Toxins

17 pages, 2135 KiB

Open AccessEditor’s ChoiceArticle

Molecular Phylogenetic Relationships, Trichothecene Chemotype Diversity and Aggressiveness of Strains in a Global Collection of Fusarium graminearum Species

by Chami Amarasinghe, Barbara Sharanowski and W.G. Dilantha Fernando

Toxins 2019, 11(5), 263; https://doi.org/10.3390/toxins11050263 - 11 May 2019

Cited by 30 | Viewed by 4481

Abstract

Fusarium head blight (FHB), caused principally by the species belonging to the Fusarium graminearum species complex (FGSC), is an important disease in wheat, barley, and other small grain crops worldwide. Grain infected with species in the FGSC may be contaminated with trichothecene mycotoxins [...] Read more.

Fusarium head blight (FHB), caused principally by the species belonging to the Fusarium graminearum species complex (FGSC), is an important disease in wheat, barley, and other small grain crops worldwide. Grain infected with species in the FGSC may be contaminated with trichothecene mycotoxins such as deoxynivalenol (DON) and nivalenol (NIV). In this study, we characterized the phylogenetic relationships, chemotype diversity, phenotypic characters, and aggressiveness of 150 strains in FGSC collected from eight different countries. Phylogenetic analysis based on portions of translation elongation factor 1-α (EF-1α) gene from 150 strains revealed six species in the FGSC, F. graminearum s.s, F. asiaticum, F. meridionale, F. cortaderiae, F. boothii, and F. austroamericanum. In this collection, 50% of the strains were 15-acetyldeoxynivalenol (15-ADON), 35% were 3-acetyldeoxynivalenol (3-ADON) and 15% were NIV. Evaluation of strains on moderately resistant (MR) wheat cultivar Carberry indicated that there is no significant difference among the species for FHB disease severity (DS), fusarium damaged kernel percentage (FDK%) and DON production. However, significant differences were observed among the chemotypes. Results showed significantly higher FHB DS, FDK%, DON production, growth rates, and macroconidia production for the 3-ADON strains than the 15-ADON and NIV strains. In addition, significant differences for FHB response variables were observed among the strains from different countries. Our results demonstrate that type and amount of trichothecene produced by a strain play a key role in determining the level of aggressiveness of that particular strain, regardless of the species. Full article

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

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21 pages, 5229 KiB

Open AccessEditor’s ChoiceArticle

Deoxynivalenol Modulates the Viability, ROS Production and Apoptosis in Prostate Cancer Cells

by Dominika Ewa Habrowska-Górczyńska, Karolina Kowalska, Kinga Anna Urbanek, Kamila Domińska, Agata Sakowicz and Agnieszka Wanda Piastowska-Ciesielska

Toxins 2019, 11(5), 265; https://doi.org/10.3390/toxins11050265 - 11 May 2019

Cited by 37 | Viewed by 5786

Abstract

Deoxynivalenol (DON), known as vomitoxin, a type B trichothecene, is produced by Fusarium. DON frequently contaminates cereal grains such as wheat, maize, oats, barley, rye, and rice. At the molecular level, it induces ribosomal stress, inflammation and apoptosis in eukaryotic cells. Our [...] Read more.

Deoxynivalenol (DON), known as vomitoxin, a type B trichothecene, is produced by Fusarium. DON frequently contaminates cereal grains such as wheat, maize, oats, barley, rye, and rice. At the molecular level, it induces ribosomal stress, inflammation and apoptosis in eukaryotic cells. Our findings indicate that DON modulates the viability of prostate cancer (PCa) cells and that the response to a single high dose of DON is dependent on the androgen-sensitivity of cells. DON appears to increase reactive oxygen species (ROS) production in cells, induces DNA damage, and triggers apoptosis. The effects of DON application in PCa cells are influenced by the mitogen-activated protein kinase (MAPK) and NFΚB- HIF-1α signaling pathways. Our results indicate that p53 is a crucial factor in DON-associated apoptosis in PCa cells. Taken together, our findings show that a single exposure to high concentrations of DON (2–5 µM) modulates the progression of PCa. Full article

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

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18 pages, 3799 KiB

Open AccessEditor’s ChoiceReview

Toxin–Antitoxin Systems in Bacillus subtilis

by Sabine Brantl and Peter Müller

Toxins 2019, 11(5), 262; https://doi.org/10.3390/toxins11050262 - 9 May 2019

Cited by 31 | Viewed by 7746

Abstract

Toxin–antitoxin (TA) systems were originally discovered as plasmid maintenance systems in a multitude of free-living bacteria, but were afterwards found to also be widespread in bacterial chromosomes. TA loci comprise two genes, one coding for a stable toxin whose overexpression kills the cell [...] Read more.

Toxin–antitoxin (TA) systems were originally discovered as plasmid maintenance systems in a multitude of free-living bacteria, but were afterwards found to also be widespread in bacterial chromosomes. TA loci comprise two genes, one coding for a stable toxin whose overexpression kills the cell or causes growth stasis, and the other coding for an unstable antitoxin that counteracts toxin action. Of the currently known six types of TA systems, in Bacillus subtilis, so far only type I and type II TA systems were found, all encoded on the chromosome. Here, we review our present knowledge of these systems, the mechanisms of antitoxin and toxin action, and the regulation of their expression, and we discuss their evolution and possible physiological role. Full article

(This article belongs to the Special Issue Toxin-antitoxin (TA) systems)

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17 pages, 2953 KiB

Open AccessEditor’s ChoiceArticle

NMR-Based Metabolic Profiles of Intact Zebrafish Embryos Exposed to Aflatoxin B1 Recapitulates Hepatotoxicity and Supports Possible Neurotoxicity

by Zain Zuberi, Muhamed N. H. Eeza, Joerg Matysik, John P. Berry and A. Alia

Toxins 2019, 11(5), 258; https://doi.org/10.3390/toxins11050258 - 8 May 2019

Cited by 42 | Viewed by 5652

Abstract

Aflatoxin B1 (AFB1) is a widespread contaminant of grains and other agricultural crops and is globally associated with both acute toxicity and carcinogenicity. In the present study, we utilized nuclear magnetic resonance (NMR), and specifically high-resolution magic angle spin (HRMAS) NMR, coupled to [...] Read more.

Aflatoxin B1 (AFB1) is a widespread contaminant of grains and other agricultural crops and is globally associated with both acute toxicity and carcinogenicity. In the present study, we utilized nuclear magnetic resonance (NMR), and specifically high-resolution magic angle spin (HRMAS) NMR, coupled to the zebrafish (Danio rerio) embryo toxicological model, to characterize metabolic profiles associated with exposure to AFB1. Exposure to AFB1 was associated with dose-dependent acute toxicity (i.e., lethality) and developmental deformities at micromolar (≤ 2 µM) concentrations. Toxicity of AFB1 was stage-dependent and specifically consistent, in this regard, with a role of the liver and phase I enzyme (i.e., cytochrome P450) bioactivation. Metabolic profiles of intact zebrafish embryos exposed to AFB1 were, furthermore, largely consistent with hepatotoxicity previously reported in mammalian systems including metabolites associated with cytotoxicity (i.e., loss of cellular membrane integrity), glutathione-based detoxification, and multiple pathways associated with the liver including amino acid, lipid, and carbohydrate (i.e., energy) metabolism. Taken together, these metabolic alterations enabled the proposal of an integrated model of the hepatotoxicity of AFB1 in the zebrafish embryo system. Interestingly, changes in amino acid neurotransmitters (i.e., Gly, Glu, and GABA), as a key modulator of neural development, supports a role in recently-reported neurobehavioral and neurodevelopmental effects of AFB1 in the zebrafish embryo model. The present study reinforces not only toxicological pathways of AFB1 (i.e., hepatotoxicity, neurotoxicity), but also multiple metabolites as potential biomarkers of exposure and toxicity. More generally, this underscores the capacity of NMR-based approaches, when coupled to animal models, as a powerful toxicometabolomics tool. Full article

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

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11 pages, 4020 KiB

Open AccessEditor’s ChoiceArticle

Comparison of Apoptosis and Autophagy in Human Chondrocytes Induced by the T-2 and HT-2 Toxins

by Fang-Fang Yu, Xia-Lu Lin, Xi Wang, Zhi-Guang Ping and Xiong Guo

Toxins 2019, 11(5), 260; https://doi.org/10.3390/toxins11050260 - 8 May 2019

Cited by 28 | Viewed by 4026

Abstract

In this report, we have investigated the apoptosis and autophagy of chondrocytes induced by the T-2 and HT-2 toxins. The viability of chondrocytes was measured by the MTT assay. Malondialdehyde (MDA) and superoxide dismutase (SOD) kits were used to measure the oxidative stress [...] Read more.

In this report, we have investigated the apoptosis and autophagy of chondrocytes induced by the T-2 and HT-2 toxins. The viability of chondrocytes was measured by the MTT assay. Malondialdehyde (MDA) and superoxide dismutase (SOD) kits were used to measure the oxidative stress of chondrocytes. The apoptosis of chondrocytes was measured using flow cytometry. Hoechst 33258 and MDC staining agents were introduced to analyze apoptosis and autophagy induction in chondrocytes, respectively. Protein expression of Bax, caspase-9, caspase-3, and Beclin1 was examined by western blotting analysis. The T-2 and HT-2 toxins significantly decreased the viability of chondrocytes in a time-dependent manner. The level of oxidative stress in chondrocytes induced by the T-2 toxin was significantly higher when compared with that of the HT-2 toxin. The apoptosis rate of chondrocytes induced by the T-2 toxin increased from 3.26 ± 1.03%, 18.38 ± 1.28%, 34.5 ± 1.40% to 49.67 ± 5.31%, whereas apoptosis rate of chondrocytes induced by the HT-2 toxin increased from 3.82 ± 1.03%, 11.61 ± 1.27%, 25.72 ± 2.95% to 36.28 ± 2.81% in 48 h incubation time. Hoechst 33258 staining confirmed that apoptosis of chondrocytes induced by the T-2 toxin was significantly higher than that observed when the chondrocytes were incubated with the HT-2 toxin. MDC staining revealed that the autophagy rate of chondrocytes induced by the T-2 toxin increased from 6.38% to 63.02%, whereas this rate induced by the HT-2 toxin changed from 6.08% to 53.33%. The expression levels of apoptosis and autophagy related proteins, Bax, caspase-9, caspase-3, and Beclin1 in chondrocytes induced by the T-2 toxin were significantly higher when compared with those levels induced by the HT-2 toxin. Full article

(This article belongs to the Special Issue Toxicological Effects of Mycotoxins on Target Cells)

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16 pages, 2506 KiB

Open AccessEditor’s ChoiceArticle

Recombinant Aflatoxin-Degrading F₄₂₀H₂-Dependent Reductase from Mycobacterium smegmatis Protects Mammalian Cells from Aflatoxin Toxicity

by Che-Hsing Li, Wei-Yang Li, I-Ning Hsu, Yung-Yu Liao, Chi-Ya Yang, Matthew C. Taylor, Yu-Fan Liu, Wei-Hao Huang, Hsiang-Hua Chang, Ho-Lo Huang, Shao-Chi Lo, Ting-Yu Lin, Wei-Che Sun, Ya-Yi Chuang, Yu-Chieh Yang, Ru-Huei Fu and Rong-Tzong Tsai

Toxins 2019, 11(5), 259; https://doi.org/10.3390/toxins11050259 - 8 May 2019

Cited by 28 | Viewed by 4580

Abstract

Aflatoxins are carcinogenic secondary metabolites of fungi that contaminate many staple crops and foods. Aflatoxin contamination is a worldwide problem, especially in developing countries, posing health hazards, e.g., causing aflatoxicosis and hepatocellular carcinoma, and even death. Biological solutions for aflatoxin detoxification are environmentally [...] Read more.

Aflatoxins are carcinogenic secondary metabolites of fungi that contaminate many staple crops and foods. Aflatoxin contamination is a worldwide problem, especially in developing countries, posing health hazards, e.g., causing aflatoxicosis and hepatocellular carcinoma, and even death. Biological solutions for aflatoxin detoxification are environmentally friendly and a cheaper alternative than chemical methods. The aims of the current study were to investigate: (1) the ability of MSMEG_5998, an aflatoxin-degrading F₄₂₀H₂-dependent reductase from Mycobacterium smegmatis, to degrade aflatoxin B1 (AFB1) and reduce AFB1-caused damage in HepG2 cell culture model; and (2) whether a thioredoxin (Trx) linkage of MSMEG_5998 enhanced the enzyme activity. We show that Trx-linked MSMEG_5998 degraded 63% AFB1 and native MSMEG_5998 degraded 31% after 4 h at 22 °C, indicating that the Trx-linked enzyme had a better AFB1-degrading ability. In a HepG2 cell culture model, Trx-linked MSMEG_5998 reduced DNA damage and p53-mediated apoptosis caused by AFB1 to a greater extent than the native enzyme. These findings suggest that Trx-linked MSMEG_5998 could potentially be developed to protect the liver from AFB1 damage, or as a candidate protein to reduce AFB1-related toxicity in animals. 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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13 pages, 4661 KiB

Open AccessEditor’s ChoiceArticle

Varanid Lizard Venoms Disrupt the Clotting Ability of Human Fibrinogen through Destructive Cleavage

by James S. Dobson, Christina N. Zdenek, Chris Hay, Aude Violette, Rudy Fourmy, Chip Cochran and Bryan G. Fry

Toxins 2019, 11(5), 255; https://doi.org/10.3390/toxins11050255 - 7 May 2019

Cited by 22 | Viewed by 9617

Abstract

The functional activities of Anguimorpha lizard venoms have received less attention compared to serpent lineages. Bite victims of varanid lizards often report persistent bleeding exceeding that expected for the mechanical damage of the bite. Research to date has identified the blockage of platelet [...] Read more.

The functional activities of Anguimorpha lizard venoms have received less attention compared to serpent lineages. Bite victims of varanid lizards often report persistent bleeding exceeding that expected for the mechanical damage of the bite. Research to date has identified the blockage of platelet aggregation as one bleeding-inducing activity, and destructive cleavage of fibrinogen as another. However, the ability of the venoms to prevent clot formation has not been directly investigated. Using a thromboelastograph (TEG5000), clot strength was measured after incubating human fibrinogen with Heloderma and Varanus lizard venoms. Clot strengths were found to be highly variable, with the most potent effects produced by incubation with Varanus venoms from the Odatria and Euprepriosaurus clades. The most fibrinogenolytically active venoms belonged to arboreal species and therefore prey escape potential is likely a strong evolutionary selection pressure. The results are also consistent with reports of profusive bleeding from bites from other notably fibrinogenolytic species, such as V. giganteus. Our results provide evidence in favour of the predatory role of venom in varanid lizards, thus shedding light on the evolution of venom in reptiles and revealing potential new sources of bioactive molecules useful as lead compounds in drug design and development. Full article

(This article belongs to the Special Issue Assessment of Animal Toxin Function with Novel Viscoelastic Methods)

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11 pages, 1018 KiB

Open AccessEditor’s ChoiceArticle

Fusarium Mycotoxins Stability during the Malting and Brewing Processes

by Karim C. Piacentini, Sylvie Běláková, Karolína Benešová, Marek Pernica, Geovana D. Savi, Liliana O. Rocha, Ivo Hartman, Josef Čáslavský and Benedito Corrêa

Toxins 2019, 11(5), 257; https://doi.org/10.3390/toxins11050257 - 7 May 2019

Cited by 29 | Viewed by 4697

Abstract

Mycotoxins are widely studied by many research groups in all aspects, but the stability of these compounds needs further research for clarification. The objective of this study is to evaluate deoxynivalenol and zearalenone stability during all steps of the malting and brewing processes. [...] Read more.

Mycotoxins are widely studied by many research groups in all aspects, but the stability of these compounds needs further research for clarification. The objective of this study is to evaluate deoxynivalenol and zearalenone stability during all steps of the malting and brewing processes. The levels of these compounds decreased significantly during the production process (barley to beer). During the malting process, the DON levels decreased significantly in the steeping, germination, and malting steps (62%, 51.5%, and 68%, respectively). Considering ZEN, when the levels were compared between barley and the last step of the process, a significant decrease was observed. Most of the mycotoxins produced were transferred to the rootlets and spent grains, which is advantageous considering the final product. Furthermore, the mycotoxin dietary intake estimation was included in this study. The results proved that if the concentrations of target mycotoxins in raw material are under the limits established by the regulations, the levels decrease during the malting and brewing processes and make the beer secure for consumers. The quality of the five commodities involved in the beer process plays a decisive role in the creation of a safe final product. Full article

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

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16 pages, 1924 KiB

Open AccessEditor’s ChoiceReview

Type I Toxin-Antitoxin Systems in Clostridia

by Olga Soutourina

Toxins 2019, 11(5), 253; https://doi.org/10.3390/toxins11050253 - 6 May 2019

Cited by 19 | Viewed by 4639

Abstract

Type I toxin-antitoxin (TA) modules are abundant in both bacterial plasmids and chromosomes and usually encode a small hydrophobic toxic protein and an antisense RNA acting as an antitoxin. The RNA antitoxin neutralizes toxin mRNA by inhibiting its translation and/or promoting its degradation. [...] Read more.

Type I toxin-antitoxin (TA) modules are abundant in both bacterial plasmids and chromosomes and usually encode a small hydrophobic toxic protein and an antisense RNA acting as an antitoxin. The RNA antitoxin neutralizes toxin mRNA by inhibiting its translation and/or promoting its degradation. This review summarizes our current knowledge of the type I TA modules identified in Clostridia species focusing on the recent findings in the human pathogen Clostridium difficile. More than ten functional type I TA modules have been identified in the genome of this emerging enteropathogen that could potentially contribute to its fitness and success inside the host. Despite the absence of sequence homology, the comparison of these newly identified type I TA modules with previously studied systems in other Gram-positive bacteria, i.e., Bacillus subtilis and Staphylococcus aureus, revealed some important common traits. These include the conservation of characteristic sequence features for small hydrophobic toxic proteins, the localization of several type I TA within prophage or prophage-like regions and strong connections with stress response. Potential functions in the stabilization of genome regions, adaptations to stress conditions and interactions with CRISPR-Cas defence system, as well as promising applications of TA for genome-editing and antimicrobial developments are discussed. Full article

(This article belongs to the Special Issue Toxin-antitoxin (TA) systems)

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15 pages, 656 KiB

Open AccessEditor’s ChoiceArticle

Analysis of Toxigenic Fusarium Species Associated with Wheat Grain from Three Regions of Russia: Volga, Ural, and West Siberia

by Tatiana Gagkaeva, Olga Gavrilova, Aleksandra Orina, Yuri Lebedin, Ilya Shanin, Pavel Petukhov and Sergei Eremin

Toxins 2019, 11(5), 252; https://doi.org/10.3390/toxins11050252 - 5 May 2019

Cited by 31 | Viewed by 4087

Abstract

Wheat grains collected in three regions of Russia—Volga, Ural, and West Siberia—were analyzed for triangulation of methods in analysis of toxigenic Fusarium species. The presence of fungi and quantitative content of their biomass were detected by using various analytical methods, including a mycological [...] Read more.

Wheat grains collected in three regions of Russia—Volga, Ural, and West Siberia—were analyzed for triangulation of methods in analysis of toxigenic Fusarium species. The presence of fungi and quantitative content of their biomass were detected by using various analytical methods, including a mycological and immunochemical methods, and quantitative PCR. Additionally, an enzyme-linked immunosorbent assay and high-performance liquid chromatography with tandem mass spectrometry were applied for determination of mycotoxins. Regional differences were found regarding the contamination of wheat grain by Fusarium fungi and their toxins. The most important observation was the detection of F. graminearum in the Ural and West Siberian regions, where this pathogen had not been found previously. A maximum damaged grains by F. graminearum and F. sporotrichioides was found in the grain samples from West Siberia. The DNA of F. graminearum was detected in 19.2% and DNA of F. sporotrichioides was found in 84.1% of the analyzed grain samples. The amount of Fusarium antigens in the grain samples from the West Siberian region was 7–8 times higher than in the grain samples from the other two regions. Significant contamination of the grain with deoxynivalenol and T-2/HT-2 toxins (maximum contents were 2239 ppb and 199 ppb, respectively) was detected in the West Siberian region. Full article

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

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11 pages, 1107 KiB

Open AccessEditor’s ChoiceArticle

Toxicity Studies of Chanoclavine in Mice

by Sarah C. Finch, John S. Munday, Jan M. Sprosen and Sweta Bhattarai

Toxins 2019, 11(5), 249; https://doi.org/10.3390/toxins11050249 - 2 May 2019

Cited by 13 | Viewed by 6252

Abstract

Epichloë endophytes have been used successfully in pastoral grasses providing protection against insect pests through the expression of secondary metabolites. This approach could be extended to other plant species, such as cereals, reducing reliance on pesticides. To be successful, the selected endophyte must [...] Read more.

Epichloë endophytes have been used successfully in pastoral grasses providing protection against insect pests through the expression of secondary metabolites. This approach could be extended to other plant species, such as cereals, reducing reliance on pesticides. To be successful, the selected endophyte must express secondary metabolites that are active against cereal insect pests without any secondary metabolite, which is harmful to animals. Chanoclavine is of interest as it is commonly expressed by endophytes and has potential insecticidal activity. Investigation of possible mammalian toxicity is therefore required. An acute oral toxicity study showed the median lethal dose of chanoclavine to be >2000 mg/kg. This allows it to be classified as category 5 using the globally harmonized system of classification and labelling of chemicals, and category 6.1E using the New Zealand Hazardous Substances and New Organisms (HSNO) hazard classes, the lowest hazard class under both systems of classification. A three-week feeding study was also performed, which showed chanoclavine, at a dose rate of 123.9 mg/kg/day, initially reduced food consumption but was resolved by day seven. No toxicologically significant effects on gross pathology, histology, hematology, or blood chemistry were observed. These experiments showed chanoclavine to be of low toxicity and raised no food safety concerns. Full article

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

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21 pages, 3309 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Dissecting Toxicity: The Venom Gland Transcriptome and the Venom Proteome of the Highly Venomous Scorpion Centruroides limpidus (Karsch, 1879)

by Jimena I. Cid-Uribe, Erika P. Meneses, Cesar V. F. Batista, Ernesto Ortiz and Lourival D. Possani

Toxins 2019, 11(5), 247; https://doi.org/10.3390/toxins11050247 - 30 Apr 2019

Cited by 30 | Viewed by 6825

Abstract

Venom glands and soluble venom from the Mexican scorpion Centruroides limpidus (Karsch, 1879) were used for transcriptomic and proteomic analyses, respectively. An RNA-seq was performed by high-throughput sequencing with the Illumina platform. Approximately 80 million reads were obtained and assembled into 198,662 putative [...] Read more.

Venom glands and soluble venom from the Mexican scorpion Centruroides limpidus (Karsch, 1879) were used for transcriptomic and proteomic analyses, respectively. An RNA-seq was performed by high-throughput sequencing with the Illumina platform. Approximately 80 million reads were obtained and assembled into 198,662 putative transcripts, of which 11,058 were annotated by similarity to sequences from available databases. A total of 192 venom-related sequences were identified, including Na⁺ and K⁺ channel-acting toxins, enzymes, host defense peptides, and other venom components. The most diverse transcripts were those potentially coding for ion channel-acting toxins, mainly those active on Na⁺ channels (NaScTx). Sequences corresponding to β- scorpion toxins active of K⁺ channels (KScTx) and λ-KScTx are here reported for the first time for a scorpion of the genus Centruroides. Mass fingerprint corroborated that NaScTx are the most abundant components in this venom. Liquid chromatography coupled to mass spectometry (LC-MS/MS) allowed the identification of 46 peptides matching sequences encoded in the transcriptome, confirming their expression in the venom. This study corroborates that, in the venom of toxic buthid scorpions, the more abundant and diverse components are ion channel-acting toxins, mainly NaScTx, while they lack the HDP diversity previously demonstrated for the non-buthid scorpions. The highly abundant and diverse antareases explain the pancreatitis observed after envenomation by this species. Full article

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

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34 pages, 384 KiB

Open AccessEditor’s ChoiceReview

Fusarium Toxins in Chinese Wheat since the 1980s

by Jianbo Qiu, Jianhong Xu and Jianrong Shi

Toxins 2019, 11(5), 248; https://doi.org/10.3390/toxins11050248 - 30 Apr 2019

Cited by 53 | Viewed by 4394

Abstract

Wheat Fusarium head blight (FHB), caused by Fusarium species, is a widespread and destructive fungal disease. In addition to the substantial yield and revenue losses, diseased grains are often contaminated with Fusarium mycotoxins, making them unsuitable for human consumption or use as animal [...] Read more.

Wheat Fusarium head blight (FHB), caused by Fusarium species, is a widespread and destructive fungal disease. In addition to the substantial yield and revenue losses, diseased grains are often contaminated with Fusarium mycotoxins, making them unsuitable for human consumption or use as animal feed. As a vital food and feed ingredient in China, the quality and safety of wheat and its products have gained growing attention from consumers, producers, scientists, and policymakers. This review supplies detailed data about the occurrence of Fusarium toxins and related intoxications from the 1980s to the present. Despite the serious situation of toxin contamination in wheat, the concentration of toxins in flour is usually lower than that in raw materials, and food-poisoning incidents have been considerably reduced. Much work has been conducted on every phase of toxin production and wheat circulation by scientific researchers. Regulations for maximum contamination limits have been established in recent years and play a substantial role in ensuring the stability of the national economy and people’s livelihoods. Full article

(This article belongs to the Special Issue Fungal Growth and Mycotoxins: Challenges for developing countries)

21 pages, 924 KiB

Open AccessEditor’s ChoiceReview

The Mechanisms of Social Immunity Against Fungal Infections in Eusocial Insects

by Long Liu, Xing-Ying Zhao, Qing-Bo Tang, Chao-Liang Lei and Qiu-Ying Huang

Toxins 2019, 11(5), 244; https://doi.org/10.3390/toxins11050244 - 29 Apr 2019

Cited by 78 | Viewed by 8252

Abstract

Entomopathogenic fungus as well as their toxins is a natural threat surrounding social insect colonies. To defend against them, social insects have evolved a series of unique disease defenses at the colony level, which consists of behavioral and physiological adaptations. These colony-level defenses [...] Read more.

Entomopathogenic fungus as well as their toxins is a natural threat surrounding social insect colonies. To defend against them, social insects have evolved a series of unique disease defenses at the colony level, which consists of behavioral and physiological adaptations. These colony-level defenses can reduce the infection and poisoning risk and improve the survival of societal members, and is known as social immunity. In this review, we discuss how social immunity enables the insect colony to avoid, resist and tolerate fungal pathogens. To understand the molecular basis of social immunity, we highlight several genetic elements and biochemical factors that drive the colony-level defense, which needs further verification. We discuss the chemosensory genes in regulating social behaviors, the antifungal secretions such as some insect venoms in external defense and the immune priming in internal defense. To conclude, we show the possible driving force of the fungal toxins for the evolution of social immunity. Throughout the review, we propose several questions involved in social immunity extended from some phenomena that have been reported. We hope our review about social ‘host–fungal pathogen’ interactions will help us further understand the mechanism of social immunity in eusocial insects. Full article

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

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16 pages, 1759 KiB

Open AccessEditor’s ChoiceReview

How Ricin Damages the Ribosome

by Przemysław Grela, Monika Szajwaj, Patrycja Horbowicz-Drożdżal and Marek Tchórzewski

Toxins 2019, 11(5), 241; https://doi.org/10.3390/toxins11050241 - 27 Apr 2019

Cited by 49 | Viewed by 8025

Abstract

Ricin belongs to the group of ribosome-inactivating proteins (RIPs), i.e., toxins that have evolved to provide particular species with an advantage over other competitors in nature. Ricin possesses RNA N-glycosidase activity enabling the toxin to eliminate a single adenine base from the sarcin-ricin [...] Read more.

Ricin belongs to the group of ribosome-inactivating proteins (RIPs), i.e., toxins that have evolved to provide particular species with an advantage over other competitors in nature. Ricin possesses RNA N-glycosidase activity enabling the toxin to eliminate a single adenine base from the sarcin-ricin RNA loop (SRL), which is a highly conserved structure present on the large ribosomal subunit in all species from the three domains of life. The SRL belongs to the GTPase associated center (GAC), i.e., a ribosomal element involved in conferring unidirectional trajectory for the translational apparatus at the expense of GTP hydrolysis by translational GTPases (trGTPases). The SRL represents a critical element in the GAC, being the main triggering factor of GTP hydrolysis by trGTPases. Enzymatic removal of a single adenine base at the tip of SRL by ricin blocks GTP hydrolysis and, at the same time, impedes functioning of the translational machinery. Here, we discuss the consequences of SRL depurination by ricin for ribosomal performance, with emphasis on the mechanistic model overview of the SRL modus operandi. Full article

(This article belongs to the Special Issue Ricin Toxins)

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25 pages, 388 KiB

Open AccessEditor’s ChoiceReview

Public Health Risks Associated with Tetrodotoxin and Its Analogues in European Waters: Recent Advances after The EFSA Scientific Opinion

by Panagiota Katikou

Toxins 2019, 11(5), 240; https://doi.org/10.3390/toxins11050240 - 26 Apr 2019

Cited by 40 | Viewed by 6210

Abstract

Tetrodotoxin (TTX) and its analogues are naturally occurring toxins responsible worldwide for human intoxication cases and fatalities, mainly associated with pufferfish consumption. In the last decade, TTXs were detected in marine bivalves and gastropods from European waters. As TTXs are not regulated or [...] Read more.

Tetrodotoxin (TTX) and its analogues are naturally occurring toxins responsible worldwide for human intoxication cases and fatalities, mainly associated with pufferfish consumption. In the last decade, TTXs were detected in marine bivalves and gastropods from European waters. As TTXs are not regulated or monitored at EU level, their unexpected occurrence in shellfish raised concerns as a food safety hazard and revealed the necessity of a thorough assessment on the public health risks associated with their presence. For this reason, the European Food Safety Authority (EFSA) was requested by the European Commission to provide a scientific opinion, finally adopted in March 2017, according to which a provisional concentration below 44 μg TTX equivalents/kg shellfish meat, based on a large portion size of 400 g, was considered not to result in adverse effects in humans. The EFSA expert panel, however, recognized a number of shortcomings and uncertainties related to the unavailability of sufficient scientific data and provided relevant recommendations for future research to overcome these data gaps identified in order to further refine the risk assessment on TTXs. The present review aims to summarize the knowledge obtained towards addressing these recommendations in the two years following publication of the EFSA opinion, at the same time highlighting the points requiring further investigation. Full article

(This article belongs to the Special Issue Tetrodotoxins)

15 pages, 828 KiB

Open AccessEditor’s ChoiceArticle

Uremic Toxin Concentrations are Related to Residual Kidney Function in the Pediatric Hemodialysis Population

by Evelien Snauwaert, Els Holvoet, Wim Van Biesen, Ann Raes, Griet Glorieux, Johan Vande Walle, Sanne Roels, Raymond Vanholder, Varvara Askiti, Karolis Azukaitis, Aysun Bayazit, Nur Canpolat, Michel Fischbach, Nathalie Godefroid, Saoussen Krid, Mieczyslaw Litwin, Lukasz Obrycki, Fabio Paglialonga, Bruno Ranchin, Charlotte Samaille, Franz Schaefer, Claus Peter Schmitt, Brankica Spasojevic, Constantinos J. Stefanidis, Maria Van Dyck, Koen Van Hoeck, Laure Collard, Sunny Eloot and Rukshana Shroff Show full author list Hide full author list

Toxins 2019, 11(4), 235; https://doi.org/10.3390/toxins11040235 - 24 Apr 2019

Cited by 24 | Viewed by 4426

Abstract

Protein-bound uremic toxins (PBUTs) play a role in the multisystem disease that children on hemodialysis (HD) are facing, but little is known about their levels and protein binding (%PB). In this study, we evaluated the levels and %PB of six PBUTs cross-sectionally in [...] Read more.

Protein-bound uremic toxins (PBUTs) play a role in the multisystem disease that children on hemodialysis (HD) are facing, but little is known about their levels and protein binding (%PB). In this study, we evaluated the levels and %PB of six PBUTs cross-sectionally in a large pediatric HD cohort (n = 170) by comparing these with healthy and non-dialysis chronic kidney disease (CKD) stage 4–5 (n = 24) children. In parallel β2-microglobulin (β2M) and uric acid (UA) were evaluated. We then explored the impact of age and residual kidney function on uremic toxin levels and %PB using analysis of covariance and Spearman correlation coefficients (r_s). We found higher levels of β2M, p-cresyl glucuronide (pCG), hippuric acid (HA), indole acetic acid (IAA), and indoxyl sulfate (IxS) in the HD compared to the CKD4–5 group. In the HD group, a positive correlation between age and pCG, HA, IxS, and pCS levels was shown. Residual urine volume was negatively correlated with levels of β2M, pCG, HA, IAA, IxS, and CMPF (r_s −0.2 to −0.5). In addition, we found overall lower %PB of PBUTs in HD versus the CKD4–5 group, and showed an age-dependent increase in %PB of IAA, IxS, and pCS. Furhtermore, residual kidney function was overall positively correlated with %PB of PBUTs. In conclusion, residual kidney function and age contribute to PBUT levels and %PB in the pediatric HD population. Full article

(This article belongs to the Special Issue Disposition of Uremic Toxins: The Challenges in Uremia)

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15 pages, 5100 KiB

Open AccessEditor’s ChoiceArticle

Structural Insights to the Heterotetrameric Interaction between the Vibrio parahaemolyticus PirA^vp and PirB^vp Toxins and Activation of the Cry-Like Pore-Forming Domain

by Shin-Jen Lin, Yi-Fan Chen, Kai-Cheng Hsu, Yun-Ling Chen, Tzu-Ping Ko, Chu-Fang Lo, Han-Ching Wang and Hao-Ching Wang

Toxins 2019, 11(4), 233; https://doi.org/10.3390/toxins11040233 - 22 Apr 2019

Cited by 32 | Viewed by 6072

Abstract

Acute hepatopancreatic necrosis disease (AHPND) is a newly emergent penaeid shrimp disease which can cause 70–100% mortality in Penaeus vannamei and Penaeus monodon, and has resulted in enormous economic losses since its appearance. AHPND is caused by the specific strains of Vibrio [...] Read more.

Acute hepatopancreatic necrosis disease (AHPND) is a newly emergent penaeid shrimp disease which can cause 70–100% mortality in Penaeus vannamei and Penaeus monodon, and has resulted in enormous economic losses since its appearance. AHPND is caused by the specific strains of Vibrio parahaemolyticus that harbor the pVA1 plasmid and express PirA^vp and PirB^vp toxins. These two toxins have been reported to form a binary complex. When both are present, they lead to the death of shrimp epithelial cells in the hepatopancreas and cause the typical histological symptoms of AHPND. However, the binding mode of PirA^vp and PirB^vp has not yet been determined. Here, we used isothermal titration calorimetry (ITC) to measure the binding affinity of PirA^vp and PirB^vp. Since the dissociation constant (K_d = 7.33 ± 1.20 μM) was considered too low to form a sufficiently stable complex for X-ray crystallographic analysis, we used alternative methods to investigate PirA^vp-PirB^vp interaction, first by using gel filtration to evaluate the molecular weight of the PirA^vp/PirB^vp complex, and then by using cross-linking and hydrogen-deuterium exchange (HDX) mass spectrometry to further understand the interaction interface between PirA^vp and PirB^vp. Based on these results, we propose a heterotetrameric interaction model of this binary toxin complex. This model provides insight of how conformational changes might activate the PirB^vp N-terminal pore-forming domain and should be helpful for devising effective anti-AHPND strategies in the future. Full article

(This article belongs to the Special Issue Pore-Forming Toxins (PFTs): Never Out of Fashion)

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9 pages, 741 KiB

Open AccessEditor’s ChoiceArticle

Antiparasitic Properties of Cantharidin and the Blister Beetle Berberomeloe majalis (Coleoptera: Meloidae)

by Douglas W. Whitman, Maria Fe Andrés, Rafael A. Martínez-Díaz, Alexandra Ibáñez-Escribano, A. Sonia Olmeda and Azucena González-Coloma

Toxins 2019, 11(4), 234; https://doi.org/10.3390/toxins11040234 - 22 Apr 2019

Cited by 23 | Viewed by 8886

Abstract

Cantharidin (CTD) is a toxic monoterpene produced by blister beetles (Fam. Meloidae) as a chemical defense against predators. Although CTD is highly poisonous to many predator species, some have evolved the ability to feed on poisonous Meloidae, or otherwise beneficially use blister beetles. [...] Read more.

Cantharidin (CTD) is a toxic monoterpene produced by blister beetles (Fam. Meloidae) as a chemical defense against predators. Although CTD is highly poisonous to many predator species, some have evolved the ability to feed on poisonous Meloidae, or otherwise beneficially use blister beetles. Great Bustards, Otis tarda, eat CTD-containing Berberomeloe majalis blister beetles, and it has been hypothesized that beetle consumption by these birds reduces parasite load (a case of self-medication). We examined this hypothesis by testing diverse organisms against CTD and extracts of B. majalis hemolymph and bodies. Our results show that all three preparations (CTD and extracts of B. majalis) were toxic to a protozoan (Trichomonas vaginalis), a nematode (Meloidogyne javanica), two insects (Myzus persicae and Rhopalosiphum padi) and a tick (Hyalomma lusitanicum). This not only supports the anti-parasitic hypothesis for beetle consumption, but suggests potential new roles for CTD, under certain conditions. Full article

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

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18 pages, 2545 KiB

Open AccessEditor’s ChoiceArticle

A Complete Survey of Glycoalkaloids Using LC-FTICR-MS and IRMPD in a Commercial Variety and a Local Landrace of Eggplant (Solanum melongena L.) and their Anticholinesterase and Antioxidant Activities

by Filomena Lelario, Susanna De Maria, Anna Rita Rivelli, Daniela Russo, Luigi Milella, Sabino Aurelio Bufo and Laura Scrano

Toxins 2019, 11(4), 230; https://doi.org/10.3390/toxins11040230 - 19 Apr 2019

Cited by 38 | Viewed by 7083

Abstract

Eggplant contains glycoalkaloids (GAs), a class of nitrogen-containing secondary metabolites of great structural variety that may have both adverse and beneficial biological effects. In this study, we performed a complete survey of GAs and their malonylated form, in two genotypes of eggplants: A [...] Read more.

Eggplant contains glycoalkaloids (GAs), a class of nitrogen-containing secondary metabolites of great structural variety that may have both adverse and beneficial biological effects. In this study, we performed a complete survey of GAs and their malonylated form, in two genotypes of eggplants: A commercial cultivated type, Mirabella (Mir), with purple peel and bitter taste and a local landrace, named Melanzana Bianca di Senise (Sen), characterized by white peel with purple strip and a typical sweet aroma. Besides the analysis of their morphological traits, nineteen glycoalkaloids were tentatively identified in eggplant berry extracts based upon LC-ESI-FTICR-MS analysis using retention times, elution orders, high-resolution mass spectra, as well as high-resolution fragmentation by IRMPD. The relative signal intensities (i.e., ion counts) of the GAs identified in Mir and Sen pulp extracts showed as solamargine, and its isomers are the most abundant. In addition, anticholinesterase and antioxidant activities of the extracts were evaluated. Pulp tissue was found to be more active in inhibiting acetylcholinesterase enzyme than peel showing an inhibitory effect higher than 20% for Mir pulp. The identification of new malonylated GAs in eggplant is proposed. Full article

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

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14 pages, 2686 KiB

Open AccessEditor’s ChoiceArticle

Dehydrocrenatidine Inhibits Voltage-Gated Sodium Channels and Ameliorates Mechanic Allodia in a Rat Model of Neuropathic Pain

by Fang Zhao, Qinglian Tang, Jian Xu, Shuangyan Wang, Shaoheng Li, Xiaohan Zou and Zhengyu Cao

Toxins 2019, 11(4), 229; https://doi.org/10.3390/toxins11040229 - 18 Apr 2019

Cited by 16 | Viewed by 4367

Abstract

Picrasma quassioides (D. Don) Benn, a medical plant, is used in clinic to treat inflammation, pain, sore throat, and eczema. The alkaloids are the main active components in P. quassioides. In this study, we examined the analgesic effect of dehydrocrenatidine (DHCT), a [...] Read more.

Picrasma quassioides (D. Don) Benn, a medical plant, is used in clinic to treat inflammation, pain, sore throat, and eczema. The alkaloids are the main active components in P. quassioides. In this study, we examined the analgesic effect of dehydrocrenatidine (DHCT), a β-carboline alkaloid abundantly found in P. quassioides in a neuropathic pain rat model of a sciatic nerve chronic constriction injury. DHCT dose-dependently attenuated the mechanic allodynia. In acutely isolated dorsal root ganglion, DHCT completely suppressed the action potential firing. Further electrophysiological characterization demonstrated that DHCT suppressed both tetrodotoxin-resistant (TTX-R) and sensitive (TTX-S) voltage-gated sodium channel (VGSC) currents with IC₅₀ values of 12.36 μM and 4.87 µM, respectively. DHCT shifted half-maximal voltage (V_1/2) of inactivation to hyperpolarizing direction by ~16.7 mV in TTX-S VGSCs. In TTX-R VGSCs, DHCT shifted V_1/2 of inactivation voltage to hyperpolarizing direction and V_1/2 of activation voltage to more depolarizing potential by ~23.9 mV and ~12.2 mV, respectively. DHCT preferred to interact with an inactivated state of VGSCs and prolonged the repriming time in both TTX-S and TTX-R VGSCs, transiting the channels into a slow inactivated state from a fast inactivated state. Considered together, these data demonstrated that the analgesic effect of DHCT was likely though the inhibition of neuronal excitability. Full article

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

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12 pages, 2837 KiB

Open AccessEditor’s ChoiceArticle

l-Proline Alleviates Kidney Injury Caused by AFB1 and AFM1 through Regulating Excessive Apoptosis of Kidney Cells

by Huiying Li, Songli Li, Huaigu Yang, Yizhen Wang, Jiaqi Wang and Nan Zheng

Toxins 2019, 11(4), 226; https://doi.org/10.3390/toxins11040226 - 16 Apr 2019

Cited by 46 | Viewed by 4950

Abstract

The toxicity and related mechanisms of aflatoxin B1 (AFB1) and aflatoxin M1 (AFM1) in the mouse kidney were studied, and the role of l-proline in alleviating kidney damage was investigated. In a 28-day toxicity mouse model, thirty mice were divided into six [...] Read more.

The toxicity and related mechanisms of aflatoxin B1 (AFB1) and aflatoxin M1 (AFM1) in the mouse kidney were studied, and the role of l-proline in alleviating kidney damage was investigated. In a 28-day toxicity mouse model, thirty mice were divided into six groups: control (without treatment), l-proline group (10 g/kg body weight (b.w.)), AFB1 group (0.5 mg/kg b.w.), AFM1 (3.5 mg/kg b.w.), AFB1 + l-proline group and AFM1 + l-proline group. Kidney index and biochemical indicators were detected, and pathological staining was observed. Using a human embryonic kidney 293 (HEK 293) cell model, cell apoptosis rate and apoptotic proteins expressions were detected. The results showed that AFB1 and AFM1 activated pathways related with oxidative stress and caused kidney injury; l-proline significantly alleviated abnormal expressions of biochemical parameters and pathological kidney damage, as well as excessive cell apoptosis in the AF-treated models. Moreover, proline dehydrogenase (PRODH) was verified to regulate the levels of l-proline and downstream apoptotic factors (Bax, Bcl-2, and cleaved Caspase-3) compared with the control (p < 0.05). In conclusion, l-proline could protect mouse kidneys from AFB1 and AFM1 through alleviating oxidative damage and decreasing downstream apoptosis, which deserves further research and development. Full article

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

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27 pages, 1034 KiB

Open AccessEditor’s ChoiceReview

Mycotoxins during the Processes of Nixtamalization and Tortilla Production

by Sara Schaarschmidt and Carsten Fauhl-Hassek

Toxins 2019, 11(4), 227; https://doi.org/10.3390/toxins11040227 - 16 Apr 2019

Cited by 52 | Viewed by 8388

Abstract

Tortillas are a traditional staple food in Mesoamerican cuisine, which have also become popular on a global level, e.g., for wraps or as snacks (tortilla chips). Traditional tortilla production includes alkaline cooking (nixtamalization) of maize kernels. This article summarizes the current knowledge on [...] Read more.

Tortillas are a traditional staple food in Mesoamerican cuisine, which have also become popular on a global level, e.g., for wraps or as snacks (tortilla chips). Traditional tortilla production includes alkaline cooking (nixtamalization) of maize kernels. This article summarizes the current knowledge on mycotoxin changes during the nixtamalization of maize and tortilla production. Upon nixtamalization, mycotoxins can be affected in different ways. On the one hand, the toxins can be physically removed during steeping and washing. On the other hand, mycotoxins might be degraded, modified, or released/bound in the matrix by high pH and/or high temperature. This also applies to the subsequent baking of tortillas. Many studies have shown reduced mycotoxin levels in alkali-cooked maize and in tortillas. Most of the available data relate to aflatoxins and fumonisins. The reduction (and detoxification) of aflatoxins during nixtamalization might, however, be partially reversed in acidic conditions. The loss of fumonisin concentrations is to some extent accompanied by hydrolyzation and by lower toxicity. However, some studies have indicated the potential formation of toxicologically relevant modified forms and matrix-associated fumonisins. More data are required to assess the influence of alkaline cooking regarding such modified forms, as well as mycotoxins other than aflatoxins/fumonisins. Full article

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

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10 pages, 981 KiB

Open AccessEditor’s ChoiceArticle

Occurrence of Mycotoxigenic Fusarium Species and Competitive Fungi on Preharvest Maize Ear Rot in Poland

by Karolina Gromadzka, Lidia Błaszczyk, Jerzy Chełkowski and Agnieszka Waśkiewicz

Toxins 2019, 11(4), 224; https://doi.org/10.3390/toxins11040224 - 15 Apr 2019

Cited by 19 | Viewed by 4992

Abstract

Maize has become one of the most important crops for food and feed production—both as a silage and crop residue worldwide. The present study aimed to identify the co-occurrence of Fusarium subglutinans, Fusarium verticillioides, Trichoderma atroviride, Sarocladium zeae, and Lecanicillium [...] Read more.

Maize has become one of the most important crops for food and feed production—both as a silage and crop residue worldwide. The present study aimed to identify the co-occurrence of Fusarium subglutinans, Fusarium verticillioides, Trichoderma atroviride, Sarocladium zeae, and Lecanicillium lecanii on maize ear rot. Further, the accumulation of mycotoxins as secondary metabolites of Fusarium spp. in maize ear samples was also analyzed. Maize ear samples were collected between 2014 and 2017 from two main maize growing areas in Poland (Greater Poland and Silesia region). A significant difference was found in the frequency of two main Fusarium spp. that infect maize ears, namely F. subglutinans and F. verticillioides. In addition to Fusarium spp. T. atroviride, S. zeae, and L. lecanii were also identified. T. atroviride species was found in 14% of maize samples examined between 2014 and 2017, particularly with a high percentage of Trichoderma spp. recorded in 2014, i.e., in 31% of samples. However, mycotoxin content (beauvericin and fumonisins) varied, depending on both the location and year of sampling. The interaction of fungi and insects inhabiting maize ear and kernel is very complex and not yet elucidated. Therefore, further research is required in this area. Full article

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

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13 pages, 3292 KiB

Open AccessEditor’s ChoiceArticle

An Attempt to Characterize the Ciguatoxin Profile in Seriola fasciata Causing Ciguatera Fish Poisoning in Macaronesia

by Pablo Estevez, David Castro, Ana Pequeño-Valtierra, José M. Leao, Oscar Vilariño, Jorge Diogène and Ana Gago-Martínez

Toxins 2019, 11(4), 221; https://doi.org/10.3390/toxins11040221 - 13 Apr 2019

Cited by 39 | Viewed by 4924

Abstract

Ciguatera Fish Poisoning is a worldwide concern caused by the consumption of fish contaminated with ciguatoxins not only in endemic regions in the Pacific Ocean or the Caribbean Sea but also in emerging areas of Macaronesia on the eastern Atlantic. The recent emergence [...] Read more.

Ciguatera Fish Poisoning is a worldwide concern caused by the consumption of fish contaminated with ciguatoxins not only in endemic regions in the Pacific Ocean or the Caribbean Sea but also in emerging areas of Macaronesia on the eastern Atlantic. The recent emergence of these toxins in other coastal areas worldwide, prompted the need for the characterization of the risk in these areas. This Ciguatera Fish Poisoning risk has been recently identified as a potential threat in subtropical areas of the Atlantic coast and scientific efforts are being focused in the identification and confirmation of the toxins involved in this potential risk. Neuroblastoma cell assay has been widely used for the evaluation of the toxicity in several marine biotoxin groups, and found to be a very useful tool for toxicity screening. LC-MS/MS has been also used for confirmatory purposes although the main limitation of the advances on LC-MS/MS development is due to commercial unavailability of reference materials and hampers method implementation and validation or even confirmation of the ciguatoxins (CTXs) responsible for the toxic profiles. While neuroblastoma cell assay (N2a) is typically used for toxicity screening as mentioned above, being necessary to confirm this N2a toxicity by LC-MS/MS, this study is designed using N2a as a tool to confirm the toxicity of the fractions obtained corresponding to potential CTXs analogues according to the analysis by LC-MS/MS. With this aim, an amberjack sample (Seriola fasciata) from Selvagen Islads (Portugal) and implicated in Ciguatera Fish Poisoning was analyzed by LC-MS/MS and Caribbean Ciguatoxins were found to be mainly responsible for the toxicity. N2a was used in this work as a tool to help in the confirmation of the toxicity of fractions obtained by HPLC. Caribbean Ciguatoxin-1 was found as the main analogue responsible for the N2a toxicity while three Caribbean Ciguatoxin-1 (C-CTX1) metabolites which contribute to the total toxicity were also identified. Full article

(This article belongs to the Special Issue Emerging Marine Biotoxins)

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21 pages, 1523 KiB

Open AccessEditor’s ChoiceArticle

Development and Validation of a Liquid Chromatography High-Resolution Mass Spectrometry Method for the Simultaneous Determination of Mycotoxins and Phytoestrogens in Plant-Based Fish Feed and Exposed Fish

by Amritha Johny, Christiane Kruse Fæste, André S. Bogevik, Gerd Marit Berge, Jorge M.O. Fernandes and Lada Ivanova

Toxins 2019, 11(4), 222; https://doi.org/10.3390/toxins11040222 - 13 Apr 2019

Cited by 22 | Viewed by 5830

Abstract

New protein sources in fish feed require the assessment of the carry-over potential of contaminants and anti-nutrients from feed ingredients into the fish, and the assessment of possible health risks for consumers. Presently, plant materials including wheat and legumes make up the largest [...] Read more.

New protein sources in fish feed require the assessment of the carry-over potential of contaminants and anti-nutrients from feed ingredients into the fish, and the assessment of possible health risks for consumers. Presently, plant materials including wheat and legumes make up the largest part of aquafeeds, so evaluation of the transfer capabilities of typical toxic metabolites from plant-infesting fungi and of vegetable phytoestrogens into fish products is of great importance. With the aim of facilitating surveillance of relevant mycotoxins and isoflavones, we have developed and validated a multi-analyte LC-HRMS/MS method that can be used to ensure compliance to set maximum levels in feed and fish. The method performance characteristics were determined, showing high specificity for all 25 targeted analytes, which included 19 mycotoxins and three isoflavones and their corresponding aglycons with sufficient to excellent sensitivities and uniform analytical linearity in different matrices. Depending on the availability of matching stable isotope-labelled derivates or similar-structure homologues, calibration curves were generated either by using internal standards or by matrix-matched external standards. Precision and recovery data were in the accepted range, although they varied between the different analytes. This new method was considered as fit-for-purpose and applied for the analysis of customised fish feed containing wheat gluten, soy, or pea protein concentrate as well as salmon and zebrafish fed on diets with these ingredients for a period of up to eight weeks. Only mycotoxin enniatin B, at a level near the limit of detection, and low levels of isoflavones were detected in the feed, demonstrating the effectiveness of maximum level recommendations and modern feed processing technologies in the Norwegian aquaculture industry. Consequently, carry-over into fish muscle was not observed, confirming that fillets from plant-fed salmon were safe for human consumption. Full article

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

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12 pages, 2700 KiB

Open AccessEditor’s ChoiceCommunication

Mycotoxin Decontamination Efficacy of Atmospheric Pressure Air Plasma

by Nataša Hojnik, Martina Modic, Gabrijela Tavčar-Kalcher, Janja Babič, James L. Walsh and Uroš Cvelbar

Toxins 2019, 11(4), 219; https://doi.org/10.3390/toxins11040219 - 12 Apr 2019

Cited by 56 | Viewed by 6476

Abstract

Mycotoxins, the toxic secondary metabolites of mould species, are a growing global concern, rendering almost 25% of all food produced unfit for human or animal consumption, thus placing immense pressure on the food supply chain. Cold Atmospheric pressure Plasma (CAP) represents a promising, [...] Read more.

Mycotoxins, the toxic secondary metabolites of mould species, are a growing global concern, rendering almost 25% of all food produced unfit for human or animal consumption, thus placing immense pressure on the food supply chain. Cold Atmospheric pressure Plasma (CAP) represents a promising, low-cost, and environmentally friendly means to degrade mycotoxins with negligible effect on the quality of food products. Despite this promise, the study of CAP-mediated mycotoxin degradation has been limited to a small subset of the vast number of mycotoxins that plague the food supply chain. This study explores the degradation of aflatoxins, trichothecenes, fumonisins, and zearalenone using CAP generated in ambient air. CAP treatment was found to reduce aflatoxins by 93%, trichothecenes by 90%, fumonisins by 93%, and zearalenone by 100% after 8 minutes exposure. To demonstrate the potential of CAP-mediated mycotoxin degradation against more conventional methods, its efficiency was compared against ultraviolet C (UVC) light irradiation. In all cases, CAP was found to be considerably more efficient than UVC, with aflatoxin G₁ and zearalenone being completely degraded, levels that could not be achieved using UVC irradiation. 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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16 pages, 1084 KiB

Open AccessEditor’s ChoiceArticle

Fumonisin Production by Fusarium verticillioides in Maize Genotypes Cultivated in Different Environments

by Oelton Ferreira Rosa Junior, Mateus Sunti Dalcin, Vitor L. Nascimento, Fernando Machado Haesbaert, Talita Pereira de Souza Ferreira, Rodrigo Ribeiro Fidelis, Renato de Almeida Sarmento, Raimundo Wagner de Souza Aguiar, Eugenio Eduardo de Oliveira and Gil Rodrigues dos Santos

Toxins 2019, 11(4), 215; https://doi.org/10.3390/toxins11040215 - 10 Apr 2019

Cited by 34 | Viewed by 5447

Abstract

Fumonisins are mycotoxins (MTs) produced mainly by the fungus Fusarium verticillioides, the main pathogens of maize which cause ear rot. The aim of this work was to evaluate some factors that may lead to high fumonisin production by F. verticillioides in maize [...] Read more.

Fumonisins are mycotoxins (MTs) produced mainly by the fungus Fusarium verticillioides, the main pathogens of maize which cause ear rot. The aim of this work was to evaluate some factors that may lead to high fumonisin production by F. verticillioides in maize grains, correlating the pathogen inoculation method with different genotypes grown in four Brazilian states. Experiments were conducted in 2015–2016 in maize crops from experimental maize fields located in four distinct states of Brazil. Results showed that contamination by fumonisin mycotoxins occurred even on symptomatic or asymptomatic grains. In all municipalities, the samples showed levels of fumonisin B1 that were higher than would be tolerable for the human consumption of corn products (the current tolerance limit for fumonisin is 1.5 μg g⁻¹). High severity of grains infected with F. verticillioides does not always show high concentrations of fumonisins. Environments with higher temperatures may influence the production of high concentrations of fumonisin in maize hybrids. Spray inoculation methods and inoculation at the center of spikes did not influence fumonisin concentrations. Results showed that the hybrids P3630H, P32R48 and P3250 presented higher disease severity, as well as higher mycotoxin levels in the studied locations with higher temperatures. Full article

(This article belongs to the Section Mycotoxins)

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18 pages, 3884 KiB

Open AccessEditor’s ChoiceArticle

Antimicrobial and Antibiofilm Effects of Peptides from Venom of Social Wasp and Scorpion on Multidrug-Resistant Acinetobacter baumannii

by Rogério Coutinho das Neves, Márcia Renata Mortari, Elisabeth Ferroni Schwartz, André Kipnis and Ana Paula Junqueira-Kipnis

Toxins 2019, 11(4), 216; https://doi.org/10.3390/toxins11040216 - 10 Apr 2019

Cited by 31 | Viewed by 5946

Abstract

Intravascular stent infection is a rare complication with a high morbidity and high mortality; bacteria from the hospital environment form biofilms and are often multidrug-resistant (MDR). Antimicrobial peptides (AMPs) have been considered as alternatives to bacterial infection treatment. We analyzed the formation of [...] Read more.

Intravascular stent infection is a rare complication with a high morbidity and high mortality; bacteria from the hospital environment form biofilms and are often multidrug-resistant (MDR). Antimicrobial peptides (AMPs) have been considered as alternatives to bacterial infection treatment. We analyzed the formation of the bacterial biofilm on the vascular stents and also tested the inhibition of this biofilm by AMPs to be used as treatment or coating. Antimicrobial activity and antibiofilm were tested with wasp (Agelaia-MPI, Polybia-MPII, Polydim-I) and scorpion (Con10 and NDBP5.8) AMPs against Acinetobacter baumannii clinical strains. A. baumannii formed a biofilm on the vascular stent. Agelaia-MPI and Polybia-MPII inhibited biofilm formation with bacterial cell wall degradation. Coating biofilms with polyethylene glycol (PEG 400) and Agelaia-MPI reduced 90% of A. baumannii adhesion on stents. The wasp AMPs Agelaia-MPI and Polybia-MPII had better action against MDR A. baumannii adherence and biofilm formation on vascular stents, preventing its formation and treating mature biofilm when compared to the other tested peptides. Full article

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

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26 pages, 1928 KiB

Open AccessEditor’s ChoiceReview

Roles of Shiga Toxins in Immunopathology

by Moo-Seung Lee and Vernon L. Tesh

Toxins 2019, 11(4), 212; https://doi.org/10.3390/toxins11040212 - 9 Apr 2019

Cited by 66 | Viewed by 12137

Abstract

Shigella species and Shiga toxin-producing Escherichia coli (STEC) are agents of bloody diarrhea that may progress to potentially lethal complications such as diarrhea-associated hemolytic uremic syndrome (D+HUS) and neurological disorders. The bacteria share the ability to produce virulence factors called Shiga toxins (Stxs). [...] Read more.

Shigella species and Shiga toxin-producing Escherichia coli (STEC) are agents of bloody diarrhea that may progress to potentially lethal complications such as diarrhea-associated hemolytic uremic syndrome (D+HUS) and neurological disorders. The bacteria share the ability to produce virulence factors called Shiga toxins (Stxs). Research over the past two decades has identified Stxs as multifunctional toxins capable of inducing cell stress responses in addition to their canonical ribotoxic function inhibiting protein synthesis. Notably, Stxs are not only potent inducers of cell death, but also activate innate immune responses that may lead to inflammation, and these effects may increase the severity of organ injury in patients infected with Stx-producing bacteria. In the intestines, kidneys, and central nervous system, excessive or uncontrolled host innate and cellular immune responses triggered by Stxs may result in sensitization of cells to toxin mediated damage, leading to immunopathology and increased morbidity and mortality in animal models (including primates) and human patients. Here, we review studies describing Stx-induced innate immune responses that may be associated with tissue damage, inflammation, and complement activation. We speculate on how these processes may contribute to immunopathological responses to the toxins. Full article

(This article belongs to the Special Issue Toxins and Immunology)

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13 pages, 929 KiB

Open AccessEditor’s ChoiceReview

The Key Role of Phosphate on Vascular Calcification

by Mario Cozzolino, Paola Ciceri, Andrea Galassi, Michela Mangano, Stefano Carugo, Irene Capelli and Giuseppe Cianciolo

Toxins 2019, 11(4), 213; https://doi.org/10.3390/toxins11040213 - 9 Apr 2019

Cited by 112 | Viewed by 11887

Abstract

Vascular calcification (VC) is common in dialysis and non-dialysis chronic kidney disease (CKD) patients, even in the early stage of the disease. For this reason, it can be considered a CKD hallmark. VC contributes to cardiovascular disease (CVD) and increased mortality among CKD [...] Read more.

Vascular calcification (VC) is common in dialysis and non-dialysis chronic kidney disease (CKD) patients, even in the early stage of the disease. For this reason, it can be considered a CKD hallmark. VC contributes to cardiovascular disease (CVD) and increased mortality among CKD patients, although it has not been proven. There are more than one type of VC and every form represents a marker of systemic vascular disease and is associated with a higher prevalence of CVD in CKD patients, as shown by several clinical studies. Major risk factors for VC in CKD include: Increasing age, dialysis vintage, hyperphosphatemia (particularly in the setting of intermittent or persistent hypercalcemia), and a positive net calcium and phosphate balance. Excessive oral calcium intake, including calcium-containing phosphate binders, increases the risk for VC. Moreover, it has been demonstrated that there is less VC progression with non-calcium-containing phosphate binders. Unfortunately, until now, a specific therapy to prevent progression or to facilitate regression of VC has been found, beyond careful attention to calcium and phosphate balance. Full article

(This article belongs to the Special Issue The Chronic Kidney Disease - Mineral Bone Disorder (CKD-MBD))

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14 pages, 3209 KiB

Open AccessEditor’s ChoiceArticle

Fluorescence Spectroscopic Investigation of Competitive Interactions between Quercetin and Aflatoxin B₁ for Binding to Human Serum Albumin

by Hongxia Tan, Lu Chen, Liang Ma, Shuang Liu, Hongyuan Zhou, Yuhao Zhang, Ting Guo, Wei Liu, Hongjie Dai and Yong Yu

Toxins 2019, 11(4), 214; https://doi.org/10.3390/toxins11040214 - 9 Apr 2019

Cited by 31 | Viewed by 5013

Abstract

Aflatoxin B₁ (AFB₁) is a highly toxic mycotoxin found worldwide in cereals, food, and animal feeds. AFB₁ binds to human serum albumin (HSA) with high affinity. In previous experiments, it has been revealed that reducing the binding rate of [...] Read more.

Aflatoxin B₁ (AFB₁) is a highly toxic mycotoxin found worldwide in cereals, food, and animal feeds. AFB₁ binds to human serum albumin (HSA) with high affinity. In previous experiments, it has been revealed that reducing the binding rate of AFB₁ with HSA could speed up the elimination rate of AFB₁. Therefore, we examined the ability of quercetin to compete with AFB₁ for binding HSA by fluorescence spectroscopy, synchronous spectroscopy, ultrafiltration studies, etc. It was shown that AFB₁ and quercetin bind to HSA in the same Sudlow site I (subdomain IIA), and the binding constant (K_a) of the quercetin-HSA complex is significantly stronger than the complex of AFB₁-HSA. Our data in this experiment showed that quercetin is able to remove the AFB₁ from HSA and reduce its bound fraction. This exploratory work may be of significance for studies in the future regarding decreasing its bound fraction and then increasing its elimination rate for detoxification. This exploratory study may initiate future epidemiological research designs to obtain further in vivo evidence of the long-term (potential protective) effects of competing substances on human patients. Full article

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

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15 pages, 1432 KiB

Open AccessEditor’s ChoiceArticle

Monoclonal Antibody Combinations Prevent Serotype A and Serotype B Inhalational Botulism in a Guinea Pig Model

by Milan T. Tomic, Yero Espinoza, Zachary Martinez, Khanh Pham, Ronald R. Cobb, Doris M. Snow, Christopher G. Earnhart, Traci Pals, Emily S. Syar, Nancy Niemuth, Dean J. Kobs, Shauna Farr-Jones and James D. Marks

Toxins 2019, 11(4), 208; https://doi.org/10.3390/toxins11040208 - 6 Apr 2019

Cited by 18 | Viewed by 5707

Abstract

Botulinum neurotoxins (BoNT) are some of the most toxic proteins known, with a human LD₅₀ of ~1 ng/kg. Equine antitoxin has a half-life in circulation of less than 1 day and is limited to a treatment rather than a prevention indication. The [...] Read more.

Botulinum neurotoxins (BoNT) are some of the most toxic proteins known, with a human LD₅₀ of ~1 ng/kg. Equine antitoxin has a half-life in circulation of less than 1 day and is limited to a treatment rather than a prevention indication. The development of monoclonal antibodies (mAbs) may represent an alternative therapeutic option that can be produced at high quantities and of high quality and with half-lives of >10 days. Two different three mAb combinations are being developed that specifically neutralize BoNT serotypes A (BoNT/A) and B (BoNT/B). We investigated the pharmacokinetics of the anti-BoNT/A and anti-BoNT/B antibodies in guinea pigs (Cavia porcellus) and their ability to protect guinea pigs against an aerosol challenge of BoNT/A1 or BoNT/B1. Each antibody exhibited dose-dependent exposure and reached maximum circulating concentrations within 48 h post intraperitoneal or intramuscular injection. A single intramuscular dose of the three mAb combination protected guinea pigs against an aerosol challenge dose of 93 LD₅₀ of BoNT/A1 and 116 LD₅₀ of BoNT/B1 at 48 h post antibody administration. These mAbs are effective in preventing botulism after an aerosol challenge of BoNT/A1 and BoNT/B1 and may represent an alternative to vaccination to prevent type A or B botulism in those at risk of BoNT exposure. Full article

(This article belongs to the Section Bacterial Toxins)

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11 pages, 379 KiB

Open AccessEditor’s ChoiceArticle

Exposure Assessment and Risk Characterization of Aflatoxin M1 Intake through Consumption of Milk and Yoghurt by Student Population in Serbia and Greece

by Bozidar Udovicki, Ilija Djekic, Eleni P. Kalogianni and Andreja Rajkovic

Toxins 2019, 11(4), 205; https://doi.org/10.3390/toxins11040205 - 5 Apr 2019

Cited by 60 | Viewed by 4438

Abstract

The objective of this research was to perform an exposure assessment of aflatoxin M1 (AFM1) intake through the consumption of milk and yoghurt by the student population in Serbia and Greece. A food consumption survey of milk and yoghurt was performed during the [...] Read more.

The objective of this research was to perform an exposure assessment of aflatoxin M1 (AFM1) intake through the consumption of milk and yoghurt by the student population in Serbia and Greece. A food consumption survey of milk and yoghurt was performed during the first half of 2018 in the two countries with at least 500 interviewees (aged between 18 and 27 years) per country, covering their dietary habits and body weight based on one-day and seven-day recall methods. Values for the concentration of AFM1 were extracted from published research. Finally, a Monte Carlo analysis of 100,000 iterations was performed to estimate the intake of AFM1 from the consumption of the two dairy products. Results revealed that the estimated average exposure of students to AFM1 was in the range of 1.238–2.674 ng kg⁻¹ bw day⁻¹ for Serbia, and 0.350–0.499 ng kg⁻¹ bw day⁻¹ for Greece, depending on the dietary recall method employed. High estimations for hepatocellular carcinoma (HCC) cases/year/10⁵ individuals, depending on the prevalence of Hepatitis B virus surface antigen positive individuals (HBsAg+), were 0.0036–0.0047 and 0.0007–0.0009 for Serbia and Greece, respectively. Presented Margin of Exposure (MOE) and Hazard Index (HI) values indicate increased risk from exposure to AFM1, particularly in Serbia. Full article

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

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15 pages, 1296 KiB

Open AccessEditor’s ChoiceArticle

Understanding the Significance of Biochemistry in the Storage, Handling, Purification, and Sampling of Amphiphilic Mycolactone

by Jessica Z. Kubicek-Sutherland, Dung M. Vu, Aaron S. Anderson, Timothy C. Sanchez, Paul J. Converse, Ricardo Martí-Arbona, Eric L. Nuermberger, Basil I. Swanson and Harshini Mukundan

Toxins 2019, 11(4), 202; https://doi.org/10.3390/toxins11040202 - 4 Apr 2019

Cited by 14 | Viewed by 4736

Abstract

Mycolactone, the amphiphilic macrolide toxin secreted by Mycobacterium ulcerans, plays a significant role in the pathology and manifestations of Buruli ulcer (BU). Consequently, it follows that the toxin is a suitable target for the development of diagnostics and therapeutics for this disease. [...] Read more.

Mycolactone, the amphiphilic macrolide toxin secreted by Mycobacterium ulcerans, plays a significant role in the pathology and manifestations of Buruli ulcer (BU). Consequently, it follows that the toxin is a suitable target for the development of diagnostics and therapeutics for this disease. Yet, several challenges have deterred such development. For one, the lipophilic nature of the toxin makes it difficult to handle and store and contributes to variability associated with laboratory experimentation and purification yields. In this manuscript, we have attempted to incorporate our understanding of the lipophilicity of mycolactone in order to define the optimal methods for the storage, handling, and purification of this toxin. We present a systematic correlation of variability associated with measurement techniques (thin-layer chromatography (TLC), mass spectrometry (MS), and UV-Vis spectrometry), storage conditions, choice of solvents, as well as the impact of each of these on toxin function as assessed by cellular cytotoxicity. We also compared natural mycolactone extracted from bacterial culture with synthesized toxins in laboratory (solvents, buffers) and physiologically relevant (serum) matrices. Our results point to the greater stability of mycolactone in organic, as well as detergent-containing, solvents, regardless of the container material (plastic, glass, or silanized tubes). They also highlight the presence of toxin in samples that may be undetectable by any one technique, suggesting that each detection approach captures different configurations of the molecule with varying specificity and sensitivity. Most importantly, our results demonstrate for the very first time that amphiphilic mycolactone associates with host lipoproteins in serum, and that this association will likely impact our ability to study, diagnose, and treat Buruli ulcers in patients. Full article

(This article belongs to the Special Issue Mycolactone: Lipid-Like Immunosuppressive Toxin of Buruli Ulcer)

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16 pages, 3749 KiB

Open AccessEditor’s ChoiceArticle

A New Topical Eye Drop Containing LyeTxI-b, A Synthetic Peptide Designed from A Lycosa erithrognata Venom Toxin, Was Effective to Treat Resistant Bacterial Keratitis

by Carolina Nunes da Silva, Flavia Rodrigues da Silva, Lays Fernanda Nunes Dourado, Pablo Victor Mendes dos Reis, Rummenigge Oliveira Silva, Bruna Lopes da Costa, Paula Santos Nunes, Flávio Almeida Amaral, Vera Lúcia dos Santos, Maria Elena de Lima and Armando da Silva Cunha Júnior

Toxins 2019, 11(4), 203; https://doi.org/10.3390/toxins11040203 - 4 Apr 2019

Cited by 27 | Viewed by 6361

Abstract

Bacterial keratitis is an ocular infection that can lead to severe visual disability. Staphylococcus aureus is a major pathogen of the eye. We recently demonstrated the strong antimicrobial activity of LyeTxI-b, a synthetic peptide derived from a Lycosa erithrognatha toxin. Herein, we evaluated [...] Read more.

Bacterial keratitis is an ocular infection that can lead to severe visual disability. Staphylococcus aureus is a major pathogen of the eye. We recently demonstrated the strong antimicrobial activity of LyeTxI-b, a synthetic peptide derived from a Lycosa erithrognatha toxin. Herein, we evaluated a topical formulation (eye drops) containing LyeTxI-b to treat resistant bacterial keratitis. Keratitis was induced with intrastromal injection of 4 × 10⁵ cells (4 µL) in New Zealand female white rabbits. Minimum inhibitory concentration (MIC) and biofilm viability were determined. LyeTxI-b ocular toxicity was evaluated through chorioallantoic membrane and Draize tests. One drop of the formulation (LyeTxI-b 28.9 µmol/L +0.5% CMC in 0.9% NaCl) was instilled into each eye four times a day, for a week. Slit-lamp biomicroscopy analysis, corneal histopathological studies and cellular infiltrate quantification through myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) detection were performed. LyeTxI-b was very effective in the treatment of keratitis, with no signs of ocular toxicity. Planktonic bacteria MIC was 3.6 µmol/L and LyeTxI-b treatment reduced biofilm viability in 90%. LyeTxI-b eliminated bacteria and reduced inflammatory cellular activity in the eyes. Healthy and treated animals showed similar NAG and MPO levels. LyeTxI-b is a potent new drug to treat resistant bacterial keratitis, showing effective antimicrobial and anti-inflammatory activity. Full article

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

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14 pages, 1352 KiB

Open AccessEditor’s ChoiceArticle

A Natural Variation of Fumonisin Gene Cluster Associated with Fumonisin Production Difference in Fusarium fujikuroi

by Sharmin Sultana, Miha Kitajima, Hironori Kobayashi, Hiroyuki Nakagawa, Masafumi Shimizu, Koji Kageyama and Haruhisa Suga

Toxins 2019, 11(4), 200; https://doi.org/10.3390/toxins11040200 - 3 Apr 2019

Cited by 20 | Viewed by 3767

Abstract

Fusarium fujikuroi, a member of the Fusarium fujikuroi species complex, stands out as a rice bakanae disease pathogen with a high production of gibberellic acid. Not all, but some F. fujikuroi strains are known to produce a carcinogenic mycotoxin fumonisin. Fumonisin biosynthesis [...] Read more.

Fusarium fujikuroi, a member of the Fusarium fujikuroi species complex, stands out as a rice bakanae disease pathogen with a high production of gibberellic acid. Not all, but some F. fujikuroi strains are known to produce a carcinogenic mycotoxin fumonisin. Fumonisin biosynthesis is dependent on the FUM cluster composed of 16 FUM genes. The FUM cluster was detected not only from a fumonisin producing strain, but also from a fumonisin nonproducing strain that does not produce a detectable level of fumonisin. Genetic mapping indicated the causative mutation(s) of fumonisin nonproduction is present in the FUM cluster of the fumonisin nonproducing strain. Comparative analyses of FUM genes between the fumonisin producing and the nonproducing strains and gene complementation indicated that causative mutation of fumonisin nonproduction is not a single occurrence and the mutations are distributed in FUM21 and FUM7. Our research revealed a natural variation in the FUM cluster involving fumonisin production difference in F. fujikuroi. Full article

(This article belongs to the Section Mycotoxins)

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16 pages, 3238 KiB

Open AccessEditor’s ChoiceArticle

The Pressure of Fusarium Disease and Its Relation with Mycotoxins in The Wheat Grain and Malt

by Valentina Spanic, Zvonimir Zdunic, Georg Drezner and Bojan Sarkanj

Toxins 2019, 11(4), 198; https://doi.org/10.3390/toxins11040198 - 2 Apr 2019

Cited by 27 | Viewed by 4250

Abstract

Fusarium head blight (FHB) is one of the most destructive wheat fungal diseases, causing yield loss, quality reduction, and accumulation of mycotoxins. The aim of this research was to summarize the occurrence of major Fusarium mycotoxins: deoxynivalenol (DON), 3-acetyldeoxynivalenol (3-AcDON), nivalenol (NIV), and [...] Read more.

Fusarium head blight (FHB) is one of the most destructive wheat fungal diseases, causing yield loss, quality reduction, and accumulation of mycotoxins. The aim of this research was to summarize the occurrence of major Fusarium mycotoxins: deoxynivalenol (DON), 3-acetyldeoxynivalenol (3-AcDON), nivalenol (NIV), and zearalenone (ZEN) in two consecutive years to search the relationship between disease incidence and severity with mycotoxins found in control and inoculated grains and corresponding malt. In addition, deoxynivalenol-3-glucoside (D3G) in one-year research was measured. Tested wheat varieties showed infection scores of 3% (‘U1’ and ‘Sirban Prolifik’) to 79% (‘Golubica’) for Type I resistance evaluation. There were few moderately resistant varieties in view of their areas under the disease progress curve, which can be considered Type III resistance (‘Sirban Prolifik’ and ‘U1’). According to the data quantified by LC–MS/MS, DON decreased in infected malt in comparison to corresponding grain, while ZEN occurred only in infected malt samples. Both 3-AcDON and NIV increased in inoculated malt in comparison to corresponding grain, due to a combination of plant metabolism and de novo synthesis by molds during malting. Based on the results, we can draw a few conclusions: the resistance to Fusarium decreased quantified concentrations of DON; ZEN gets synthetized during malting; unregulated 3-AcDON and NIV increase during malting; more resistant varieties have converted DON to D3G more successfully. Modified mycotoxins should be also included to legislation, since they could be transformed back to the corresponding mycotoxins under food processing conditions or during digestion. Full article

(This article belongs to the Section Mycotoxins)

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9 pages, 1140 KiB

Open AccessEditor’s ChoiceArticle

A Novel Modified Hydrated Sodium Calcium Aluminosilicate (HSCAS) Adsorbent Can Effectively Reduce T-2 Toxin-Induced Toxicity in Growth Performance, Nutrient Digestibility, Serum Biochemistry, and Small Intestinal Morphology in Chicks

by Jin-Tao Wei, Kun-Tan Wu, Hua Sun, Mahmoud Mohamed Khalil, Jie-Fan Dai, Ying Liu, Qiang Liu, Ni-Ya Zhang, De-Sheng Qi and Lv-Hui Sun

Toxins 2019, 11(4), 199; https://doi.org/10.3390/toxins11040199 - 2 Apr 2019

Cited by 40 | Viewed by 5074

Abstract

The objective of this study was to evaluate the ability of a modified hydrated sodium calcium aluminosilicate (HSCAS) adsorbent to reduce the toxicity of T-2 toxin in broilers. Ninety-six one-day-old male broilers were randomly allocated into four experimental groups with four replicates of [...] Read more.

The objective of this study was to evaluate the ability of a modified hydrated sodium calcium aluminosilicate (HSCAS) adsorbent to reduce the toxicity of T-2 toxin in broilers. Ninety-six one-day-old male broilers were randomly allocated into four experimental groups with four replicates of six birds each. The four groups, 1–4, received a basal diet (BD), a BD plus 6.0 mg/kg T-2 toxin, a BD plus 6.0 mg/kg T-2 toxin with 0.05% modified HSCAS adsorbent, and a BD plus 0.05% modified HSCAS adsorbent, respectively, for two weeks. Growth performance, nutrient digestibility, serum biochemistry, and small intestinal histopathology were analyzed. Compared to the control group, dietary supplementation of T-2 toxin decreased (p < 0.05) body weight gain, feed intake, and the feed conversion ratio by 11.4–31.8% during the whole experiment. It also decreased (p < 0.05) the apparent metabolic rates of crude protein, calcium, and total phosphorus by 14.9–16.1%. The alterations induced by T-2 toxin were mitigated (p < 0.05) by the supplementation of the modified HSCAS adsorbent. Meanwhile, dietary modified HSCAS adsorbent supplementation prevented (p < 0.05) increased serum aspartate aminotransferase by T-2 toxin at d 14. It also prevented (p < 0.05) T-2 toxin-induced morphological changes and damage in the duodenum, jejunum, and ileum of broilers. However, dietary supplementation of the modified HSCAS adsorbent alone did not affect (p > 0.05) any of these variables. In conclusion, these findings indicate that the modified HSCAS adsorbent could be used against T-2 toxin-induced toxicity in growth performance, nutrient digestibility, and hepatic and small intestinal injuries in chicks. Full article

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

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13 pages, 1159 KiB

Open AccessEditor’s ChoiceReview

Long-term Effects of Snake Envenoming

by Subodha Waiddyanatha, Anjana Silva, Sisira Siribaddana and Geoffrey K. Isbister

Toxins 2019, 11(4), 193; https://doi.org/10.3390/toxins11040193 - 31 Mar 2019

Cited by 106 | Viewed by 26100

Abstract

Long-term effects of envenoming compromise the quality of life of the survivors of snakebite. We searched MEDLINE (from 1946) and EMBASE (from 1947) until October 2018 for clinical literature on the long-term effects of snake envenoming using different combinations of search terms. We [...] Read more.

Long-term effects of envenoming compromise the quality of life of the survivors of snakebite. We searched MEDLINE (from 1946) and EMBASE (from 1947) until October 2018 for clinical literature on the long-term effects of snake envenoming using different combinations of search terms. We classified conditions that last or appear more than six weeks following envenoming as long term or delayed effects of envenoming. Of 257 records identified, 51 articles describe the long-term effects of snake envenoming and were reviewed. Disability due to amputations, deformities, contracture formation, and chronic ulceration, rarely with malignant change, have resulted from local necrosis due to bites mainly from African and Asian cobras, and Central and South American Pit-vipers. Progression of acute kidney injury into chronic renal failure in Russell’s viper bites has been reported in several studies from India and Sri Lanka. Neuromuscular toxicity does not appear to result in long-term effects. Endocrine anomalies such as delayed manifestation of hypopituitarism following Russell’s viper bites have been reported. Delayed psychological effects such as depressive symptoms, post-traumatic stress disorder and somatisation have been reported. Blindness due to primary and secondary effects of venom is a serious, debilitating effect. In general, the available studies have linked a clinical effect to a snakebite in retrospect, hence lacked accurate snake authentication, details of acute management and baseline data and are unable to provide a detailed picture of clinical epidemiology of the long-term effects of envenoming. In the future, it will be important to follow cohorts of snakebite patients for a longer period of time to understand the true prevalence, severity, clinical progression and risk factors of long-term effects of snake envenoming. Full article

(This article belongs to the Section Animal Venoms)

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11 pages, 1096 KiB

Open AccessEditor’s ChoiceArticle

Fate of Ergot Alkaloids during Laboratory Scale Durum Processing and Pasta Production

by Sheryl A. Tittlemier, Dainna Drul, Mike Roscoe, Dave Turnock, Dale Taylor and Bin Xiao Fu

Toxins 2019, 11(4), 195; https://doi.org/10.3390/toxins11040195 - 31 Mar 2019

Cited by 21 | Viewed by 4239

Abstract

The fate of ergot alkaloids during the milling of durum and subsequent production and cooking of pasta was examined. Durum samples containing varying amounts of ergot sclerotia (0.01–0.1% by mass) were milled, and all milling product was analyzed for 10 ergot alkaloids using [...] Read more.

The fate of ergot alkaloids during the milling of durum and subsequent production and cooking of pasta was examined. Durum samples containing varying amounts of ergot sclerotia (0.01–0.1% by mass) were milled, and all milling product was analyzed for 10 ergot alkaloids using liquid chromatography with tandem mass spectrometry. Spaghetti was prepared from the semolina obtained during milling. Ergocristine, ergocristinine, and ergotamine were the predominant ergot alkaloids observed in the milling fractions and spaghetti. Approximately 84% of the total ergot alkaloid mass of the whole grain durum resided in the milling product fractions associated with the outer kernel layers (bran, shorts, feeds). No consistent loss of ergot alkaloids was observed during the production or cooking of spaghetti. However, changes in the ratio of R- to S-enantiomers occurred during the milling and cooking of spaghetti. Products containing bran, shorts, and feeds, as well as cooked spaghetti, contained a higher proportion of the less biologically active S-enantiomers. The results of this study emphasize the need to monitor R- and S-enantiomers, and to consider food and feed products, as opposed to whole grain, when assessing any exposure of consumers to ergot alkaloids. Full article

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

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15 pages, 808 KiB

Open AccessEditor’s ChoiceArticle

Detection of Five Mycotoxins in Different Food Matrices in the Malaysian Market by Using Validated Liquid Chromatography Electrospray Ionization Triple Quadrupole Mass Spectrometry

by Ali Mohamed Ali Alsharif, Yeun-Mun Choo and Guan-Huat Tan

Toxins 2019, 11(4), 196; https://doi.org/10.3390/toxins11040196 - 31 Mar 2019

Cited by 28 | Viewed by 4780

Abstract

Mycotoxins are common food contaminants which cause poisoning and severe health risks to humans and animals. The present study applied chemometric approach in liquid chromatography-tandem mass spectrometry (LC-MS/MS) optimization for simultaneous determination of mycotoxins, i.e., aflatoxins B1, B2, G1, and G2, and ochratoxin [...] Read more.

Mycotoxins are common food contaminants which cause poisoning and severe health risks to humans and animals. The present study applied chemometric approach in liquid chromatography-tandem mass spectrometry (LC-MS/MS) optimization for simultaneous determination of mycotoxins, i.e., aflatoxins B1, B2, G1, and G2, and ochratoxin A. The validated quick, easy, cheap, effective, rugged, and safe (QuEChERS)-LC-MS/MS method was used to study the occurrence of mycotoxins in 120 food matrices. The recovery ranges from 81.94% to 101.67% with relative standard deviation (RSD) lesser than 11%. Through the developed method, aflatoxins were detected in raisin, pistachio, peanut, wheat flour, spice, and chili samples with concentration ranges from 0.45 to 16.93 µg/kg. Trace concentration of ochratoxin A was found in wheat flour and peanut samples which ranged from 1.2 to 3.53 µg/kg. Some of the tested food samples contained mycotoxins of above the European legal maximum limit. Full article

(This article belongs to the Section Mycotoxins)

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10 pages, 261 KiB

Open AccessEditor’s ChoiceArticle

Nasal Colonization of Humans with Occupational Exposure to Raw Meat and to Raw Meat Products with Methicillin-Susceptible and Methicillin-Resistant Staphylococcus aureus

by Christiane Cuny, Franziska Layer, Sonja Hansen, Guido Werner and Wolfgang Witte

Toxins 2019, 11(4), 190; https://doi.org/10.3390/toxins11040190 - 30 Mar 2019

Cited by 31 | Viewed by 3806

Abstract

Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) is widely disseminated as a nasal colonizer of conventionally raised livestock and of humans subjected to occupational exposure. Reports on contamination of raw meat raise the question as to whether occupationally exposed food handlers are at particular risk [...] Read more.

Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) is widely disseminated as a nasal colonizer of conventionally raised livestock and of humans subjected to occupational exposure. Reports on contamination of raw meat raise the question as to whether occupationally exposed food handlers are at particular risk of nasal colonization by LA-MRSA. Here, we report the results from a cross-sectional study on nasal S. aureus/MRSA colonization of butchers, meat sellers, and cooks in Germany. We sampled 286 butchers and meat sellers in 26 butcheries and 319 cooks handling meat in 16 professional canteen kitchens. Swabs were processed on both blood agar plates and MRSA-selective plates. MRSA were confirmed by PCR for mec genes and by broth microdilution. All isolates were subjected to molecular typing. PCR for markers useful to differentiate human-adapted and animal-adapted subpopulations was performed due to the presence of clonal complexes known to occur in both livestock and humans (CC5, CC7, CC8, CC9, and CC398). Only two participants (0.33%) were colonized by MRSA (Hospital-associated MRSA ST22). Nasal colonization by methicillin-susceptible S. aureus (MSSA) was detected in 16.6% of cooks and in 26.2% of butchers and meat sellers. Among 16 of the isolates attributed to CC7, three were negative for the immune evasion gene cluster, suggesting an animal origin. Isolates attributed to CC5, CC8, and CC398 were negative for markers typical of animal-adapted subpopulations. The occupational handling of raw meat and raw meat products was not associated with nasal colonization by LA-MRSA. Full article

(This article belongs to the Special Issue Methicillin-Resistant Staphylococci and Macrococci at the Interface of Human and Animal Health)

13 pages, 2169 KiB

Open AccessEditor’s ChoiceArticle

First Characterization of The Venom from Apis mellifera syriaca, A Honeybee from The Middle East Region

by Jacinthe Frangieh, Yahya Salma, Katia Haddad, Cesar Mattei, Christian Legros, Ziad Fajloun and Dany El Obeid

Toxins 2019, 11(4), 191; https://doi.org/10.3390/toxins11040191 - 30 Mar 2019

Cited by 51 | Viewed by 8050

Abstract

Bee venom is a mixture of several components with proven therapeutic benefits, among which are anti-inflammatory, analgesic, and various cardiovascular conditions. In this work, we analyzed for the first time the proteomic content and biological properties of the crude venom from Apis mellifera [...] Read more.

Bee venom is a mixture of several components with proven therapeutic benefits, among which are anti-inflammatory, analgesic, and various cardiovascular conditions. In this work, we analyzed for the first time the proteomic content and biological properties of the crude venom from Apis mellifera syriaca, a honeybee from the Middle East region. Using high-performance liquid chromatography-tandem mass spectrometry, we evidence the venom contains phospholipase A2, hyaluronidase, mast cell-degranulating peptide, adolapin, apamin, and melittin. The latter was purified by solid phase extraction method (SPE) and tested in parallel with crude venom for biological activities. Precisely, crude venom—but not melittin—exhibited antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa strains. Alongside, hemolytic activity was observed in human blood subjected to the venom at high doses. A. mellifera syriaca venom displayed antioxidant activities, and not surprisingly, PLA2 catalytic activity. Eventually, the venom proved to exert antiproliferative effects against MCF-7 and 3T3 cancer cells lines. This first report of a new bee venom opens new avenues for therapeutic uses of bee venoms. Full article

(This article belongs to the Special Issue Venom and Toxin as Targeted Therapy)

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18 pages, 4746 KiB

Open AccessEditor’s ChoiceArticle

Paralytic Shellfish Toxins in Surf Clams Mesodesma donacium during a Large Bloom of Alexandrium catenella Dinoflagellates Associated to an Intense Shellfish Mass Mortality

by Gonzalo Álvarez, Patricio A. Díaz, Marcos Godoy, Michael Araya, Iranzu Ganuza, Roberto Pino, Francisco Álvarez, José Rengel, Cristina Hernández, Eduardo Uribe and Juan Blanco

Toxins 2019, 11(4), 188; https://doi.org/10.3390/toxins11040188 - 29 Mar 2019

Cited by 57 | Viewed by 8235

Abstract

In late February 2016, a harmful algal bloom (HAB) of Alexandrium catenella was detected in southern Chiloé, leading to the banning of shellfish harvesting in an extended geographical area (~500 km). On April 24, 2016, this bloom produced a massive beaching (an accumulation [...] Read more.

In late February 2016, a harmful algal bloom (HAB) of Alexandrium catenella was detected in southern Chiloé, leading to the banning of shellfish harvesting in an extended geographical area (~500 km). On April 24, 2016, this bloom produced a massive beaching (an accumulation on the beach surface of dead or impaired organisms which were drifted ashore) of surf clams Mesodesma donacium in Cucao Bay, Chiloé. To determine the effect of paralytic shellfish poisoning (PSP) toxins in M. donacium, samples were taken from Cucao during the third massive beaching detected on May 3, 2016. Whole tissue toxicity evidence a high interindividual variability with values which ranged from 1008 to 8763 μg STX eq 100 g⁻¹ and with a toxin profile dominated by GTX3, GTX1, GTX2, GTX4, and neoSTX. Individuals were dissected into digestive gland (DG), foot (FT), adductor muscle (MU), and other body fractions (OBF), and histopathological and toxin analyses were carried out on the obtained fractions. Some pathological conditions were observed in gill and digestive gland of 40–50% of the individuals that correspond to hemocyte aggregation and haemocytic infiltration, respectively. The most toxic tissue was DG (2221 μg STX eq 100 g⁻¹), followed by OBF (710 μg STX eq 100 g⁻¹), FT (297 μg STX eq 100 g⁻¹), and MU (314 μg STX eq 100 g⁻¹). The observed surf clam mortality seems to have been mainly due to the desiccation caused by the incapability of the clams to burrow. Considering the available information of the monitoring program and taking into account that this episode was the first detected along the open coast of the Pacific Ocean in southern Chiloé, it is very likely that the M. donacium population from Cucao Bay has not had a recurrent exposition to A. catenella and, consequently, that it has not been subjected to high selective pressure for PSP resistance. However, more research is needed to determine the effects of PSP toxins on behavioral and physiological responses, nerve sensitivity, and genetic/molecular basis for the resistance or sensitivity of M. donacium. Full article

(This article belongs to the Special Issue Marine Biotoxins and Seafood Poisoning)

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28 pages, 6126 KiB

Open AccessEditor’s ChoiceArticle

Dinophysis Species and Diarrhetic Shellfish Toxins: 20 Years of Monitoring Program in Andalusia, South of Spain

by Raúl Fernández, Luz Mamán, David Jaén, Lourdes Fernández Fuentes, M. Asunción Ocaña and M. Mercedes Gordillo

Toxins 2019, 11(4), 189; https://doi.org/10.3390/toxins11040189 - 29 Mar 2019

Cited by 24 | Viewed by 4600

Abstract

In Andalusia, the official monitoring program for toxic phytoplankton and marine biotoxins was launched in 1994 to comply with European legislation. Since then, there have been numerous episodes of DST (Diarrhetic shellfish toxins) associated with the proliferation of Dinophysis species. This article reviews [...] Read more.

In Andalusia, the official monitoring program for toxic phytoplankton and marine biotoxins was launched in 1994 to comply with European legislation. Since then, there have been numerous episodes of DST (Diarrhetic shellfish toxins) associated with the proliferation of Dinophysis species. This article reviews two decades of time series data and assesses the effectiveness of the program established. The testing of lipophilic toxins and toxic phytoplankton is based on official methods harmonized and accredited since 2007 according to the standard UNE-EN-ISO 17025. The major species of Dinophysis identified were D. acuminata complex, D. caudata, D. acuta and D. fortii, with the main growth season being from early spring until the end of autumn. Both D. acuminata complex and D. acuta have been clearly associated with toxicity in molluscs. Despite the complexity of data obtained through monitoring programs, it is possible to provide early warning of potential health risks for most situations. This is the first report of Dinophysis species and their relation to DST events in a time series from Andalusia. Full article

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

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9 pages, 871 KiB

Open AccessEditor’s ChoiceCommunication

Optimized Analysis of Ergot Alkaloids in Rye Products by Liquid Chromatography-Fluorescence Detection Applying Lysergic Acid Diethylamide as an Internal Standard

by Iris Holderied, Michael Rychlik and Paul W. Elsinghorst

Toxins 2019, 11(4), 184; https://doi.org/10.3390/toxins11040184 - 28 Mar 2019

Cited by 21 | Viewed by 4479

Abstract

Analysis of ergot alkaloids remains a topic of importance and the European Food Safety Authority (EFSA) has encouraged laboratories to provide monitoring data for the further evaluation of their occurrence in food and feed. While LC-MS/MS has dominated developments in recent years, LC-FLD [...] Read more.

Analysis of ergot alkaloids remains a topic of importance and the European Food Safety Authority (EFSA) has encouraged laboratories to provide monitoring data for the further evaluation of their occurrence in food and feed. While LC-MS/MS has dominated developments in recent years, LC-FLD is still more widespread, especially in developing countries. To improve the analysis of ergot alkaloids by LC-FLD, we developed an improved protocol introducing lysergic acid diethylamide (LSD) for internal standardization. Several aspects such as the composition and pH of the extraction medium, type of sorbent and conditions applied for solid-phase extraction/clean-up, use of a keeper during final evaporation and the type of syringe filter used for filtration prior to injection were thoroughly investigated. Optimized conditions comprise extraction by ethyl acetate, methanol and 28% aqueous ammonia in combination with basic aluminum oxide for extract clean-up. Use of a keeper was found inappropriate as LC-FLD analysis was significantly affected by co-eluting keeper components. Similar observations were made with some of the investigated syringe filters, where polytetrafluoroethylene (PTFE) proved to be the most suitable. Validation and application of the optimized methodology to real samples provided limits of detection and quantification suitable for the evaluation of relevant ergot alkaloid contaminations in rye and bakery products with superior precision that was facilitated by the introduced internal standard, LSD. Full article

(This article belongs to the Section Mycotoxins)

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15 pages, 4338 KiB

Open AccessEditor’s ChoiceArticle

Arecoline Promotes Migration of A549 Lung Cancer Cells through Activating the EGFR/Src/FAK Pathway

by Chih-Hsiang Chang, Mei-Chih Chen, Te-Huan Chiu, Yu-Hsuan Li, Wan-Chen Yu, Wan-Ling Liao, Muhammet Oner, Chang-Tze Ricky Yu, Chun-Chi Wu, Tsung-Ying Yang, Chieh-Lin Jerry Teng, Kun-Yuan Chiu, Kun-Chien Chen, Hsin-Yi Wang, Chia-Herng Yue, Chih-Ho Lai, Jer-Tsong Hsieh and Ho Lin

Toxins 2019, 11(4), 185; https://doi.org/10.3390/toxins11040185 - 28 Mar 2019

Cited by 26 | Viewed by 6102

Abstract

Arecoline is the primary alkaloid in betel nuts, which are known as a risk factor for oral submucosal fibrosis and oral cancer. Lung cancer is a severe type of carcinoma with high cell motility that is difficult to treat. However, the detailed mechanisms [...] Read more.

Arecoline is the primary alkaloid in betel nuts, which are known as a risk factor for oral submucosal fibrosis and oral cancer. Lung cancer is a severe type of carcinoma with high cell motility that is difficult to treat. However, the detailed mechanisms of the correlation between Arecoline and lung cancer are not fully understood. Here, we investigated the effect of Arecoline on migration in lung cancer cell lines and its potential mechanism through the muscarinic acetylcholine receptor 3 (mAChR3)-triggered EGFR/Src/FAK pathway. Our results indicate that different concentrations of Arecoline treatment (10 µM, 20 µM, and 40 µM) significantly increased the cell migration ability in A549 and CL1-0 cells and promoted the formation of the filamentous actin (F-actin) cytoskeleton, which is a crucial element for cell migration. However, migration of H460, CL1-5, and H520 cell lines, which have a higher migration ability, was not affected by Arecoline treatment. The EGFR/c-Src/Fak pathway, which is responsible for cell migration, was activated by Arecoline treatment, and a decreased expression level of E-cadherin, which is an epithelial marker, was observed in Arecoline-treated cell lines. Blockade of the EGFR/c-Src/Fak pathway with the inhibitors of EGFR (Gefitinib) or c-Src (Dasatinib) significantly prevented Arecoline-promoted migration in A549 cells. Gefitinib or Dasatinib treatment significantly disrupted the Arecoline-induced localization of phospho-Y576-Fak during focal adhesion in A549 cells. Interestingly, Arecoline-promoted migration in A549 cells was blocked by a specific mAChR3 inhibitor (4-DAMP) or a neutralizing antibody of matrix metalloproteinase (MMP7 or Matrilysin). Taken together, our findings suggest that mAChR3 might play an essential role in Arecoline-promoted EGFR/c-Src/Fak activation and migration in an A549 lung cancer cell line. Full article

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

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13 pages, 1871 KiB

Open AccessEditor’s ChoiceArticle

Pink Bollworm Resistance to Bt Toxin Cry1Ac Associated with an Insertion in Cadherin Exon 20

by Ling Wang, Yuemin Ma, Xueqin Guo, Peng Wan, Kaiyu Liu, Shengbo Cong, Jintao Wang, Dong Xu, Yutao Xiao, Xianchun Li, Bruce E. Tabashnik and Kongming Wu

Toxins 2019, 11(4), 186; https://doi.org/10.3390/toxins11040186 - 28 Mar 2019

Cited by 33 | Viewed by 5116

Abstract

Insecticidal proteins from Bacillus thuringiensis (Bt) are widely used to control insect pests, but their efficacy is reduced when pests evolve resistance. We report on a novel allele (r16) of the cadherin gene (PgCad1) in pink bollworm (Pectinophora [...] Read more.

Insecticidal proteins from Bacillus thuringiensis (Bt) are widely used to control insect pests, but their efficacy is reduced when pests evolve resistance. We report on a novel allele (r16) of the cadherin gene (PgCad1) in pink bollworm (Pectinophora gossypiella) associated with resistance to Bt toxin Cry1Ac, which is produced by transgenic cotton. The r16 allele isolated from a field population in China has 1545 base pairs of a degenerate transposon inserted in exon 20 of PgCad1, which generates a mis-spliced transcript containing a premature stop codon. A strain homozygous for r16 had 300-fold resistance to Cry1Ac, 2.6-fold cross-resistance to Cry2Ab, and completed its life cycle on transgenic Bt cotton producing Cry1Ac. Inheritance of Cry1Ac resistance was recessive and tightly linked with r16. Compared with transfected insect cells expressing wild-type PgCad1, cells expressing r16 were less susceptible to Cry1Ac. Recombinant cadherin protein was transported to the cell membrane in cells transfected with the wild-type PgCad1 allele, but not in cells transfected with r16. Cadherin occurred on brush border membrane vesicles (BBMVs) in the midgut of susceptible larvae, but not resistant larvae. These results imply that the r16 allele mediates Cry1Ac resistance in pink bollworm by interfering with the localization of cadherin. Full article

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

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21 pages, 6464 KiB

Open AccessEditor’s ChoiceArticle

Biomarkers for Exposure as a Tool for Efficacy Testing of a Mycotoxin Detoxifier in Broiler Chickens and Pigs

by Marianne Lauwers, Siska Croubels, Ben Letor, Christos Gougoulias and Mathias Devreese

Toxins 2019, 11(4), 187; https://doi.org/10.3390/toxins11040187 - 28 Mar 2019

Cited by 36 | Viewed by 7022

Abstract

Applying post-harvest control measures such as adding mycotoxin detoxifying agents is a frequently-used mitigation strategy for mycotoxins. EFSA states that the efficacy of these detoxifiers needs to be tested using specific biomarkers for exposure. However, the proposed biomarkers for exposure are not further [...] Read more.

Applying post-harvest control measures such as adding mycotoxin detoxifying agents is a frequently-used mitigation strategy for mycotoxins. EFSA states that the efficacy of these detoxifiers needs to be tested using specific biomarkers for exposure. However, the proposed biomarkers for exposure are not further optimized for specific target species. Hence, the goal of this study was (a) to evaluate the most suitable biomarkers for deoxynivalenol (DON) and zearalenone (ZEN) in porcine plasma, urine and feces; and DON, aflatoxin B1 (AFB1) and ochratoxin A (OTA) in plasma and excreta of broiler chickens and (b) to determine the efficacy of a candidate detoxifier, as a proof-of-concept study. Therefore, a mixture of mycotoxins was administered as a single oral bolus with or without detoxifying agent. In accordance with literature AFB1, OTA, and DON-sulphate (DON-S) proved optimal biomarkers in broilers plasma and excreta whereas, in pigs DON-glucuronide (DON-GlcA) and ZEN-glucuronide (ZEN-GlcA) proved the optimal biomarkers in plasma, DON and ZEN-GlcA in urine and, ZEN in feces. A statistically significant reduction was seen between control and treatment group for both AFB1 and DON in broiler plasma, under administration of the mycotoxin blend and detoxifier dose studied suggesting thus, beneficial bioactivity. 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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