Previous Issue

E-Mail Alert

Add your e-mail address to receive forthcoming issues of this journal:

Journal Browser

Journal Browser

Table of Contents

Toxins, Volume 11, Issue 1 (January 2019)

  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Readerexternal link to open them.
View options order results:
result details:
Displaying articles 1-56
Export citation of selected articles as:
Open AccessArticle Simultaneous Lateral Flow Immunoassay for Multi-Class Chemical Contaminants in Maize and Peanut with One-Stop Sample Preparation
Toxins 2019, 11(1), 56; https://doi.org/10.3390/toxins11010056 (registering DOI)
Received: 26 December 2018 / Revised: 17 January 2019 / Accepted: 17 January 2019 / Published: 20 January 2019
PDF Full-text (3361 KB) | HTML Full-text | XML Full-text
Abstract
Multi-class chemical contaminants, such as pesticides and mycotoxins, are recognized as the major risk factors in agro products. It is thus necessary to develop rapid and simple sensing methods to fulfill the on-site monitoring of multi-class chemical contaminants with different physicochemical properties. Herein,
[...] Read more.
Multi-class chemical contaminants, such as pesticides and mycotoxins, are recognized as the major risk factors in agro products. It is thus necessary to develop rapid and simple sensing methods to fulfill the on-site monitoring of multi-class chemical contaminants with different physicochemical properties. Herein, a lateral flow immunoassay via time-resolved fluorescence was developed for the rapid, on-site, simultaneous, and quantitative sensing aflatoxin B1 (AFB1), zearalenone (ZEA), and chlorothalonil (CTN) in maize and peanut. The sample preparation was optimized to a single step, combining the grinding and extraction. Under optimal conditions, the sensing method lowered the limits of detection (LOD) to 0.16, 0.52, and 1.21 µg/kg in maize and 0.18, 0.57, and 1.47 µg/kg in peanut with an analytical range of 0.48–20, 1.56–200, and 3.63–300 µg/kg for AFB1, ZEA and CTN, respectively. The protocol could be completed within 15 min, including sample preparation and lateral flow immunoassay. The recovery range was 83.24–110.80%. An excellent correlation was observed between this approach and high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) for mycotoxins and gas chromatography-tandem mass spectrometry (GC-MS/MS) for pesticide in maize and peanut. This work could be applied in on-site multi-class sensing for food safety. Full article
(This article belongs to the Special Issue Advanced Methods for Mycotoxins Detection)
Figures

Figure 1

Open AccessArticle Differential Transcriptome Responses to Aflatoxin B1 in the Cecal Tonsil of Susceptible and Resistant Turkeys
Received: 7 December 2018 / Revised: 8 January 2019 / Accepted: 14 January 2019 / Published: 18 January 2019
Viewed by 101 | PDF Full-text (2562 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The nearly-ubiquitous food and feed-borne mycotoxin aflatoxin B1 (AFB1) is carcinogenic and mutagenic, posing a food safety threat to humans and animals. One of the most susceptible animal species known and thus a good model for characterizing toxicological pathways, is
[...] Read more.
The nearly-ubiquitous food and feed-borne mycotoxin aflatoxin B1 (AFB1) is carcinogenic and mutagenic, posing a food safety threat to humans and animals. One of the most susceptible animal species known and thus a good model for characterizing toxicological pathways, is the domesticated turkey (DT), a condition likely due, at least in part, to deficient hepatic AFB1-detoxifying alpha-class glutathione S-transferases (GSTAs). Conversely, wild turkeys (Eastern wild, EW) are relatively resistant to the hepatotoxic, hepatocarcinogenic and immunosuppressive effects of AFB1 owing to functional gene expression and presence of functional hepatic GSTAs. This study was designed to compare the responses in gene expression in the gastrointestinal tract between DT (susceptible phenotype) and EW (resistant phenotype) following dietary AFB1 challenge (320 ppb for 14 days); specifically in cecal tonsil which functions in both nutrient absorption and gut immunity. RNAseq and gene expression analysis revealed significant differential gene expression in AFB1-treated animals compared to control-fed domestic and wild birds and in within-treatment comparisons between bird types. Significantly upregulated expression of the primary hepatic AFB1-activating P450 (CYP1A5) as well as transcriptional changes in tight junction proteins were observed in AFB1-treated birds. Numerous pro-inflammatory cytokines, TGF-β and EGF were significantly down regulated by AFB1 treatment in DT birds and pathway analysis suggested suppression of enteroendocrine cells. Conversely, AFB1 treatment modified significantly fewer unique genes in EW birds; among these were genes involved in lipid synthesis and metabolism and immune response. This is the first investigation of the effects of AFB1 on the turkey gastro-intestinal tract. Results suggest that in addition to the hepatic transcriptome, animal resistance to this mycotoxin occurs in organ systems outside the liver, specifically as a refractory gastrointestinal tract. Full article
(This article belongs to the Special Issue Mycotoxins Exposure and Related Disease)
Figures

Graphical abstract

Open AccessArticle Regional Sub-Saharan Africa Total Diet Study in Benin, Cameroon, Mali and Nigeria Reveals the Presence of 164 Mycotoxins and Other Secondary Metabolites in Foods
Received: 22 December 2018 / Revised: 15 January 2019 / Accepted: 15 January 2019 / Published: 17 January 2019
Viewed by 148 | PDF Full-text (497 KB)
Abstract
In the framework of the first multi-centre Sub-Saharan Africa Total Diet Study (SSA-TDS), 2328 commonly consumed foods were purchased, prepared as consumed and pooled into 194 composite samples of cereals, tubers, legumes, vegetables, nuts and seeds, dairy, oils, beverages and miscellaneous. Those core
[...] Read more.
In the framework of the first multi-centre Sub-Saharan Africa Total Diet Study (SSA-TDS), 2328 commonly consumed foods were purchased, prepared as consumed and pooled into 194 composite samples of cereals, tubers, legumes, vegetables, nuts and seeds, dairy, oils, beverages and miscellaneous. Those core foods were tested for mycotoxins and other fungal, bacterial and plant secondary metabolites by liquid chromatography, coupled with tandem mass spectrometry. The highest aflatoxin concentrations were quantified in peanuts, peanut oil and maize. The mean concentration of the sum of aflatoxins AFB1, AFB2, AFG1 and AFG2 (AFtot) in peanut samples (56.4 µg/kg) exceeded EU (4 µg/kg) and Codex (15 µg/kg) standards. The AFtot concentration (max: 246.0 µg/kg) was associated with seasonal and geographic patterns and comprised, on average, 80% AFB1, the most potent aflatoxin. Although ochratoxin A concentrations rarely exceeded existing Codex standards, it was detected in unregulated foods. One palm oil composite sample contained 98 different metabolites, including 35.4 µg/kg of ochratoxin A. In total, 164 different metabolites were detected, with unspecific metabolites like asperglaucide, cyclo(L-pro-L-val), cyclo (L-pro-L-tyr), flavoglaucin, emodin and tryptophol occurring in more than 50% of composite samples. Aflatoxin B1 (AFB1), fumonisin B1 (FB1), sterigmatocystin (STC), ochratoxin A (OTA), citrinin (CIT) and many other secondary fungal metabolites are frequent co-contaminants in staple foods, such as maize and sorghum. Populations from North Cameroon and from Benin may, therefore, suffer chronic and simultaneous exposure to AFB1, FB1, STC, OTA and CIT, which are prevalent in their diet. Full article
(This article belongs to the Special Issue Application of LC-MS/MS in the Mycotoxins Studies)
Open AccessReview Toxin Neutralization Using Alternative Binding Proteins
Received: 15 December 2018 / Revised: 7 January 2019 / Accepted: 12 January 2019 / Published: 17 January 2019
Viewed by 163 | PDF Full-text (6180 KB) | HTML Full-text | XML Full-text
Abstract
Animal toxins present a major threat to human health worldwide, predominantly through snakebite envenomings, which are responsible for over 100,000 deaths each year. To date, the only available treatment against snakebite envenoming is plasma-derived antivenom. However, despite being key to limiting morbidity and
[...] Read more.
Animal toxins present a major threat to human health worldwide, predominantly through snakebite envenomings, which are responsible for over 100,000 deaths each year. To date, the only available treatment against snakebite envenoming is plasma-derived antivenom. However, despite being key to limiting morbidity and mortality among snakebite victims, current antivenoms suffer from several drawbacks, such as immunogenicity and high cost of production. Consequently, avenues for improving envenoming therapy, such as the discovery of toxin-sequestering monoclonal antibodies against medically important target toxins through phage display selection, are being explored. However, alternative binding protein scaffolds that exhibit certain advantages compared to the well-known immunoglobulin G scaffold, including high stability under harsh conditions and low cost of production, may pose as possible low-cost alternatives to antibody-based therapeutics. There is now a plethora of alternative binding protein scaffolds, ranging from antibody derivatives (e.g., nanobodies), through rationally designed derivatives of other human proteins (e.g., DARPins), to derivatives of non-human proteins (e.g., affibodies), all exhibiting different biochemical and pharmacokinetic profiles. Undeniably, the high level of engineerability and potentially low cost of production, associated with many alternative protein scaffolds, present an exciting possibility for the future of snakebite therapeutics and merit thorough investigation. In this review, a comprehensive overview of the different types of binding protein scaffolds is provided together with a discussion on their relevance as potential modalities for use as next-generation antivenoms. Full article
(This article belongs to the Special Issue Snakebite – From Science to Society. Selected papers)
Figures

Figure 1

Open AccessArticle Monitoring the Disulfide Bonds of Folding Isomers of Synthetic CTX A3 Polypeptide Using MS-Based Technology
Received: 29 November 2018 / Revised: 15 January 2019 / Accepted: 15 January 2019 / Published: 17 January 2019
Viewed by 122 | PDF Full-text (3366 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Native disulfide formation is crucial to the process of disulfide-rich protein folding in vitro. As such, analysis of the disulfide bonds can be used to track the process of the folding reaction; however, the diverse structural isomers interfere with characterization due to the
[...] Read more.
Native disulfide formation is crucial to the process of disulfide-rich protein folding in vitro. As such, analysis of the disulfide bonds can be used to track the process of the folding reaction; however, the diverse structural isomers interfere with characterization due to the non-native disulfide linkages. Previously, a mass spectrometry (MS) based platform coupled with peptide demethylation and an automatic disulfide bond searching engine demonstrated the potential to screen disulfide-linked peptides for the unambiguous assignment of paired cysteine residues of toxin components in cobra venom. The developed MS-based platform was evaluated to analyze the disulfide bonds of structural isomers during the folding reaction of synthetic cardiotoxin A3 polypeptide (syn-CTX A3), an important medical component in cobra venom. Through application of this work flow, a total of 13 disulfide-linked peptides were repeatedly identified across the folding reaction, and two of them were found to contain cysteine pairings, like those found in native CTX A3. Quantitative analysis of these disulfide-linked peptides showed the occurrence of a progressive disulfide rearrangement that generates a native disulfide bond pattern on syn-CTX A3 folded protein. The formation of these syn-CTX A3 folded protein reaches a steady level in the late stage of the folding reaction. Biophysical and cell-based assays showed that the collected syn-CTX A3 folded protein have a β-sheet secondary structure and cytotoxic activity similar to that of native CTX A3. In addition, the immunization of the syn-CTX A3 folded proteins could induce neutralization antibodies against the cytotoxic activity of native CTX A3. In contrast, these structure activities were poorly observed in the other folded isomers with non-native disulfide bonds. The study highlights the ability of the developed MS platform to assay isomers with heterogeneous disulfide bonds, providing insight into the folding mechanism of the bioactive protein generation. Full article
(This article belongs to the Section Animal Venoms)
Figures

Figure 1

Open AccessArticle Botulinum Neurotoxin Therapy for Lingual Dystonia Using an Individualized Injection Method Based on Clinical Features
Received: 14 December 2018 / Revised: 11 January 2019 / Accepted: 15 January 2019 / Published: 17 January 2019
Viewed by 120 | PDF Full-text (2322 KB) | HTML Full-text | XML Full-text
Abstract
Lingual dystonia is a debilitating type of oromandibular dystonia characterized by involuntary, often task-specific, contractions of the tongue muscle activated by speaking or eating. Botulinum neurotoxin (BoNT) has been used to treat lingual dystonia; however, it is known to cause serious complications, such
[...] Read more.
Lingual dystonia is a debilitating type of oromandibular dystonia characterized by involuntary, often task-specific, contractions of the tongue muscle activated by speaking or eating. Botulinum neurotoxin (BoNT) has been used to treat lingual dystonia; however, it is known to cause serious complications, such as dysphasia and aspiration. The purpose of this study was to evaluate the efficacy and adverse effects of individualized BoNT therapy for lingual dystonia. One-hundred-and-seventy-two patients (102 females and 70 males, mean age: 46.2 years) with lingual dystonia were classified into four subtypes based on symptoms of involuntary tongue movements: protrusion (68.6%), retraction (16.9%), curling (7.6%), and laterotrusion (7.0%). Patients were treated with BoNT injection into the genioglossus and/or intrinsic muscles via individualized submandibular and/or intraoral routes. Results were compared before and after BoNT therapy. Botulinum neurotoxin was injected in 136 patients (mean: 4.8 injections). Clinical sub-scores (mastication, speech, pain, and discomfort) in a disease-specific rating scale were reduced significantly (p < 0.001) after administration. Comprehensive improvement after BoNT injection, assessed using the rating scale, was 77.6%. The curling type (81.9%) showed the greatest improvement, while the retraction type showed the least improvement (67.9%). Mild and transient dysphasia occurred in 12.5% of patients (3.7% of total injections) but disappeared spontaneously within several days to two weeks. No serious side effects were observed. With careful diagnosis of subtypes and a detailed understanding of lingual muscle anatomy, individualized BoNT injection into dystonic lingual muscles can be effective and safe. Full article
(This article belongs to the Special Issue Botulinum Toxin Treatment of Movement Disorders)
Figures

Graphical abstract

Open AccessArticle Mass Spectrometry Analysis and Biological Characterization of the Predatory Ant Odontomachus monticola Venom and Venom Sac Components
Received: 5 December 2018 / Revised: 9 January 2019 / Accepted: 12 January 2019 / Published: 17 January 2019
Viewed by 117 | PDF Full-text (2534 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We previously identified 92 toxin-like peptides and proteins, including pilosulin-like peptides 1–6 from the predatory ant Odontomachus monticola, by transcriptome analysis. Here, to further characterize venom components, we analyzed the venom and venom sac extract by ESI-MS/MS with or without trypsin digestion
[...] Read more.
We previously identified 92 toxin-like peptides and proteins, including pilosulin-like peptides 1–6 from the predatory ant Odontomachus monticola, by transcriptome analysis. Here, to further characterize venom components, we analyzed the venom and venom sac extract by ESI-MS/MS with or without trypsin digestion and reducing agent. As the low-molecular-mass components, we found amino acids (leucine/isoleucine, phenylalanine, and tryptophan) and biogenic amines (histamine and tyramine) in the venom and venom sac extract. As the higher molecular mass components, we found peptides and proteins such as pilosulin-like peptides, phospholipase A2s, hyaluronidase, venom dipeptidyl peptidases, conotoxin-like peptide, and icarapin-like peptide. In addition to pilosulin-like peptides 1–6, we found three novel pilosulin-like peptides that were overlooked by transcriptome analysis. Moreover, pilosulin-like peptides 1–6 were chemically synthesized, and some of them displayed antimicrobial, hemolytic, and histamine-releasing activities. Full article
(This article belongs to the Special Issue Arthropod Venom Components and their Potential Usage)
Figures

Figure 1

Open AccessArticle Gut Microbiota Profiling of Aflatoxin B1-Induced Rats Treated with Lactobacillus casei Shirota
Received: 20 December 2018 / Accepted: 10 January 2019 / Published: 17 January 2019
Viewed by 115 | PDF Full-text (2819 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Aflatoxin B1 (AFB1) is a ubiquitous carcinogenic food contaminant. Gut microbiota is of vital importance for the host’s health, regrettably, limited studies have reported the effects of xenobiotic toxins towards gut microbiota. Thus, the present study aims to investigate the interactions between AFB1
[...] Read more.
Aflatoxin B1 (AFB1) is a ubiquitous carcinogenic food contaminant. Gut microbiota is of vital importance for the host’s health, regrettably, limited studies have reported the effects of xenobiotic toxins towards gut microbiota. Thus, the present study aims to investigate the interactions between AFB1 and the gut microbiota. Besides, an AFB1-binding microorganism, Lactobacillus casei Shirota (Lcs) was tested on its ability to ameliorate the changes on gut microbiota induced by AFB1. The fecal contents of three groups of rats included an untreated control group, an AFB1 group, as well as an Lcs + AFB1 group, were analyzed. Using the MiSeq platform, the PCR products of 16S rDNA gene extracted from the feces were subjected to next-generation sequencing. The alpha diversity index (Shannon) showed that the richness of communities increased significantly in the Lcs + AFB1 group compared to the control and AFB1 groups. Meanwhile, beta diversity indices demonstrated that AFB1 group significantly deviated from the control and Lcs + AFB1 groups. AFB1-exposed rats were especially high in Alloprevotella spp. abundance. Such alteration in the bacterial composition might give an insight on the interactions of AFB1 towards gut microbiota and how Lcs plays its role in detoxification of AFB1. Full article
(This article belongs to the Special Issue Mycotoxins Exposure and Related Disease)
Figures

Figure 1

Open AccessArticle Development of Indirect Competitive Enzyme-Linked Immunosorbent Assay to Detect Fusarium verticillioides in Poultry Feed Samples
Received: 14 December 2018 / Revised: 10 January 2019 / Accepted: 11 January 2019 / Published: 17 January 2019
Viewed by 137 | PDF Full-text (877 KB) | HTML Full-text | XML Full-text
Abstract
Fumonisins are a group of toxic secondary metabolites that are produced by Fusarium verticillioides which are associated with poultry health hazard and great economic losses. The objective of the present study was to develop an immunological method to detect F. verticillioides in poultry
[...] Read more.
Fumonisins are a group of toxic secondary metabolites that are produced by Fusarium verticillioides which are associated with poultry health hazard and great economic losses. The objective of the present study was to develop an immunological method to detect F. verticillioides in poultry feed samples. An indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) based on a polyclonal antibody against 67 kDa protein of the F. verticillioides 97K exoantigen was developed to detect this fungus. Antibody anti-67 kDa protein showed cross-reactivity against F. graminearum (2–7%) and F. sporotrichioides (10%), but no or low cross-reactivity against Aspergillus sp. and Penicillium sp. exoantigens. The detection limit for the 67 kDa protein of F. verticillioides was 29 ng/mL. Eighty-one poultry feed samples were analyzed for Fusarium sp. count, 67 kDa protein of F. verticillioides and fumonisin concentrations. Eighty of the 81 feed samples (98.6%) showed Fusarium sp. contamination (mean 6.2 x 104 CFU/g). Mean 67 kDa protein and fumonisin concentration in the poultry feed samples was 21.0 µg/g and 1.02 µg/g, respectively. The concentration of 67 kDa protein, as determined by ic-ELISA correlated positively (p < 0.05) with fumonisin levels (r = 0.76). These results suggest that this ic-ELISA has potential to detect F. verticillioides and predict fumonisin contamination in poultry feed samples. Full article
(This article belongs to the Special Issue Advanced Methods for Mycotoxins Detection)
Figures

Graphical abstract

Open AccessArticle Differences in Dialysis Efficacy Have Limited Effects on Protein-Bound Uremic Toxins Plasma Levels over Time
Received: 17 December 2018 / Revised: 11 January 2019 / Accepted: 13 January 2019 / Published: 16 January 2019
Viewed by 121 | PDF Full-text (1156 KB) | HTML Full-text | XML Full-text
Abstract
The protein-bound uremic toxins para-cresyl sulfate (pCS) and indoxyl sulfate (IS) are associated with cardiovascular disease in chronic renal failure, but the effect of different dialysis procedures on their plasma levels over time is poorly studied. The present prospective, randomized, cross-over trial tested
[...] Read more.
The protein-bound uremic toxins para-cresyl sulfate (pCS) and indoxyl sulfate (IS) are associated with cardiovascular disease in chronic renal failure, but the effect of different dialysis procedures on their plasma levels over time is poorly studied. The present prospective, randomized, cross-over trial tested dialysis efficacy and monitored pre-treatment pCS and IS concentrations in 15 patients on low-flux and high-flux hemodialysis and high-convective volume postdilution hemodiafiltration over six weeks each. Although hemodiafiltration achieved by far the highest toxin removal, only the mean total IS level was decreased at week three (16.6 ± 12.1 mg/L) compared to baseline (18.9 ± 13.0 mg/L, p = 0.027) and to low-flux dialysis (20.0 ± 12.7 mg/L, p = 0.021). At week six, the total IS concentration in hemodiafiltration reached the initial values again. Concentrations of free IS and free and total pCS remained unaltered. Highest beta2-microglobulin elimination in hemodiafiltration (p < 0.001) led to a persistent decrease of the plasma levels at week three and six (each p < 0.001). In contrast, absent removal in low-flux dialysis resulted in rising beta2-microglobulin concentrations (p < 0.001). In conclusion, this trial demonstrated that even large differences in instantaneous protein-bound toxin removal by current extracorporeal dialysis techniques may have only limited impact on IS and pCS plasma levels in the longer term. Full article
(This article belongs to the Section Uremic Toxins)
Figures

Figure 1

Open AccessArticle Effects of Ultrasound-Guided Administration of Botulinum Toxin (IncobotulinumtoxinA) in Patients with Lateral Epicondylitis
Received: 3 October 2018 / Revised: 7 January 2019 / Accepted: 11 January 2019 / Published: 15 January 2019
Viewed by 162 | PDF Full-text (1012 KB) | HTML Full-text | XML Full-text
Abstract
How effective and safe are incobotulinumtoxinA injections in adult patients with lateral epicondylitis refractory to other treatments? In this experimental study, ultrasound-guided incobotulinumtoxinA 10–30 U/muscle was injected into extensor carpi ulnaris, extensor digiti minimi, extensor digitorum longus and extensor carpi radialis brevis muscles.
[...] Read more.
How effective and safe are incobotulinumtoxinA injections in adult patients with lateral epicondylitis refractory to other treatments? In this experimental study, ultrasound-guided incobotulinumtoxinA 10–30 U/muscle was injected into extensor carpi ulnaris, extensor digiti minimi, extensor digitorum longus and extensor carpi radialis brevis muscles. Pain (visual analogue scale [VAS], 0 to 10 [no pain to severe pain]) and upper-limb functionality (QuickDASH scale, 0 to 100 [best to worst]), assessed at baseline, 1, 3 and 6 months post-treatment, were analysed using repeated-measures analysis of variance (ANOVA) and Tukey post-hoc tests. Secondary analyses stratifying patient population by sex and baseline VAS were performed. Adverse events were reported. Twenty-four patients (mean [standard deviation] age 46.8 years) were included. Compared with baseline, mean VAS and QuickDASH scores improved at all follow-ups (p < 0.001 and p = 0.001, respectively; repeated-measures ANOVA). Secondary analyses revealed significant differences between baseline and all follow-ups in the group with baseline VAS ≥ 6 and in males and females (all p < 0.05, Tukey post-hoc test). No adverse events, except for the expected third finger weakness, were reported. In conclusion, ultrasound-guided incobotulinumtoxinA injections may be an effective treatment for lateral epicondylitis in the appropriate patient population. Full article
(This article belongs to the Special Issue Botulinum Toxin Treatment of Movement Disorders)
Figures

Figure 1

Open AccessArticle Autophagy and Apoptosis Interact to Modulate T-2 Toxin-Induced Toxicity in Liver Cells
Received: 12 December 2018 / Revised: 9 January 2019 / Accepted: 11 January 2019 / Published: 15 January 2019
Viewed by 121 | PDF Full-text (3019 KB) | HTML Full-text | XML Full-text
Abstract
T-2 toxin is a mycotoxin generated by Fusarium species which has been shown to be highly toxic to human and animals. T-2 toxin induces apoptosis in various tissues/organs. Apoptosis and autophagy are two closely interconnected processes, which are important for maintaining physiological homeostasis
[...] Read more.
T-2 toxin is a mycotoxin generated by Fusarium species which has been shown to be highly toxic to human and animals. T-2 toxin induces apoptosis in various tissues/organs. Apoptosis and autophagy are two closely interconnected processes, which are important for maintaining physiological homeostasis as well as pathogenesis. Here, for the first time, we demonstrated that T-2 toxins induce autophagy in human liver cells (L02). We demonstrated that T-2 toxin induce acidic vesicular organelles formation, concomitant with the alterations in p62/SQSTM1 and LC3-phosphatidylethanolamine conjugate (LC3-II) and the enhancement of the autophagic flux. Using mRFP-GFP-LC3 by lentiviral transduction, we showed T-2 toxin-mediated lysosomal fusion and the formation of autophagosomes in L02 cells. The formation of autophagosomes was further confirmed by transmission electron microcopy. While T-2 toxin induced both autophagy and apoptosis, autophagy appears to be a leading event in the response to T-2 toxin treatment, reflecting its protective role in cells against cellular damage. Activating autophagy by rapamycin (RAPA) inhibited apoptosis, while suppressing autophagy by chloroquine greatly enhanced the T-2 toxin-induced apoptosis, suggesting the crosstalk between autophagy and apoptosis. Taken together, these results indicate that autophagy plays a role in protecting cells from T-2 toxin-induced apoptosis suggesting that autophagy may be manipulated for the alleviation of toxic responses induced by T-2 toxin. Full article
(This article belongs to the Special Issue Dietary Mycotoxin Exposure: Emerging Risks to Human Health)
Figures

Figure 1

Open AccessArticle Spatial and Temporal Variation in Paralytic Shellfish Toxin Production by Benthic Microseira (Lyngbya) wollei in a Freshwater New York Lake
Received: 3 December 2018 / Revised: 8 January 2019 / Accepted: 9 January 2019 / Published: 15 January 2019
Viewed by 276 | PDF Full-text (2079 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Butterfield Lake is a mesotrophic lake in New York State where residents and pets have experienced unexplained health issues. Microseira wollei (basionym Lyngbya wollei) was found at two of 15 sites in Butterfield Lake and analyzed for microcystins, anatoxins, cylindrospermopsins, and paralytic
[...] Read more.
Butterfield Lake is a mesotrophic lake in New York State where residents and pets have experienced unexplained health issues. Microseira wollei (basionym Lyngbya wollei) was found at two of 15 sites in Butterfield Lake and analyzed for microcystins, anatoxins, cylindrospermopsins, and paralytic shellfish poisoning toxins (PSTs). Only PSTs and trace levels of anatoxin-a were detected in these samples. This is the first published report of PSTs within a New York State lake. To evaluate the environmental and temporal drivers leading to the observed toxicity, PST content at the two sites was examined in detail. There were distinct differences in the total PST content, filament nutrient, filament chlorophyll, and relationship to environmental drivers between the sites, as well as distinct differences in the total PST content measured using different analytical techniques. A multivariate model containing site, temperature, and filament chlorophyll explained 85% of the variation in PSTs observed over the growing season. This work emphasizes the importance of proper site selection and choice of analytical technique in the development of monitoring programs to protect lake users from the occurrence of benthic cyanobacteria toxins. Full article
(This article belongs to the Special Issue Paralytic Shellfish Toxins)
Figures

Figure 1

Open AccessArticle The Individual and Combined Effects of the Cyanotoxins, Anatoxin-a and Microcystin-LR, on the Growth, Toxin Production, and Nitrogen Fixation of Prokaryotic and Eukaryotic Algae
Received: 11 November 2018 / Revised: 3 December 2018 / Accepted: 12 December 2018 / Published: 15 January 2019
Viewed by 161 | PDF Full-text (3362 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Globally, eutrophication and warming of aquatic ecosystems has increased the frequency and intensity of cyanobacterial blooms and their associated toxins, with the simultaneous detection of multiple cyanotoxins often occurring. Despite the co-occurrence of cyanotoxins such as microcystins and anatoxin-a (ATX) in water bodies,
[...] Read more.
Globally, eutrophication and warming of aquatic ecosystems has increased the frequency and intensity of cyanobacterial blooms and their associated toxins, with the simultaneous detection of multiple cyanotoxins often occurring. Despite the co-occurrence of cyanotoxins such as microcystins and anatoxin-a (ATX) in water bodies, their effects on phytoplankton communities are poorly understood. The individual and combined effects of microcystin-LR (MC-LR) and ATX on the cyanobacteria Microcystis spp., and Anabaena variabilis (a.k.a. Trichormus variabilis), and the chlorophyte, Selenastrum capricornutum were investigated in the present study. Cell density, chlorophyll-a content, and the maximum quantum efficiency of photosystem II (Fv/Fm) of Microcystis cells were generally lowered after exposure to ATX or MC-LR, while the combined treatment with MC-LR and ATX synergistically reduced the chlorophyll-a concentration of Microcystis strain LE-3. Intracellular levels of microcystin in Microcystis LE-3 significantly increased following exposure to MC-LR + ATX. The maximum quantum efficiency of photosystem II of Anabaena strain UTEX B377 declined during exposure to the cyanotoxins. Nitrogen fixation by Anabaena UTEX B377 was significantly inhibited by exposure to ATX, but was unaffected by MC-LR. In contrast, the combination of both cyanotoxins (MC-LR + ATX) caused a synergistic increase in the growth of S. capricornutum. While the toxins caused an increase in the activity of enzymes that scavenge reactive oxygen species in cyanobacteria, enzyme activity was unchanged or decreased in S. capricornutum. Collectively this study demonstrates that MC-LR and ATX can selectively promote and inhibit the growth and performance of green algae and cyanobacteria, respectively, and that the combined effect of these cyanotoxins was often more intense than their individual effects on some strains. This suggests that the release of multiple cyanotoxins in aquatic ecosystems, following the collapse of blooms, may influence the succession of plankton communities. Full article
(This article belongs to the Special Issue Harmful Algal Bloom Dynamics)
Figures

Figure 1

Open AccessArticle Bioactivity and Structural Properties of Novel Synthetic Analogues of the Protozoan Toxin Climacostol
Received: 12 December 2018 / Revised: 7 January 2019 / Accepted: 8 January 2019 / Published: 15 January 2019
Viewed by 170 | PDF Full-text (6858 KB) | HTML Full-text | XML Full-text
Abstract
Climacostol (5-[(2Z)-non-2-en-1-yl]benzene-1,3-diol) is a resorcinol produced by the protozoan Climacostomum virens for defence against predators. It exerts a potent antimicrobial activity against bacterial and fungal pathogens, inhibits the growth of several human and rodent tumour cells, and is now available by
[...] Read more.
Climacostol (5-[(2Z)-non-2-en-1-yl]benzene-1,3-diol) is a resorcinol produced by the protozoan Climacostomum virens for defence against predators. It exerts a potent antimicrobial activity against bacterial and fungal pathogens, inhibits the growth of several human and rodent tumour cells, and is now available by chemical synthesis. In this study, we chemically synthesized two novel analogues of climacostol, namely, 2-methyl-5 [(2Z)-non-2-en-1-yl]benzene-1,3-diol (AN1) and 5-[(2Z)-non-2-en-1-yl]benzene-1,2,3-triol (AN2), with the aim to increase the activity of the native toxin, evaluating their effects on prokaryotic and free-living protists and on mammalian tumour cells. The results demonstrated that the analogue bearing a methyl group (AN1) in the aromatic ring exhibited appreciably higher toxicity against pathogen microbes and protists than climacostol. On the other hand, the analogue bearing an additional hydroxyl group (AN2) in the aromatic ring revealed its ability to induce programmed cell death in protistan cells. Overall, the data collected demonstrate that the introduction of a methyl or a hydroxyl moiety to the aromatic ring of climacostol can effectively modulate its potency and its mechanism of action. Full article
(This article belongs to the Section Marine and Freshwater Toxins)
Figures

Graphical abstract

Open AccessArticle Osmotic-Adaptation Response of sakA/hogA Gene to Aflatoxin Biosynthesis, Morphology Development and Pathogenicity in Aspergillus flavus
Received: 23 November 2018 / Revised: 19 December 2018 / Accepted: 11 January 2019 / Published: 14 January 2019
Viewed by 171 | PDF Full-text (6252 KB) | HTML Full-text | XML Full-text
Abstract
Aspergillus flavus is one of the fungi from the big family of Aspergillus genus and it is capable of colonizing a large number of seed/crops and living organisms such as animals and human beings. SakA (also called hogA/hog1) is an integral
[...] Read more.
Aspergillus flavus is one of the fungi from the big family of Aspergillus genus and it is capable of colonizing a large number of seed/crops and living organisms such as animals and human beings. SakA (also called hogA/hog1) is an integral part of the mitogen activated protein kinase signal of the high osmolarity glycerol pathway. In this study, the AfsakA gene was deleted (∆AfsakA) then complemented (∆AfsakA::AfsakA) using homologous recombination and the osmotic stress was induced by 1.2 mol/L D-sorbital and 1.2 mol/L sodium chloride. The result showed that ∆AfsakA mutant caused a significant influence on conidial formation compared to wild-type and ∆AfsakA::AfsakA strains. It was also found that AfsakA responds to both the osmotic stress and the cell wall stress. In the absence of osmotic stress, ∆AfsakA mutant produced more sclerotia in contrast to other strains, whereas all strains failed to generate sclerotia under osmotic stress. Furthermore, the deletion of AfsakA resulted in the increase of Aflatoxin B1 production compared to other strains. The virulence assay on both maize kernel and peanut seeds showed that ∆AfsakA strain drastically produced more conidia and Aflatoxin B1 than wild-type and complementary strains. AfSakA-mCherry was located to the cytoplasm in the absence of osmotic stress, while it translocated to the nucleus upon exposure to the osmotic stimuli. This study provides new insights on the development and evaluation of aflatoxin biosynthesis and also provides better understanding on how to prevent Aspergillus infections which would be considered the first step towards the prevention of the seeds damages caused by A. flavus. Full article
(This article belongs to the Section Mycotoxins)
Figures

Figure 1

Open AccessArticle Effects of Two Fractions of Swietenia macrophylla and Catechin on Muscle Damage Induced by Bothrops Venom and PLA2
Received: 8 November 2018 / Revised: 4 January 2019 / Accepted: 7 January 2019 / Published: 14 January 2019
Viewed by 144 | PDF Full-text (2607 KB) | HTML Full-text | XML Full-text
Abstract
Plant natural products can attenuate the myonecrosis caused by Bothrops snake venom and their phospholipases A2 (PLA2). In this study, we evaluated the effects of two fractions (F4 and F6) from Swietenia macrophylla and purified catechin on the muscle damage
[...] Read more.
Plant natural products can attenuate the myonecrosis caused by Bothrops snake venom and their phospholipases A2 (PLA2). In this study, we evaluated the effects of two fractions (F4 and F6) from Swietenia macrophylla and purified catechin on the muscle damage caused by a myotoxic PLA2 from Colombian Bothrops asper venom (BaColPLA2) in mice and by Bothrops marmoratus venom from Brazil in mouse phrenic nerve-diaphragm muscle (PND) preparations in vitro. Male mice were injected with PLA2 (50 µg) in the absence or presence of F4, F6, and catechin, in the gastrocnemius muscle and then killed 3, 7, 14, and 28 h later for histopathological analysis of myonecrosis, leukocyte infiltration, and the presence of collagen. Fractions F4 and F6 (500 µg) and catechin (90 µg) significantly reduced the extent of necrosis at all-time intervals. These two fractions and catechin also attenuated the leukocyte infiltration on day 3, as did catechin on day 14. There was medium-to-moderate collagen deposition in all groups up to day 7, but greater deposition on days 14 and 28 in the presence of F6 and catechin. Bothrops marmoratus venom (100 µg/mL) caused slight (~25%) muscle facilitation after 10 min and weak neuromuscular blockade (~64% decrease in contractile activity after a 120-min incubation). Pre-incubation of venom with F4 or F6 abolished the facilitation, whereas catechin, which was itself facilitatory, did not. All three fractions attenuated the venom-induced decrease in muscle contractions. These findings indicate that fractions and catechin from S. macrophylla can reduce the muscle damage caused by Bothrops venom and PLA2. These fractions or their components could be useful for treating venom-induced local damage. Full article
(This article belongs to the Special Issue Discovery of Antibodies and Novel Antivenoms against Envenoming)
Figures

Graphical abstract

Open AccessArticle Intradermal Application of Crotamine Induces Inflammatory and Immunological Changes In Vivo
Received: 24 November 2018 / Revised: 9 January 2019 / Accepted: 9 January 2019 / Published: 14 January 2019
Viewed by 151 | PDF Full-text (1911 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Crotamine is a single-chain polypeptide with cell-penetrating properties, which is considered a promising molecule for clinical use. Nevertheless, its biosafety data are still scarce. Herein, we assessed the in vivo proinflammatory properties of crotamine, including its local effect and systemic serum parameters. Sixty
[...] Read more.
Crotamine is a single-chain polypeptide with cell-penetrating properties, which is considered a promising molecule for clinical use. Nevertheless, its biosafety data are still scarce. Herein, we assessed the in vivo proinflammatory properties of crotamine, including its local effect and systemic serum parameters. Sixty male Wistar rats were intradermically injected with 200, 400 and 800 µg crotamine and analyzed after 1, 3 and 7 days. Local effect of crotamine was assessed by determination of MPO and NAG activities, NO levels and angiogenesis. Systemic inflammatory response was assessed by determination of IL-10, TNF-α, CRP, NO, TBARS and SH groups. Crotamine induced macrophages and neutrophils chemotaxis as evidenced by the upregulation of both NAG (0.5–0.6 OD/mg) and MPO (0.1–0.2 OD/mg) activities, on the first and third day of analysis, respectively. High levels of NO were observed for all concentrations and time-points. Moreover, 800 μg crotamine resulted in serum NO (64.7 μM) and local tissue NO (58.5 μM) levels higher or equivalent to those recorded for their respective histamine controls (55.7 μM and 59.0 μM). Crotamine also induced a significant angiogenic response compared to histamine. Systemically, crotamine induced a progressive increase in serum CRP levels up to the third day of analysis (22.4–45.8 mg/mL), which was significantly greater than control values. Crotamine (400 μg) also caused an increase in serum TNF-α, in the first day of analysis (1095.4 pg/mL), however a significant increase in IL-10 (122.2 pg/mL) was also recorded for the same time-point, suggesting the induction of an anti-inflammatory effect. Finally, crotamine changed the systemic redox state by inducing gradual increase in serum levels of TBARS (1.0–1.8 μM/mL) and decrease in SH levels (124.7–19.5 μM/mL) throughout the experimental period of analysis. In summary, rats intradermally injected with crotamine presented local and systemic acute inflammatory responses similarly to histamine, which limits crotamine therapeutic use on its original form. Full article
(This article belongs to the Special Issue Toxins and Immunology)
Figures

Graphical abstract

Open AccessArticle Combined Effect of Light and Temperature on the Production of Saxitoxins in Cylindrospermopsis raciborskii Strains
Received: 2 December 2018 / Revised: 5 January 2019 / Accepted: 7 January 2019 / Published: 14 January 2019
Viewed by 276 | PDF Full-text (1261 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Cylindrospermopsis raciborskii is a potentially toxic freshwater cyanobacterium that can tolerate a wide range of light and temperature. Due to climatic changes, the interaction between light and temperature is studied in aquatic systems, but no study has addressed the effect of both variables
[...] Read more.
Cylindrospermopsis raciborskii is a potentially toxic freshwater cyanobacterium that can tolerate a wide range of light and temperature. Due to climatic changes, the interaction between light and temperature is studied in aquatic systems, but no study has addressed the effect of both variables on the saxitoxins production. This study evaluated the combined effect of light and temperature on saxitoxins production and cellular quota in C. raciborskii. Experiments were performed with three C. raciborskii strains in batch cultures under six light intensities (10, 40, 60, 100, 150, and 500 μmol of photons m−2 s−1) and four temperatures (15, 20, 25, and 30 °C). The growth of C. raciborskii strains was limited at lower temperatures and the maximum growth rates were obtained under higher light combined with temperatures equal or above 20 °C, depending on the strain. In general, growth was highest at 30 °C at the lower light intensities and equally high at 25 °C and 30 °C under higher light. Highest saxitoxins concentration and cell-quota occurred at 25 °C under high light intensities, but were much lower at 30 °C. Hence, increased temperatures combined with sufficient light will lead to higher C. raciborskii biomass, but blooms could become less toxic in tropical regions. Full article
(This article belongs to the Special Issue Paralytic Shellfish Toxins)
Figures

Figure 1

Open AccessArticle Mesoscale Dynamics and Niche Segregation of Two Dinophysis Species in Galician-Portuguese Coastal Waters
Received: 1 December 2018 / Revised: 28 December 2018 / Accepted: 31 December 2018 / Published: 14 January 2019
Viewed by 131 | PDF Full-text (5601 KB) | HTML Full-text | XML Full-text
Abstract
Blooms of Dinophysis acuminata occur every year in Galicia (northwest Spain), between spring and autumn. These blooms contaminate shellfish with lipophilic toxins and cause lengthy harvesting bans. They are often followed by short-lived blooms of Dinophysis acuta, associated with northward longshore transport,
[...] Read more.
Blooms of Dinophysis acuminata occur every year in Galicia (northwest Spain), between spring and autumn. These blooms contaminate shellfish with lipophilic toxins and cause lengthy harvesting bans. They are often followed by short-lived blooms of Dinophysis acuta, associated with northward longshore transport, at the end of the upwelling season. During the summers of 1989 and 1990, dense blooms of D. acuta developed in situ, initially co-occurring with D. acuminata and later with the paralytic shellfish toxin-producer Gymnodinium catenatum. Unexplored data from three cruises carried out before, during, and following autumn blooms (13–14, 27–28 September and 11–12 October) in 1990 showed D. acuta distribution in shelf waters within the 50 m and 130 m isobaths, delimited by the upwelling front. A joint review of monitoring data from Galicia and Portugal provided a mesoscale view of anomalies in SST and other hydroclimatic factors associated with a northward displacement of the center of gravity of D. acuta populations. At the microscale, re-examination of the vertical segregation of cell maxima in the light of current knowledge, improved our understanding of niche differentiation between the two species of Dinophysis. Results here improve local transport models and forecast of Dinophysis events, the main cause of shellfish harvesting bans in the most important mussel production area in Europe. Full article
(This article belongs to the Special Issue Dinophysis Toxins: Distribution, Fate in Shellfish and Impacts)
Figures

Graphical abstract

Open AccessReview Selection of Fusarium Trichothecene Toxin Genes for Molecular Detection Depends on TRI Gene Cluster Organization and Gene Function
Received: 21 November 2018 / Revised: 15 December 2018 / Accepted: 8 January 2019 / Published: 14 January 2019
Viewed by 148 | PDF Full-text (2366 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Food security is a global concern. Fusarium are among the most economically important fungal pathogens because they are ubiquitous, disease management remains a challenge, they produce mycotoxins that affect food and feed safety, and trichothecene mycotoxin production can increase the pathogenicity of some
[...] Read more.
Food security is a global concern. Fusarium are among the most economically important fungal pathogens because they are ubiquitous, disease management remains a challenge, they produce mycotoxins that affect food and feed safety, and trichothecene mycotoxin production can increase the pathogenicity of some Fusarium species depending on the host species. Although trichothecenes may differ in structure by their patterns of hydroxylation or acetylation, these small changes have a significant impact on toxicity and the biological activity of these compounds. Therefore, detecting and identifying which chemotype is present in a given population are important to predicting the specific toxins that may be produced and, therefore, to evaluating the risk of exposure. Due to the challenges of inducing trichothecene production by Fusarium isolates in vitro for subsequent chemical analysis, PCR assays using gene-specific primers, either singly or in combination, designed against specific genes of the trichothecene gene cluster of multiple species of Fusarium have been developed. The establishment of TRI genotypes that potentially correspond to a specific chemotype requires examination of an information and knowledge pipeline whose critical aspects in sequential order are: (i) understanding the TRI gene cluster organization which differs according to Fusarium species under study; (ii) knowledge of the re-arrangements to the core TRI gene cluster over evolutionary time, which also differs according to Fusarium species; (iii) the functions of the TRI genes in the biosynthesis of trichothecene analogs; and (iv) based on (i)–(iii), selection of appropriate target TRI gene(s) for primer design in PCR amplification for the Fusarium species under study. This review, therefore, explains this pipeline and its connection to utilizing TRI genotypes as a possible proxy to chemotype designation. Full article
(This article belongs to the Special Issue Recent Advances in Fusarium Research)
Figures

Figure 1

Open AccessArticle Content/Potency Assessment of Botulinum Neurotoxin Type-A by Validated Liquid Chromatography Methods and Bioassays
Received: 22 November 2018 / Revised: 28 December 2018 / Accepted: 10 January 2019 / Published: 12 January 2019
Viewed by 198 | PDF Full-text (756 KB) | HTML Full-text | XML Full-text
Abstract
Botulinum neurotoxin type-A (BoNTA) is one of the seven different serotypes (A to G) produced by Clostridium botulinum. A stability-indicating size-exclusion chromatography (SEC) method was developed and validated, and the specificity was confirmed by forced degradation study, interference of the excipients, and peaks
[...] Read more.
Botulinum neurotoxin type-A (BoNTA) is one of the seven different serotypes (A to G) produced by Clostridium botulinum. A stability-indicating size-exclusion chromatography (SEC) method was developed and validated, and the specificity was confirmed by forced degradation study, interference of the excipients, and peaks purity. The method was applied to assess the content and high-molecular-weight (HMW) forms of BoNTA in biopharmaceutical products, and the results were compared with those of the LD50 mouse bioassay, the T−47D cell culture assay, and the reversed-phase chromatography (RPC) method, giving mean values of 0.71% higher, 0.36% lower, and 0.87% higher, respectively. Aggregated forms showed significant effects on cytotoxicity, as well as a decrease in the bioactivity (p < 0.05). The employment of the proposed method in conjunction with the optimized analytical technologies for the analysis of the intact and altered forms of the biotechnology-derived medicines, in the correlation studies, enabled the demonstration of the capability of each one of the methods and allowed for great improvements, thereby assuring their safe and effective use. Full article
(This article belongs to the Special Issue Characterization and Quantitative Analysis of Botulinum Neurotoxin)
Figures

Figure 1

Open AccessReview Why Are Botulinum Neurotoxin-Producing Bacteria So Diverse and Botulinum Neurotoxins So Toxic?
Received: 14 November 2018 / Revised: 3 January 2019 / Accepted: 9 January 2019 / Published: 11 January 2019
Viewed by 178 | PDF Full-text (687 KB) | HTML Full-text | XML Full-text
Abstract
Botulinum neurotoxins (BoNTs) are the most lethal toxins among all bacterial, animal, plant and chemical poisonous compounds. Although a great effort has been made to understand their mode of action, some questions are still open. Why, and for what benefit, have environmental bacteria
[...] Read more.
Botulinum neurotoxins (BoNTs) are the most lethal toxins among all bacterial, animal, plant and chemical poisonous compounds. Although a great effort has been made to understand their mode of action, some questions are still open. Why, and for what benefit, have environmental bacteria that accidentally interact with their host engineered so diverse and so specific toxins targeting one of the most specialized physiological processes, the neuroexocytosis of higher organisms? The extreme potency of BoNT does not result from only one hyperactive step, but in contrast to other potent lethal toxins, from multi-step activity. The cumulative effects of the different steps, each having a limited effect, make BoNTs the most potent lethal toxins. This is a unique mode of evolution of a toxic compound, the high potency of which results from multiple steps driven by unknown selection pressure, targeting one of the most critical physiological process of higher organisms. Full article
(This article belongs to the Special Issue Toxins:10th Anniversary)
Figures

Figure 1

Open AccessArticle Safety of Corn and Corn-Based Products Intended for Human Consumption Concerning Fumonisins from a Brazilian Processing Plant
Received: 30 November 2018 / Revised: 30 December 2018 / Accepted: 4 January 2019 / Published: 10 January 2019
Viewed by 186 | PDF Full-text (1000 KB) | HTML Full-text | XML Full-text
Abstract
Brazil is one of the world’s largest corn producers and is a leader in exportation. Due to intense globalization, corn may be commercialized worldwide and the issue concerning the safety of corn-based products has become a topic of widespread international interest. Dietary exposure
[...] Read more.
Brazil is one of the world’s largest corn producers and is a leader in exportation. Due to intense globalization, corn may be commercialized worldwide and the issue concerning the safety of corn-based products has become a topic of widespread international interest. Dietary exposure evaluation is a relevant criterion for mycotoxin risk assessment. Thus, human exposure to fumonisins were assessed for corn grain and its derivatives (endosperm, cornmeal, and grits; n = 320) sampled from one of the large-scale corn processing plants in Brazil. The total probable daily intake (PDI) for fumonisins in Brazil was 96.9 ng kg−1 body weight day−1, which corresponds to 5% of the provisional maximum tolerable daily intake (PMTDI) of 2000 ng kg−1 b.w. day−1 for fumonisins. In countries that import Brazilian corn, the total PDI is lower in European countries (from 35.7 to 177 ng kg−1 b.w. day−1) and higher in Angola (1553 ng kg−1 b.w. day−1). Taking into account that dietary exposure in populations in Brazil and importing countries was low, the corn-based products were safe for human consumption regarding fumonisins, even for regions with high corn consumption. Full article
(This article belongs to the Special Issue Fungal Growth and Mycotoxins: Challenges for developing countries)
Figures

Graphical abstract

Open AccessArticle Generation of a Broadly Cross-Neutralizing Antibody Fragment against Several Mexican Scorpion Venoms
Received: 11 December 2018 / Revised: 3 January 2019 / Accepted: 3 January 2019 / Published: 10 January 2019
Viewed by 203 | PDF Full-text (2425 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The recombinant antibody fragments generated against the toxic components of scorpion venoms are considered a promising alternative for obtaining new antivenoms for therapy. Using directed evolution and site-directed mutagenesis, it was possible to generate a human single-chain antibody fragment with a broad cross-reactivity
[...] Read more.
The recombinant antibody fragments generated against the toxic components of scorpion venoms are considered a promising alternative for obtaining new antivenoms for therapy. Using directed evolution and site-directed mutagenesis, it was possible to generate a human single-chain antibody fragment with a broad cross-reactivity that retained recognition for its original antigen. This variant is the first antibody fragment that neutralizes the effect of an estimated 13 neurotoxins present in the venom of nine species of Mexican scorpions. This single antibody fragment showed the properties of a polyvalent antivenom. These results represent a significant advance in the development of new antivenoms against scorpion stings, since the number of components would be minimized due to their broad cross-neutralization capacity, while at the same time bypassing animal immunization. Full article
(This article belongs to the Special Issue Discovery of Antibodies and Novel Antivenoms against Envenoming)
Figures

Graphical abstract

Open AccessArticle Assessment of Toxigenic Fusarium Species and Their Mycotoxins in Brewing Barley Grains
Received: 14 November 2018 / Revised: 20 December 2018 / Accepted: 29 December 2018 / Published: 10 January 2019
Viewed by 182 | PDF Full-text (893 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Fusarium species threaten yield and quality of cereals worldwide due to their ability to produce mycotoxins and cause plant diseases. Trichothecenes and zearalenone are the most economically significant mycotoxins and are of particular concern in barley, maize and wheat. For this reason, the
[...] Read more.
Fusarium species threaten yield and quality of cereals worldwide due to their ability to produce mycotoxins and cause plant diseases. Trichothecenes and zearalenone are the most economically significant mycotoxins and are of particular concern in barley, maize and wheat. For this reason, the aim of this study was to characterize the Fusarium isolates from brewing barley and to assess deoxynivalenol and zearalenone contamination in grains. Characterization of the Fusarium strains was carried out by the phylogeny based on two loci (EF-1α and RPB2). Mycotoxin detection and quantification were performed by LC-MS. The results show that Fusarium was the predominant genus. Phylogenetic study demonstrated that the majority of the strains clustered within the Fusarium sambucinum species complex followed by the Fusarium tricinctum species complex. The results revealed high incidence of deoxynivalenol (DON) and zearalenone (ZEA) contamination (90.6% and 87.5%, respectively). It was observed that 86% of the samples contaminated with ZEA were above the limits set by the EU and Brazilian regulations. These results may highlight the importance of controlling Fusarium toxins in barley, mainly because of its use in the brewing industry and the resistance of various mycotoxins to food processing treatments. Full article
(This article belongs to the Special Issue Application of LC-MS/MS in the Mycotoxins Studies)
Figures

Figure 1

Open AccessArticle Effect of Compound Probiotics and Mycotoxin Degradation Enzymes on Alleviating Cytotoxicity of Swine Jejunal Epithelial Cells Induced by Aflatoxin B1 and Zearalenone
Received: 1 October 2018 / Revised: 19 December 2018 / Accepted: 24 December 2018 / Published: 10 January 2019
Viewed by 293 | PDF Full-text (1067 KB) | HTML Full-text | XML Full-text
Abstract
Zearalenone (ZEA) and aflatoxin B1 (AFB1) are two main kinds of mycotoxins widely existing in grain and animal feed that cause a lot of economic loss and health problems for animals and humans. In order to alleviate the cytotoxic effects
[...] Read more.
Zearalenone (ZEA) and aflatoxin B1 (AFB1) are two main kinds of mycotoxins widely existing in grain and animal feed that cause a lot of economic loss and health problems for animals and humans. In order to alleviate the cytotoxic effects of AFB1 and ZEA on swine jejunal epithelial cells (IPEC-J2), the combination of a cell-free supernatant of compound probiotics (CFSCP) with mycotoxin degradation enzymes (MDEs) from Aspergillus oryzae was tested. The results demonstrated that coexistence of AFB1 and ZEA had synergetic toxic effects on cell viability. The cell viability was decreased with mycotoxin concentrations increasing, but increased with incubation time extension. The necrotic cell rates were increased when 40 µg/L AFB1 and/or 500 µg/L ZEA were added, but the addition of CFSCP + MDE suppressed the necrotic effects of AFB1 + ZEA. The viable cell rates were decreased when AFB1 and/or ZEA were added: However, the addition of CFSCP + MDE recovered them. The relative mRNA abundances of Bcl-2, occludin, and ZO-1 genes were significantly upregulated, while Bax, caspase-3, GLUT2, ASCT2, PepT1, and IL6 genes were significantly downregulated by CFSCP + MDE addition, compared to the groups containing 40 µg/L AFB1 and 500 µg/L ZEA. This research provided an effective strategy in alleviating mycotoxin cytotoxicity and keeping normal intestinal cell structure and animal health. Full article
Figures

Figure 1

Open AccessReview Multi-(myco)toxins in Malting and Brewing By-Products
Received: 11 December 2018 / Revised: 3 January 2019 / Accepted: 4 January 2019 / Published: 9 January 2019
Viewed by 200 | PDF Full-text (1585 KB) | HTML Full-text | XML Full-text
Abstract
Fungi, yeasts, and bacteria are common microorganisms on cereals used in malting and brewing industries. These microorganisms are mostly associated with the safety and quality of malt and beer, but also with the health safety of by-products used in animal nutrition. The real
[...] Read more.
Fungi, yeasts, and bacteria are common microorganisms on cereals used in malting and brewing industries. These microorganisms are mostly associated with the safety and quality of malt and beer, but also with the health safety of by-products used in animal nutrition. The real problem is their harmful metabolites—toxins that, due to their thermostable properties, can easily be transferred to malting and brewing by-products. Besides fungal metabolites, other toxins originating from plants can be harmful to animal health. Precise and accurate analytical techniques broadened the spectrum of known toxins originating from microorganisms and plants that can pose a threat to animal health. Multi-(myco)toxin analyses are advanced and useful tools for the assessment of product safety, and legislation should follow up and make some important changes to regulate yet unregulated, but highly occurring, microbial and plant toxins in malting and brewing by-products used for animal feed. Full article
(This article belongs to the Special Issue Food Safety and Natural Toxins)
Figures

Graphical abstract

Open AccessArticle Toxin ζ Reduces the ATP and Modulates the Uridine Diphosphate-N-acetylglucosamine Pool
Received: 4 December 2018 / Revised: 21 December 2018 / Accepted: 4 January 2019 / Published: 9 January 2019
Viewed by 205 | PDF Full-text (3000 KB) | HTML Full-text | XML Full-text
Abstract
Toxin ζ expression triggers a reversible state of dormancy, diminishes the pool of purine nucleotides, promotes (p)ppGpp synthesis, phosphorylates a fraction of the peptidoglycan precursor uridine diphosphate-N-acetylglucosamine (UNAG), leading to unreactive UNAG-P, induces persistence in a reduced subpopulation, and sensitizes cells to different
[...] Read more.
Toxin ζ expression triggers a reversible state of dormancy, diminishes the pool of purine nucleotides, promotes (p)ppGpp synthesis, phosphorylates a fraction of the peptidoglycan precursor uridine diphosphate-N-acetylglucosamine (UNAG), leading to unreactive UNAG-P, induces persistence in a reduced subpopulation, and sensitizes cells to different antibiotics. Here, we combined computational analyses with biochemical experiments to examine the mechanism of toxin ζ action. Free ζ toxin showed low affinity for UNAG. Toxin ζ bound to UNAG hydrolyzed ATP·Mg2+, with the accumulation of ADP, Pi, and produced low levels of phosphorylated UNAG (UNAG-P). Toxin ζ, which has a large ATP binding pocket, may temporally favor ATP binding in a position that is distant from UNAG, hindering UNAG phosphorylation upon ATP hydrolysis. The residues D67, E116, R158 and R171, involved in the interaction with metal, ATP, and UNAG, were essential for the toxic and ATPase activities of toxin ζ; whereas the E100 and T128 residues were partially dispensable. The results indicate that ζ bound to UNAG reduces the ATP concentration, which indirectly induces a reversible dormant state, and modulates the pool of UNAG. Full article
(This article belongs to the Special Issue Toxin-antitoxin (TA) systems)
Figures

Graphical abstract

Open AccessEditorial Acknowledgement to Reviewers of Toxins in 2018
Published: 9 January 2019
Viewed by 171 | PDF Full-text (323 KB) | HTML Full-text | XML Full-text
Abstract
Rigorous peer-review is the corner-stone of high-quality academic publishing [...] Full article
Toxins EISSN 2072-6651 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top