6252 KiB

Open AccessEditor’s ChoiceArticle

Osmotic-Adaptation Response of sakA/hogA Gene to Aflatoxin Biosynthesis, Morphology Development and Pathogenicity in Aspergillus flavus

by Elisabeth Tumukunde, Ding Li, Ling Qin, Yu Li, Jiaojiao Shen, Shihua Wang and Jun Yuan

Toxins 2019, 11(1), 41; https://doi.org/10.3390/toxins11010041 - 14 Jan 2019

Cited by 27 | Viewed by 4359

Abstract

Aspergillus flavus is one of the fungi from the big family of Aspergillus genus and it is capable of colonizing a large number of seed/crops and living organisms such as animals and human beings. SakA (also called hogA/hog1) is an integral [...] Read more.

Aspergillus flavus is one of the fungi from the big family of Aspergillus genus and it is capable of colonizing a large number of seed/crops and living organisms such as animals and human beings. SakA (also called hogA/hog1) is an integral part of the mitogen activated protein kinase signal of the high osmolarity glycerol pathway. In this study, the AfsakA gene was deleted (∆AfsakA) then complemented (∆AfsakA::AfsakA) using homologous recombination and the osmotic stress was induced by 1.2 mol/L D-sorbital and 1.2 mol/L sodium chloride. The result showed that ∆AfsakA mutant caused a significant influence on conidial formation compared to wild-type and ∆AfsakA::AfsakA strains. It was also found that AfsakA responds to both the osmotic stress and the cell wall stress. In the absence of osmotic stress, ∆AfsakA mutant produced more sclerotia in contrast to other strains, whereas all strains failed to generate sclerotia under osmotic stress. Furthermore, the deletion of AfsakA resulted in the increase of Aflatoxin B₁ production compared to other strains. The virulence assay on both maize kernel and peanut seeds showed that ∆AfsakA strain drastically produced more conidia and Aflatoxin B₁ than wild-type and complementary strains. AfSakA-mCherry was located to the cytoplasm in the absence of osmotic stress, while it translocated to the nucleus upon exposure to the osmotic stimuli. This study provides new insights on the development and evaluation of aflatoxin biosynthesis and also provides better understanding on how to prevent Aspergillus infections which would be considered the first step towards the prevention of the seeds damages caused by A. flavus. Full article

(This article belongs to the Section Mycotoxins)

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13 pages, 1067 KiB

Open AccessEditor’s ChoiceArticle

Effect of Compound Probiotics and Mycotoxin Degradation Enzymes on Alleviating Cytotoxicity of Swine Jejunal Epithelial Cells Induced by Aflatoxin B₁ and Zearalenone

by Weiwei Huang, Juan Chang, Ping Wang, Chaoqi Liu, Qingqiang Yin, Andong Song, Tianzeng Gao, Xiaowei Dang and Fushan Lu

Toxins 2019, 11(1), 12; https://doi.org/10.3390/toxins11010012 - 10 Jan 2019

Cited by 33 | Viewed by 5313

Abstract

Zearalenone (ZEA) and aflatoxin B₁ (AFB₁) are two main kinds of mycotoxins widely existing in grain and animal feed that cause a lot of economic loss and health problems for animals and humans. In order to alleviate the cytotoxic effects [...] Read more.

Zearalenone (ZEA) and aflatoxin B₁ (AFB₁) are two main kinds of mycotoxins widely existing in grain and animal feed that cause a lot of economic loss and health problems for animals and humans. In order to alleviate the cytotoxic effects of AFB₁ and ZEA on swine jejunal epithelial cells (IPEC-J2), the combination of a cell-free supernatant of compound probiotics (CFSCP) with mycotoxin degradation enzymes (MDEs) from Aspergillus oryzae was tested. The results demonstrated that coexistence of AFB₁ and ZEA had synergetic toxic effects on cell viability. The cell viability was decreased with mycotoxin concentrations increasing, but increased with incubation time extension. The necrotic cell rates were increased when 40 µg/L AFB₁ and/or 500 µg/L ZEA were added, but the addition of CFSCP + MDE suppressed the necrotic effects of AFB₁ + ZEA. The viable cell rates were decreased when AFB₁ and/or ZEA were added: However, the addition of CFSCP + MDE recovered them. The relative mRNA abundances of Bcl-2, occludin, and ZO-1 genes were significantly upregulated, while Bax, caspase-3, GLUT2, ASCT2, PepT1, and IL6 genes were significantly downregulated by CFSCP + MDE addition, compared to the groups containing 40 µg/L AFB₁ and 500 µg/L ZEA. This research provided an effective strategy in alleviating mycotoxin cytotoxicity and keeping normal intestinal cell structure and animal health. Full article

(This article belongs to the Special Issue Biological Control and Post-Harvest Detoxification of Mycotoxins as Strategies to Reduce the Impact of Mycotoxins)

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14 pages, 893 KiB

Open AccessEditor’s ChoiceArticle

Assessment of Toxigenic Fusarium Species and Their Mycotoxins in Brewing Barley Grains

by Karim C. Piacentini, Liliana O. Rocha, Geovana D. Savi, Lorena Carnielli-Queiroz, Livia De Carvalho Fontes and Benedito Correa

Toxins 2019, 11(1), 31; https://doi.org/10.3390/toxins11010031 - 10 Jan 2019

Cited by 37 | Viewed by 4942

Abstract

Fusarium species threaten yield and quality of cereals worldwide due to their ability to produce mycotoxins and cause plant diseases. Trichothecenes and zearalenone are the most economically significant mycotoxins and are of particular concern in barley, maize and wheat. For this reason, the [...] Read more.

Fusarium species threaten yield and quality of cereals worldwide due to their ability to produce mycotoxins and cause plant diseases. Trichothecenes and zearalenone are the most economically significant mycotoxins and are of particular concern in barley, maize and wheat. For this reason, the aim of this study was to characterize the Fusarium isolates from brewing barley and to assess deoxynivalenol and zearalenone contamination in grains. Characterization of the Fusarium strains was carried out by the phylogeny based on two loci (EF-1α and RPB2). Mycotoxin detection and quantification were performed by LC-MS. The results show that Fusarium was the predominant genus. Phylogenetic study demonstrated that the majority of the strains clustered within the Fusarium sambucinum species complex followed by the Fusarium tricinctum species complex. The results revealed high incidence of deoxynivalenol (DON) and zearalenone (ZEA) contamination (90.6% and 87.5%, respectively). It was observed that 86% of the samples contaminated with ZEA were above the limits set by the EU and Brazilian regulations. These results may highlight the importance of controlling Fusarium toxins in barley, mainly because of its use in the brewing industry and the resistance of various mycotoxins to food processing treatments. Full article

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

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17 pages, 2425 KiB

Open AccessEditor’s ChoiceArticle

Generation of a Broadly Cross-Neutralizing Antibody Fragment against Several Mexican Scorpion Venoms

by Lidia Riaño-Umbarila, Ilse V. Gómez-Ramírez, Luis M. Ledezma-Candanoza, Timoteo Olamendi-Portugal, Everardo Remi Rodríguez-Rodríguez, Guillermo Fernández-Taboada, Lourival D. Possani and Baltazar Becerril

Toxins 2019, 11(1), 32; https://doi.org/10.3390/toxins11010032 - 10 Jan 2019

Cited by 25 | Viewed by 4448

Abstract

The recombinant antibody fragments generated against the toxic components of scorpion venoms are considered a promising alternative for obtaining new antivenoms for therapy. Using directed evolution and site-directed mutagenesis, it was possible to generate a human single-chain antibody fragment with a broad cross-reactivity [...] Read more.

The recombinant antibody fragments generated against the toxic components of scorpion venoms are considered a promising alternative for obtaining new antivenoms for therapy. Using directed evolution and site-directed mutagenesis, it was possible to generate a human single-chain antibody fragment with a broad cross-reactivity that retained recognition for its original antigen. This variant is the first antibody fragment that neutralizes the effect of an estimated 13 neurotoxins present in the venom of nine species of Mexican scorpions. This single antibody fragment showed the properties of a polyvalent antivenom. These results represent a significant advance in the development of new antivenoms against scorpion stings, since the number of components would be minimized due to their broad cross-neutralization capacity, while at the same time bypassing animal immunization. Full article

(This article belongs to the Special Issue Discovery of Antibodies and Novel Antivenoms against Envenoming)

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16 pages, 3093 KiB

Open AccessEditor’s ChoiceArticle

The Impact of Dietary Grape Seed Meal on Healthy and Aflatoxin B1 Afflicted Microbiota of Pigs after Weaning

by Iulian A. Grosu, Gina C. Pistol, Ionelia Taranu and Daniela E. Marin

Toxins 2019, 11(1), 25; https://doi.org/10.3390/toxins11010025 - 8 Jan 2019

Cited by 30 | Viewed by 4057

Abstract

The study investigated the effect of grape seed (GS) meal, aflatoxin (AFB1), or their combination on the large intestine microbiota of weanling piglets. Twenty-four piglets were allocated into four groups based on diet composition: (1) Control group; (2) AFB1 (320 g/kg feed) group; [...] Read more.

The study investigated the effect of grape seed (GS) meal, aflatoxin (AFB1), or their combination on the large intestine microbiota of weanling piglets. Twenty-four piglets were allocated into four groups based on diet composition: (1) Control group; (2) AFB1 (320 g/kg feed) group; (3) GS group (8% inclusion in the diet); (4) AFB1 + GS group. After 30 days of experiment, the colon content was used for microbiota analyses; after isolation of total bacterial genomic DNA, V3/V4 regions of the 16S rRNA amplicons were sequenced using the Illumina MiSeq platform. The raw sequences were analyzed using the v.1.9.1 QIIME pipeline software. 157 numbers of OTUs were identified among all four dietary groups with 26 of them being prevalent above 0.05% in the total relative abundance. GS and AFB1 increase the relative abundance of phylum Bacteroidetes and Proteobacteria, while decreasing the Firmicutes abundance in a synergic manner as compared with the individual treatments. An additive or synergistic action of the two treatments was identified for Lactobacillus, Prevotella and Campylobacter, while rather an antagonistic effect was observed on Lachnospira. The action mechanisms of aflatoxin B1 and grape seed meal that drive the large intestine microbiota to these changes are not known and need further investigations. Full article

(This article belongs to the Section Mycotoxins)

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16 pages, 2245 KiB

Open AccessEditor’s ChoiceArticle

Factors Associated with Systemic Bleeding in Bothrops Envenomation in a Tertiary Hospital in the Brazilian Amazon

by Sâmella S. Oliveira, Eliane C. Alves, Alessandra S. Santos, João Pedro T. Pereira, Lybia Kássia S. Sarraff, Elizandra F. Nascimento, José Diego De-Brito-Sousa, Vanderson S. Sampaio, Marcus V.G. Lacerda, Jacqueline A.G. Sachett, Ida S. Sano-Martins and Wuelton M. Monteiro

Toxins 2019, 11(1), 22; https://doi.org/10.3390/toxins11010022 - 7 Jan 2019

Cited by 40 | Viewed by 4692

Abstract

Bothrops snakebites usually present systemic bleeding, and the clinical–epidemiological and laboratorial factors associated with the development of this manifestation are not well established. In this study, we assessed the prevalence of Bothrops snakebites with systemic bleeding reported at the Fundação de Medicina Tropical [...] Read more.

Bothrops snakebites usually present systemic bleeding, and the clinical–epidemiological and laboratorial factors associated with the development of this manifestation are not well established. In this study, we assessed the prevalence of Bothrops snakebites with systemic bleeding reported at the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, in Manaus, Amazonas State, Brazil, and the clinical–epidemiological and laboratorial factors associated with systemic bleeding. This is an observational, cross-sectional study carried out between August, 2013 and July, 2016. Patients who developed systemic bleeding on admission or during hospitalization were considered cases, and those with non-systemic bleeding were included in the control group. Systemic bleeding was observed in 63 (15.3%) of the 442 Bothrops snakebites evaluated. Bothrops snakebites mostly occurred in males (78.2%), in rural areas (89.0%) and in the age group of 11 to 30 years old (40.4%). It took most of the patients (59.8%) less than 3 h to receive medical assistance. Unclottable blood (AOR = 3.11 (95% CI = 1.53 to 6.31; p = 0.002)) and thrombocytopenia (AOR = 4.52 (95% CI = 2.03 to 10.09; p < 0.001)) on admission were independently associated with systemic bleeding during hospitalization. These hemostatic disorders on admission increase the chances of systemic bleeding during hospitalization. Prospective studies are needed to clarify the pathophysiology of systemic bleeding in Bothrops snakebites in the Amazon region. Full article

(This article belongs to the Section Animal Venoms)

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15 pages, 1979 KiB

Open AccessEditor’s ChoiceArticle

Grape Seed Proanthocyanidin Extract Alleviates AflatoxinB₁-Induced Immunotoxicity and Oxidative Stress via Modulation of NF-κB and Nrf2 Signaling Pathways in Broilers

by Shahid Ali Rajput, Lvhui Sun, Ni-Ya Zhang, Mahmoud Mohamed Khalil, Zhao Ling, Li Chong, Shuai Wang, Imran Rashid Rajput, Dost Muhammad Bloch, Farhan Anwar Khan, Aftab Shaukat and Desheng Qi

Toxins 2019, 11(1), 23; https://doi.org/10.3390/toxins11010023 - 7 Jan 2019

Cited by 63 | Viewed by 6505

Abstract

Aflatoxin B₁ (AFB₁) is a widely spread mycotoxin contaminates food and feed, causing severe oxidative stress damages and immunotoxicity. Grape seed proanthocyanidin (GSPE), a natural antioxidant with wide range of pharmacological and medicinal properties. The goal of the present study [...] Read more.

Aflatoxin B₁ (AFB₁) is a widely spread mycotoxin contaminates food and feed, causing severe oxidative stress damages and immunotoxicity. Grape seed proanthocyanidin (GSPE), a natural antioxidant with wide range of pharmacological and medicinal properties. The goal of the present study was to investigate the protective effects of GSPE against AFB₁-induced immunotoxicity and oxidative stress via NF-κB and Nrf2 signaling pathways in broiler chickens. For the experiment, 240 one-day old Cobb chicks were allocated into four dietary treatment groups of six replicates (10 birds per replicate): 1. Basal diet (control); 2. Basal diet + AFB₁ 1mg/kg contaminated corn (AFB₁); 3. Basal diet + GSPE 250 mg/kg (GSPE); 4. Basal diet + AFB₁ 1 mg/kg + GSPE 250 mg/kg (AFB₁ + GSPE). The results showed that GSPE significantly decreased serum inflammatory cytokines TNF-α, IFN-γ, IL-1β, IL-10, and IL-6 induced by AFB₁. Similarly, GSPE + AFB₁ treated group revealed a significant decrease in mRNA expressions of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β, and IL-6) in the splenic tissue compared to the AFB₁ treatment group. In addition, western blotting results manifested that GSPE treatment normalized the phosphorylation of nuclear factor kappa B (p65) and the degradation of IκBα protein induced by AFB₁. Furthermore, GSPE enhanced the antioxidant defense system through activating the nuclear factor-erythroid-2-related factor (Nrf2) signaling pathway. The mRNA and protein expression level of Nrf2 and its down streaming associated genes were noted up-regulated by the addition of GSPE, and down-regulated in the AFB₁ group. Taken together, GSPE alleviates AFB₁-induced immunotoxicity and oxidative damage by inhibiting the NF-κB and activating the Nrf2 signaling pathways in broiler chickens. Conclusively, our results suggest that GSPE could be considered as a potential natural agent for the prevention of AFB₁-induced immunotoxicity and oxidative damage. Full article

(This article belongs to the Special Issue Biological Control and Post-Harvest Detoxification of Mycotoxins as Strategies to Reduce the Impact of Mycotoxins)

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23 pages, 2325 KiB

Open AccessEditor’s ChoiceArticle

Interannual Variability of Dinophysis acuminata and Protoceratium reticulatum in a Chilean Fjord: Insights from the Realized Niche Analysis

by Catharina Alves-de-Souza, José Luis Iriarte and Jorge I. Mardones

Toxins 2019, 11(1), 19; https://doi.org/10.3390/toxins11010019 - 5 Jan 2019

Cited by 33 | Viewed by 5045

Abstract

Here, we present the interannual distribution of Dinophysis acuminata and Protoceratium reticulatum over a 10-year period in the Reloncaví Fjord, a highly stratified fjord in southern Chile. A realized subniche approach based on the Within Outlying Mean Index (WitOMI) was used to decompose [...] Read more.

Here, we present the interannual distribution of Dinophysis acuminata and Protoceratium reticulatum over a 10-year period in the Reloncaví Fjord, a highly stratified fjord in southern Chile. A realized subniche approach based on the Within Outlying Mean Index (WitOMI) was used to decompose the species’ realized niche into realized subniches (found within subsets of environmental conditions). The interannual distribution of both D. acuminata and P. reticulatum summer blooms was strongly influenced by climatological regional events, i.e., El Niño Southern Oscillation (ENSO) and the Southern Annual Mode (SAM). The two species showed distinct niche preferences, with blooms of D. acuminata occurring under La Niña conditions (cold years) and low river streamflow whereas P. reticulatum blooms were observed in years of El Niño conditions and positive SAM phase. The biological constraint exerted on the species was further estimated based on the difference between the existing fundamental subniche and the realized subniche. The observed patterns suggested that D. acuminata was subject to strong biological constraint during the studied period, probably as a result of low cell densities of its putative prey (the mixotrophic ciliate Mesodinium cf. rubrum) usually observed in the studied area. Full article

(This article belongs to the Special Issue Dinophysis Toxins: Distribution, Fate in Shellfish and Impacts)

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15 pages, 3785 KiB

Open AccessEditor’s ChoiceArticle

Lactobacillus bulgaricus or Lactobacillus rhamnosus Suppresses NF-κB Signaling Pathway and Protects against AFB₁-Induced Hepatitis: A Novel Potential Preventive Strategy for Aflatoxicosis?

by Yuanyuan Chen, Ruirui Li, Qiaocheng Chang, Zhihao Dong, Huanmin Yang and Chuang Xu

Toxins 2019, 11(1), 17; https://doi.org/10.3390/toxins11010017 - 4 Jan 2019

Cited by 39 | Viewed by 5075

Abstract

Aflatoxin B₁ (AFB₁), a mycotoxin found in food and feed, is immunotoxic to animals and poses significant threat to the food industry and animal production. The primary target of AFB₁ is the liver. To overcome aflatoxin toxicity, probiotic-mediated detoxification [...] Read more.

Aflatoxin B₁ (AFB₁), a mycotoxin found in food and feed, is immunotoxic to animals and poses significant threat to the food industry and animal production. The primary target of AFB₁ is the liver. To overcome aflatoxin toxicity, probiotic-mediated detoxification has been proposed. In the present study, to investigate the protective effects and molecular mechanisms of Lactobacillus bulgaricus or Lactobacillus rhamnosus against liver inflammatory responses to AFB₁, mice were administered with AFB₁ (300 μg/kg) and/or Lactobacillus intragastrically for 8 weeks. AML12 cells were cultured and treated with AFB₁, BAY 11-7082 (an NF-κB inhibitor), and different concentrations of L. bulgaricus or L. rhamnosus. The body weight, liver index, histopathological changes, biochemical indices, cytokines, cytotoxicity, and activation of the NF-κB signaling pathway were measured. AFB₁ exposure caused changes in liver histopathology and biochemical functions, altered inflammatory response, and activated the NF-κB pathway. Supplementation of L. bulgaricus or L. rhamnosus significantly prevented AFB₁-induced liver injury and alleviated histopathological changes and inflammatory response by decreasing NF-κB p65 expression. The results of in vitro experiments revealed that L. rhamnosus evidently protected against AFB₁-induced inflammatory response and decreased NF-κB p65 expression when compared with L. bulgaricus. These findings indicated that AFB₁ exposure can cause inflammatory response by inducing hepatic injury, and supplementation of L. bulgaricus or L. rhamnosus can produce significant protective effect against AFB₁-induced liver damage and inflammatory response by regulating the activation of the NF-κB signaling pathway. Full article

(This article belongs to the Collection Aflatoxins)

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14 pages, 13578 KiB

Open AccessEditor’s ChoiceArticle

Phytic Acid Decreases Oxidative Stress and Intestinal Lesions Induced by Fumonisin B₁ and Deoxynivalenol in Intestinal Explants of Pigs

by Elisângela O. Da Silva, Juliana R. Gerez, Miriam S. N. Hohmann, Waldiceu A. Verri, Jr. and Ana Paula F. R. L. Bracarense

Toxins 2019, 11(1), 18; https://doi.org/10.3390/toxins11010018 - 4 Jan 2019

Cited by 55 | Viewed by 4943

Abstract

The purpose of the present study was to investigate the effects of phytic acid (IP6) on morphological and immunohistochemical parameters and oxidative stress response in intestinal explants of pigs exposed to fumonisin B₁ (FB₁) and/or deoxynivalenol (DON). The jejunal explants [...] Read more.

The purpose of the present study was to investigate the effects of phytic acid (IP6) on morphological and immunohistochemical parameters and oxidative stress response in intestinal explants of pigs exposed to fumonisin B₁ (FB₁) and/or deoxynivalenol (DON). The jejunal explants were exposed to the following treatments: vehicle, IP6 5 mM, DON 10 µM, FB₁ 70 µM, DON 10 µM + FB₁ 70 µM, DON 10 µM + IP6 5 mM, FB₁ 70 µM + IP6 5 mM, and DON 10 µM + FB₁ 70 µM + IP6 5 mM. The decrease in villus height and goblet cell density was more evident in DON and DON + FB₁ treatments. In addition, a significant increase in cell apoptosis and cell proliferation and a decrease in E-cadherin expression were observed in the same groups. DON and FB₁ exposure increased cyclooxygenase-2 expression and decreased the cellular antioxidant capacity. An increase in lipid peroxidation was observed in DON- and FB₁-treated groups. IP6 showed beneficial effects, such as a reduction in intestinal morphological changes, cell apoptosis, cell proliferation, and cyclooxygenase-2 expression, and an increase in E-cadherin expression when compared with DON, FB₁ alone, or DON and FB₁ in association. IP6 inhibited oxidative stress and increased the antioxidant capacity in the explants exposed to mycotoxins. Full article

(This article belongs to the Section Mycotoxins)

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11 pages, 1133 KiB

Open AccessEditor’s ChoiceArticle

Toxic Indole Diterpenes from Endophyte-Infected Perennial Ryegrass Lolium perenne L.: Isolation and Stability

by Priyanka Reddy, Myrna A. Deseo, Vilnis Ezernieks, Kathryn Guthridge, German Spangenberg and Simone Rochfort

Toxins 2019, 11(1), 16; https://doi.org/10.3390/toxins11010016 - 3 Jan 2019

Cited by 15 | Viewed by 4822

Abstract

The most potent of the indole diterpenes, lolitrem B, is found in perennial ryegrass (Lolium perenne L.) infected with the endophyte Epichloë festucae var. lolii (also termed LpTG-1). Ingestion causes a neurological syndrome in grazing livestock called ryegrass staggers disease. To [...] Read more.

The most potent of the indole diterpenes, lolitrem B, is found in perennial ryegrass (Lolium perenne L.) infected with the endophyte Epichloë festucae var. lolii (also termed LpTG-1). Ingestion causes a neurological syndrome in grazing livestock called ryegrass staggers disease. To enable the rapid development of new forage varieties, the toxicity of lolitrem B and its biosynthetic intermediates needs to be established. However, most of these indole diterpenes are not commercially available; thus, isolation of these compounds is paramount. A concentrated endophyte-infected perennial ryegrass seed extract was subjected to silica flash chromatography followed by preparative HPLC and purification by crystallization resulting in lolitrem B and the intermediate compounds lolitrem E, paspaline and terpendole B. The four-step isolation and purification method resulted in a 25% yield of lolitrem B. After isolation, lolitrem B readily degraded to its biosynthetic intermediate, lolitriol. We also found that lolitrem B can readily degrade depending on the solvent and storage conditions. The facile method which takes into consideration the associated instability of lolitrem B, led to the purification of indole diterpenes in quantities sufficient for use as analytical standards for identification in pastures, and/or for toxicity testing in pasture development programs. Full article

(This article belongs to the Special Issue Fungal Infestations in Humans, Animals, Crops)

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12 pages, 9389 KiB

Open AccessEditor’s ChoiceArticle

In Vitro Cytotoxicity Induced by the Bufadienolides 1α,2α-Epoxyscillirosidine and Lanceotoxin B on Rat Myocardial and Mouse Neuroblastoma Cell Lines

by Danielle Henn, Annette Venter and Christo Botha

Toxins 2019, 11(1), 14; https://doi.org/10.3390/toxins11010014 - 2 Jan 2019

Cited by 7 | Viewed by 3136

Abstract

Consumption of bufadienolide-containing plants are responsible for many livestock mortalities annually. Bufadienolides are divided into two groups; non-cumulative bufadienolides and cumulative bufadienolides. Cumulative bufadienolides are referred to as neurotoxic, as the chronic intoxication with this type of bufadienolide results in a paretic/paralytic syndrome [...] Read more.

Consumption of bufadienolide-containing plants are responsible for many livestock mortalities annually. Bufadienolides are divided into two groups; non-cumulative bufadienolides and cumulative bufadienolides. Cumulative bufadienolides are referred to as neurotoxic, as the chronic intoxication with this type of bufadienolide results in a paretic/paralytic syndrome known as ‘krimpsiekte’. The in vitro cytotoxicity of a non-cumulative bufadienolide, 1α,2α-epoxyscillirosidine, and a cumulative bufadienolide, lanceotoxin B, were compared using the MTT ((3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction) assay after exposing rat myocardial (H9c2) and mouse neuroblastoma (Neuro-2a) cell lines. The effect of these two bufadienolides on cell ultrastructure was also investigated using transmission electron microscopy (TEM). H9c2 cells exhibited greater cytotoxicity when exposed to 1α,2α-epoxyscillirosidine, compared to lanceotoxin B. In contrast, Neuro-2a cells were more susceptible to lanceotoxin B. The EC₅₀ (half maximal effective concentration) of lanceotoxin B exposure of Neuro-2a cells for 24–72 h ranged from 4.4–5.5 µM compared to EC₅₀s of 35.7–37.6 µM for 1α,2α-epoxyscillirosidine exposure of Neuro-2a cells over the same period. 1α,2α-Epoxyscillirosidine induced extensive vacuolization in both cell types, with swollen RER (rough endoplasmic reticulum) and perinuclear spaces. Lanceotoxin B caused swelling of the mitochondria and sequestration of cytoplasmic material within autophagic vesicles. These results corroborate the notion that cumulative bufadienolides are neurotoxic. Full article

(This article belongs to the Collection Toxic and Pharmacological Effect of Plant Toxins)

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18 pages, 1522 KiB

Open AccessEditor’s ChoiceArticle

In Vitro and in Field Response of Different Fungicides against Aspergillus flavus and Fusarium Species Causing Ear Rot Disease of Maize

by Mario Masiello, Stefania Somma, Veronica Ghionna, Antonio Francesco Logrieco and Antonio Moretti

Toxins 2019, 11(1), 11; https://doi.org/10.3390/toxins11010011 - 1 Jan 2019

Cited by 67 | Viewed by 6987

Abstract

Aspergillus flavus, the main aflatoxin B₁ producing fungal species, Fusarium graminearum, a deoxynivalenol producer, and the fumonisin-producing species F. proliferatum and F. verticillioides are the main toxigenic fungi (TF) that colonize maize. Several strategies are available to control TF and [...] Read more.

Aspergillus flavus, the main aflatoxin B₁ producing fungal species, Fusarium graminearum, a deoxynivalenol producer, and the fumonisin-producing species F. proliferatum and F. verticillioides are the main toxigenic fungi (TF) that colonize maize. Several strategies are available to control TF and related mycotoxins, such as chemical control. However, there is poor knowledge on the efficacy of fungicides on maize plants since few molecules are registered. The sensitivity of F. graminearum, F. proliferatum, F. verticillioides, and A. flavus to eleven fungicides, selected based on their different modes of action, was evaluated in both in vitro assays and, after selection, in the field. In vitro, demethylation inhibitors (DMI) showed excellent performances, followed by thiophanate-methyl and folpet. Among the succinate dehydrogenase inhibitors (SDHI), isopyrazam showed a higher effectiveness against Fusarium species than boscalid, which was ineffective against Fusarium, like the phenyl-pyrrole fludioxonil. Furthermore, both SDHIs and fludioxonil were more active against A. flavus than Fusarium species. In field trials, prothioconazole and thiophanate-methyl were confirmed to be effective to reduce F. graminearum (52% and 48%) and F. proliferatum contamination (44% and 27%). On the other hand, prothioconazole and boscalid could reduce A. flavus contamination at values of 75% and 56%, respectively. Full article

(This article belongs to the Special Issue 2^nd MycoKey International Conference - Integrated Solutions for Mycotoxin Management)

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16 pages, 1903 KiB

Open AccessEditor’s ChoiceArticle

Comparative Analysis of Microcystin Prevalence in Michigan Lakes by Online Concentration LC/MS/MS and ELISA

by Johnna A. Birbeck, Judy A. Westrick, Grace M. O’Neill, Brian Spies and David C. Szlag

Toxins 2019, 11(1), 13; https://doi.org/10.3390/toxins11010013 - 1 Jan 2019

Cited by 57 | Viewed by 6478

Abstract

Fast and reliable workflows are needed to quantitate microcystins (MCs), a ubiquitous class of hepatotoxic cyanotoxins, so that the impact of human and environmental exposure is assessed quickly and minimized. Our goal was to develop a high-throughput online concentration liquid chromatography tandem mass [...] Read more.

Fast and reliable workflows are needed to quantitate microcystins (MCs), a ubiquitous class of hepatotoxic cyanotoxins, so that the impact of human and environmental exposure is assessed quickly and minimized. Our goal was to develop a high-throughput online concentration liquid chromatography tandem mass spectrometry (LC/MS/MS) workflow to quantitate the 12 commercially available MCs and nodularin in surface and drinking waters. The method run time was 8.5 min with detection limits in the low ng/L range and minimum reporting levels between 5 and 10 ng/L. This workflow was benchmarked by determining the prevalence of MCs and comparing the Adda-ELISA quantitation to our new workflow from 122 samples representing 31 waterbodies throughout Michigan. The frequency of MC occurrence was MC-LA > LR > RR > D-Asp³-LR > YR > HilR > WR > D-Asp³-RR > HtyR > LY = LW = LF, while MC-RR had the highest concentrations. MCs were detected in 33 samples and 13 of these samples had more than 20% of their total MC concentration from MCs not present in US Environmental Protection Agency (US EPA) Method 544. Furthermore, seasonal deviations between the LC/MS/MS and Adda-ELISA data suggest Adda-ELISA cross-reacts with MC degradation products. This workflow provides less than 24-h turnaround for quantification and also identified key differences between LC/MS/MS and ELISA quantitation that should be investigated further. Full article

(This article belongs to the Collection Freshwater HABs and Health in a Changing World)

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Review

22 pages, 2744 KiB

Open AccessEditor’s ChoiceReview

Shining a Light on Venom-Peptide Receptors: Venom Peptides as Targeted Agents for In Vivo Molecular Imaging

by Chun Yuen Chow and Glenn F. King

Toxins 2024, 16(7), 307; https://doi.org/10.3390/toxins16070307 - 4 Jul 2024

Cited by 1 | Viewed by 2399

Abstract

Molecular imaging has revolutionised the field of biomedical research by providing a non-invasive means to visualise and understand biochemical processes within living organisms. Optical fluorescent imaging in particular allows researchers to gain valuable insights into the dynamic behaviour of a target of interest [...] Read more.

Molecular imaging has revolutionised the field of biomedical research by providing a non-invasive means to visualise and understand biochemical processes within living organisms. Optical fluorescent imaging in particular allows researchers to gain valuable insights into the dynamic behaviour of a target of interest in real time. Ion channels play a fundamental role in cellular signalling, and they are implicated in diverse pathological conditions, making them an attractive target in the field of molecular imaging. Many venom peptides exhibit exquisite selectivity and potency towards ion channels, rendering them ideal agents for molecular imaging applications. In this review, we illustrate the use of fluorescently-labelled venom peptides for disease diagnostics and intraoperative imaging of brain tumours and peripheral nerves. Finally, we address challenges for the development and clinical translation of venom peptides as nerve-targeted imaging agents. Full article

(This article belongs to the Special Issue From Animal Venoms to Solutions: In Honor of Professor Lourival D. Possani on the Occasion of His 85th Birthday)

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36 pages, 4406 KiB

Open AccessEditor’s ChoiceReview

Update on Non-Interchangeability of Botulinum Neurotoxin Products

by Mitchell F. Brin, Mariana Nelson, Nazanin Ashourian, Amy Brideau-Andersen and John Maltman

Toxins 2024, 16(6), 266; https://doi.org/10.3390/toxins16060266 - 10 Jun 2024

Cited by 9 | Viewed by 4379

Abstract

The growing use of botulinum neurotoxins (BoNTs) for medical and aesthetic purposes has led to the development and marketing of an increasing number of BoNT products. Given that BoNTs are biological medications, their characteristics are heavily influenced by their manufacturing methods, leading to [...] Read more.

The growing use of botulinum neurotoxins (BoNTs) for medical and aesthetic purposes has led to the development and marketing of an increasing number of BoNT products. Given that BoNTs are biological medications, their characteristics are heavily influenced by their manufacturing methods, leading to unique products with distinct clinical characteristics. The manufacturing and formulation processes for each BoNT are proprietary, including the potency determination of reference standards and other features of the assays used to measure unit potency. As a result of these differences, units of BoNT products are not interchangeable or convertible using dose ratios. The intrinsic, product-level differences among BoNTs are compounded by differences in the injected tissues, which are innervated by different nerve fiber types (e.g., motor, sensory, and/or autonomic nerves) and require unique dosing and injection sites that are particularly evident when treating complex therapeutic and aesthetic conditions. It is also difficult to compare across studies due to inherent differences in patient populations and trial methods, necessitating attention to study details underlying each outcome reported. Ultimately, each BoNT possesses a unique clinical profile for which unit doses and injection paradigms must be determined individually for each indication. This practice will help minimize unexpected adverse events and maximize efficacy, duration, and patient satisfaction. With this approach, BoNT is poised to continue as a unique tool for achieving individual goals for an increasing number of medical and aesthetic indications. Full article

(This article belongs to the Section Bacterial Toxins)

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29 pages, 703 KiB

Open AccessEditor’s ChoiceReview

Embracing the Versatility of Botulinum Neurotoxins in Conventional and New Therapeutic Applications

by Christine Rasetti-Escargueil and Stefano Palea

Toxins 2024, 16(6), 261; https://doi.org/10.3390/toxins16060261 - 4 Jun 2024

Cited by 9 | Viewed by 6517

Abstract

Botulinum neurotoxins (BoNTs) have been used for almost half a century in the treatment of excessive muscle contractility. BoNTs are routinely used to treat movement disorders such as cervical dystonia, spastic conditions, blepharospasm, and hyperhidrosis, as well as for cosmetic purposes. In addition [...] Read more.

Botulinum neurotoxins (BoNTs) have been used for almost half a century in the treatment of excessive muscle contractility. BoNTs are routinely used to treat movement disorders such as cervical dystonia, spastic conditions, blepharospasm, and hyperhidrosis, as well as for cosmetic purposes. In addition to the conventional indications, the use of BoNTs to reduce pain has gained increased recognition, giving rise to an increasing number of indications in disorders associated with chronic pain. Furthermore, BoNT-derived formulations are benefiting a much wider range of patients suffering from overactive bladder, erectile dysfunction, arthropathy, neuropathic pain, and cancer. BoNTs are categorised into seven toxinotypes, two of which are in clinical use, and each toxinotype is divided into multiple subtypes. With the development of bioinformatic tools, new BoNT-like toxins have been identified in non-Clostridial organisms. In addition to the expanding indications of existing formulations, the rich variety of toxinotypes or subtypes in the wild-type BoNTs associated with new BoNT-like toxins expand the BoNT superfamily, forming the basis on which to develop new BoNT-based therapeutics as well as research tools. An overview of the diversity of the BoNT family along with their conventional therapeutic uses is presented in this review followed by the engineering and formulation opportunities opening avenues in therapy. Full article

(This article belongs to the Special Issue Clinical Applications and Diversity of Botulinum Toxins)

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24 pages, 7201 KiB

Open AccessEditor’s ChoiceReview

A Guide to the Clinical Management of Vipera Snakebite in Italy

by Matteo Riccardo Di Nicola, Marta Crevani, Ignazio Avella, Anna Cerullo, Jean-Lou C. M. Dorne, Giovanni Paolino and Caterina Zattera

Toxins 2024, 16(6), 255; https://doi.org/10.3390/toxins16060255 - 31 May 2024

Cited by 6 | Viewed by 3649

Abstract

The genus Vipera encompasses most species of medically significant venomous snakes of Europe, with Italy harbouring four of them. Envenomation by European vipers can result in severe consequences, but underreporting and the absence of standardised clinical protocols hinder effective snakebite management. This study [...] Read more.

The genus Vipera encompasses most species of medically significant venomous snakes of Europe, with Italy harbouring four of them. Envenomation by European vipers can result in severe consequences, but underreporting and the absence of standardised clinical protocols hinder effective snakebite management. This study provides an updated, detailed set of guidelines for the management and treatment of Vipera snakebite tailored for Italian clinicians. It includes taxonomic keys for snake identification, insights into viper venom composition, and recommendations for clinical management. Emphasis is placed on quick and reliable identification of medically relevant snake species, along with appropriate first aid measures. Criteria for antivenom administration are outlined, as well as indications on managing potential side effects. While the protocol is specific to Italy, its methodology can potentially be adapted for other European countries, depending on local resources. The promotion of comprehensive data collection and collaboration among Poison Control Centres is advocated to optimise envenomation management protocols and improve the reporting of epidemiological data concerning snakebite at the country level. Full article

(This article belongs to the Special Issue Venomous Snakes: Taxonomy, Toxicology and Clinical Management of Envenomation)

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18 pages, 633 KiB

Open AccessEditor’s ChoiceReview

Challenges of Diphtheria Toxin Detection

by Marta Prygiel, Ewa Mosiej, Maciej Polak, Katarzyna Krysztopa-Grzybowska, Karol Wdowiak, Kamila Formińska and Aleksandra A. Zasada

Toxins 2024, 16(6), 245; https://doi.org/10.3390/toxins16060245 - 26 May 2024

Viewed by 4177

Abstract

Diphtheria toxin (DT) is the main virulence factor of Corynebacterium diphtheriae, C. ulcerans and C. pseudotuberculosis. Moreover, new Corynebacterium species with the potential to produce diphtheria toxin have also been described. Therefore, the detection of the toxin is the most important test in [...] Read more.

Diphtheria toxin (DT) is the main virulence factor of Corynebacterium diphtheriae, C. ulcerans and C. pseudotuberculosis. Moreover, new Corynebacterium species with the potential to produce diphtheria toxin have also been described. Therefore, the detection of the toxin is the most important test in the microbiological diagnosis of diphtheria and other corynebacteria infections. Since the first demonstration in 1888 that DT is a major virulence factor of C. diphtheriae, responsible for the systemic manifestation of the disease, various methods for DT detection have been developed, but the diagnostic usefulness of most of them has not been confirmed on a sufficiently large group of samples. Despite substantial progress in the science and diagnostics of infectious diseases, the Elek test is still the basic recommended diagnostic test for DT detection. The challenge here is the poor availability of an antitoxin and declining experience even in reference laboratories due to the low prevalence of diphtheria in developed countries. However, recent and very promising assays have been developed with the potential for use as rapid point-of-care testing (POCT), such as ICS and LFIA for toxin detection, LAMP for tox gene detection, and biosensors for both. Full article

(This article belongs to the Special Issue Multi Methods for Detecting Natural Toxins)

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14 pages, 1000 KiB

Open AccessEditor’s ChoiceReview

A Historical Perspective on Uremia and Uremic Toxins

by Björn Meijers, Ward Zadora and Jerome Lowenstein

Toxins 2024, 16(5), 227; https://doi.org/10.3390/toxins16050227 - 15 May 2024

Cited by 5 | Viewed by 3323

Abstract

Uremia, also known as uremic syndrome, refers to the clinical symptoms in the final stage of renal failure. The definition of the term has changed over time due to an improved comprehension of the kidney’s function and the advancement of dialysis technology. Here, [...] Read more.

Uremia, also known as uremic syndrome, refers to the clinical symptoms in the final stage of renal failure. The definition of the term has changed over time due to an improved comprehension of the kidney’s function and the advancement of dialysis technology. Here, we aim to present an overview of the various concepts that have developed regarding uremia throughout the years. We provide a comprehensive review of the historical progression starting from the early days of Kolff and his predecessors, continuing with the initial research conducted by Niwa et al., and culminating in the remote sensing hypothesis of Nigam. Additionally, we explore the subsequent investigation into the function of these toxins as signaling molecules in various somatic cells. Full article

(This article belongs to the Special Issue Toxins: 15th Anniversary)

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18 pages, 1822 KiB

Open AccessEditor’s ChoiceReview

Microcystin Contamination in Irrigation Water and Health Risk

by Mohammed Haida, Fatima El Khalloufi, Richard Mugani, Yasser Essadki, Alexandre Campos, Vitor Vasconcelos and Brahim Oudra

Toxins 2024, 16(4), 196; https://doi.org/10.3390/toxins16040196 - 19 Apr 2024

Cited by 7 | Viewed by 3290

Abstract

Microcystins (MCs), natural hepatotoxic compounds produced by cyanobacteria, pose significant risks to water quality, ecosystem stability, and the well-being of animals, plants, and humans when present in elevated concentrations. The escalating contamination of irrigation water with MCs presents a growing threat to terrestrial [...] Read more.

Microcystins (MCs), natural hepatotoxic compounds produced by cyanobacteria, pose significant risks to water quality, ecosystem stability, and the well-being of animals, plants, and humans when present in elevated concentrations. The escalating contamination of irrigation water with MCs presents a growing threat to terrestrial plants. The customary practice of irrigating crops from local water sources, including lakes and ponds hosting cyanobacterial blooms, serves as a primary conduit for transferring these toxins. Due to their high chemical stability and low molecular weight, MCs have the potential to accumulate in various parts of plants, thereby increasing health hazards for consumers of agricultural products, which serve as the foundation of the Earth’s food chain. MCs can bioaccumulate, migrate, potentially biodegrade, and pose health hazards to humans within terrestrial food systems. This study highlights that MCs from irrigation water reservoirs can bioaccumulate and come into contact with plants, transferring into the food chain. Additionally, it investigates the natural mechanisms that organisms employ for conjugation and the microbial processes involved in MC degradation. To gain a comprehensive understanding of the role of MCs in the terrestrial food chain and to elucidate the specific health risks associated with consuming crops irrigated with water contaminated with these toxins, further research is necessary. Full article

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46 pages, 7856 KiB

Open AccessEditor’s ChoiceReview

Overview of Bacterial Protein Toxins from Pathogenic Bacteria: Mode of Action and Insights into Evolution

by Michel R. Popoff

Toxins 2024, 16(4), 182; https://doi.org/10.3390/toxins16040182 - 8 Apr 2024

Cited by 10 | Viewed by 8218

Abstract

Bacterial protein toxins are secreted by certain bacteria and are responsible for mild to severe diseases in humans and animals. They are among the most potent molecules known, which are active at very low concentrations. Bacterial protein toxins exhibit a wide diversity based [...] Read more.

Bacterial protein toxins are secreted by certain bacteria and are responsible for mild to severe diseases in humans and animals. They are among the most potent molecules known, which are active at very low concentrations. Bacterial protein toxins exhibit a wide diversity based on size, structure, and mode of action. Upon recognition of a cell surface receptor (protein, glycoprotein, and glycolipid), they are active either at the cell surface (signal transduction, membrane damage by pore formation, or hydrolysis of membrane compound(s)) or intracellularly. Various bacterial protein toxins have the ability to enter cells, most often using an endocytosis mechanism, and to deliver the effector domain into the cytosol, where it interacts with an intracellular target(s). According to the nature of the intracellular target(s) and type of modification, various cellular effects are induced (cell death, homeostasis modification, cytoskeleton alteration, blockade of exocytosis, etc.). The various modes of action of bacterial protein toxins are illustrated with representative examples. Insights in toxin evolution are discussed. Full article

(This article belongs to the Special Issue Toxins: 15th Anniversary)

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