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Toxins, Volume 11, Issue 11 (November 2019)

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Open AccessReview
Hemolysis Derived Products Toxicity and Endothelium: Model of the Second Hit
Toxins 2019, 11(11), 660; https://doi.org/10.3390/toxins11110660 (registering DOI) - 13 Nov 2019
Abstract
Vascular diseases are multifactorial, often requiring multiple challenges, or ‘hits’, for their initiation. Intra-vascular hemolysis illustrates well the multiple-hit theory where a first event lyses red blood cells, releasing hemolysis-derived products, in particular cell-free heme which is highly toxic for the endothelium. Physiologically, [...] Read more.
Vascular diseases are multifactorial, often requiring multiple challenges, or ‘hits’, for their initiation. Intra-vascular hemolysis illustrates well the multiple-hit theory where a first event lyses red blood cells, releasing hemolysis-derived products, in particular cell-free heme which is highly toxic for the endothelium. Physiologically, hemolysis derived-products are rapidly neutralized by numerous defense systems, including haptoglobin and hemopexin which scavenge hemoglobin and heme, respectively. Likewise, cellular defense mechanisms are involved, including heme-oxygenase 1 upregulation which metabolizes heme. However, in cases of intra-vascular hemolysis, those systems are overwhelmed. Heme exerts toxic effects by acting as a damage-associated molecular pattern and promoting, together with hemoglobin, nitric oxide scavenging and ROS production. In addition, it activates the complement and the coagulation systems. Together, these processes lead to endothelial cell injury which triggers pro-thrombotic and pro-inflammatory phenotypes. Moreover, among endothelial cells, glomerular ones display a particular susceptibility explained by a weaker capacity to counteract hemolysis injury. In this review, we illustrate the ‘multiple-hit’ theory through the example of intra-vascular hemolysis, with a particular focus on cell-free heme, and we advance hypotheses explaining the glomerular susceptibility observed in hemolytic diseases. Finally, we describe therapeutic options for reducing endothelial injury in hemolytic diseases. Full article
(This article belongs to the Special Issue The Endothelial Effects of Uremic Toxins)
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Open AccessArticle
Comparative In Vitro Assessment of a Range of Commercial Feed Additives with Multiple Mycotoxin Binding Claims
Toxins 2019, 11(11), 659; https://doi.org/10.3390/toxins11110659 (registering DOI) - 12 Nov 2019
Abstract
Contamination of animal feed with multiple mycotoxins is an ongoing and growing issue, as over 60% of cereal crops worldwide have been shown to be contaminated with mycotoxins. The present study was carried out to assess the efficacy of commercial feed additives sold [...] Read more.
Contamination of animal feed with multiple mycotoxins is an ongoing and growing issue, as over 60% of cereal crops worldwide have been shown to be contaminated with mycotoxins. The present study was carried out to assess the efficacy of commercial feed additives sold with multi-mycotoxin binding claims. Ten feed additives were obtained and categorised into three groups based on their main composition. Their capacity to simultaneously adsorb deoxynivalenol (DON), zearalenone (ZEN), fumonisin B1 (FB1), ochratoxin A (OTA), aflatoxin B1 (AFB1) and T-2 toxin was assessed and compared using an in vitro model designed to simulate the gastrointestinal tract of a monogastric animal. Results showed that only one product (a modified yeast cell wall) effectively adsorbed more than 50% of DON, ZEN, FB1, OTA, T-2 and AFB1, in the following order: AFB1 > ZEN > T-2 > DON > OTA > FB1. The remaining products were able to moderately bind AFB1 (44–58%) but had less, or in some cases, no effect on ZEN, FB1, OTA and T-2 binding (<35%). It is important for companies producing mycotoxin binders that their products undergo rigorous trials under the conditions which best mimic the environment that they must be active in. Claims on the binding efficiency should only be made when such data has been generated. Full article
Open AccessArticle
Multiple Mycotoxins Determination in Food by LC-MS/MS: An International Collaborative Study
Toxins 2019, 11(11), 658; https://doi.org/10.3390/toxins11110658 (registering DOI) - 12 Nov 2019
Abstract
An intercollaborative study was organized to evaluate the performance characteristics of a liquid chromatography tandem mass spectrometry procedure for the simultaneous determination of 12 mycotoxins in food, which were ochratoxin A, aflatoxins B1, B2, G1, G2, and M1, deoxynivalenol, zearalenone, fumonisins B1 and [...] Read more.
An intercollaborative study was organized to evaluate the performance characteristics of a liquid chromatography tandem mass spectrometry procedure for the simultaneous determination of 12 mycotoxins in food, which were ochratoxin A, aflatoxins B1, B2, G1, G2, and M1, deoxynivalenol, zearalenone, fumonisins B1 and B2, and T-2 and HT-2 toxins. The method combined the simplicity of the QuEChERS (Quick, Easy, Cheap, Efficient, Rugged and Safe) approach with the efficiency of immunoaffinity column cleanup (the step used to enhance sensitivity and sample cleanup for some matrices only). Twenty-three entities were enrolled and were European reference laboratories for mycotoxin analysis, U.S. and European service laboratories, and Nestlé laboratories. Each participant analyzed 28 incurred and/or spiked blind samples composed of spices, nuts, milk powder, dried fruits, cereals, and baby food using the protocol given. Method performances were assessed according to ISO 5725-2. Relative standard deviations of repeatability and reproducibility and trueness values for each of the 115 mycotoxin/sample combinations ranged from 5% to 23%, 7% to 26%, and 85% to 129%, respectively, in line with requirements defined in EC 401/2006. The overall set of data gathered demonstrated that the method offered a unique platform to ensure compliance with EC 1881/2006 and EC 165/2013 regulations setting maximum limits for mycotoxins in food samples, even at low regulated levels for foods intended for infants and young children. The method was applicable regardless of the food, the regulated mycotoxin, and the concentration level, and thus is an excellent candidate for future standardization. Full article
(This article belongs to the Special Issue Application of LC-MS/MS in the Mycotoxins Studies)
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Open AccessReview
Structure–Function Relationships of the Repeat Domains of RTX Toxins
Toxins 2019, 11(11), 657; https://doi.org/10.3390/toxins11110657 - 12 Nov 2019
Abstract
RTX proteins are a large family of polypeptides of mainly Gram-negative origin that are secreted into the extracellular medium by a type I secretion system featuring a non-cleavable C-terminal secretion signal, which is preceded by a variable number of nine-residue tandem repeats. The [...] Read more.
RTX proteins are a large family of polypeptides of mainly Gram-negative origin that are secreted into the extracellular medium by a type I secretion system featuring a non-cleavable C-terminal secretion signal, which is preceded by a variable number of nine-residue tandem repeats. The three-dimensional structure forms a parallel β-roll, where β-strands of two parallel sheets are connected by calcium-binding linkers in such a way that a right-handed spiral is built. The Ca2+ ions are an integral part of the structure, which cannot form without them. The structural determinants of this unique architecture will be reviewed with its conservations and variations together with the implication for secretion and folding of these proteins. The general purpose of the RTX domains appears to act as an internal chaperone that keeps the polypeptide unfolded in the calcium-deprived cytosol and triggers folding in the calcium-rich extracellular medium. A rather recent addition to the structural biology of the RTX toxin is a variant occurring in a large RTX adhesin, where this non-canonical β-roll binds to ice and diatoms. Full article
(This article belongs to the Special Issue RTX Toxins)
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Open AccessReview
The Biological Activity of Natural Alkaloids against Herbivores, Cancerous Cells and Pathogens
Toxins 2019, 11(11), 656; https://doi.org/10.3390/toxins11110656 - 11 Nov 2019
Abstract
The growing incidence of microorganisms that resist antimicrobials is a constant concern for the scientific community, while the development of new antimicrobials from new chemical entities has become more and more expensive, time-consuming, and exacerbated by emerging drug-resistant strains. In this regard, many [...] Read more.
The growing incidence of microorganisms that resist antimicrobials is a constant concern for the scientific community, while the development of new antimicrobials from new chemical entities has become more and more expensive, time-consuming, and exacerbated by emerging drug-resistant strains. In this regard, many scientists are conducting research on plants aiming to discover possible antimicrobial compounds. The secondary metabolites contained in plants are a source of chemical entities having pharmacological activities and intended to be used for the treatment of different diseases. These chemical entities have the potential to be used as an effective antioxidant, antimutagenic, anticarcinogenic and antimicrobial agents. Among these pharmacologically active entities are the alkaloids which are classified into a number of classes, including pyrrolizidines, pyrrolidines, quinolizidines, indoles, tropanes, piperidines, purines, imidazoles, and isoquinolines. Alkaloids that have antioxidant properties are capable of preventing a variety of degenerative diseases through capturing free radicals, or through binding to catalysts involved indifferent oxidation processes occurring within the human body. Furthermore, these entities are capable of inhibiting the activity of bacteria, fungi, protozoan and etc. The unique properties of these secondary metabolites are the main reason for their utilization by the pharmaceutical companies for the treatment of different diseases. Generally, these alkaloids are extracted from plants, animals and fungi. Penicillin is the most famous natural drug discovery deriving from fungus. Similarly, marines have been used as a source for thousands of bioactive marine natural products. In this review, we cover the medical use of natural alkaloids isolated from a variety of plants and utilized by humans as antibacterial, antiviral, antifungal and anticancer agents. An example for such alkaloids is berberine, an isoquinoline alkaloid, found in roots and stem-bark of Berberis asculin P. Renault plant and used to kill a variety of microorganisms. Full article
(This article belongs to the Special Issue Biological Activities of Alkaloids: From Toxicology to Pharmacology)
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Open AccessArticle
Porcine Hepatic Response to Fumonisin B1 in a Short Exposure Period: Fatty Acid Profile and Clinical Investigations
Toxins 2019, 11(11), 655; https://doi.org/10.3390/toxins11110655 - 10 Nov 2019
Abstract
Scarce studies have investigated the impact of fumonisin B1 (FB1) on the hepatic tissue fatty acid (FA) profile, and no study is available on piglets. A 10-day in vivo experiment was performed on seven piglets/group: control and FB1-fed [...] Read more.
Scarce studies have investigated the impact of fumonisin B1 (FB1) on the hepatic tissue fatty acid (FA) profile, and no study is available on piglets. A 10-day in vivo experiment was performed on seven piglets/group: control and FB1-fed animals (diet was contaminated with fungal culture: 20 mg FB1/kg diet). Independent sample t-test was carried out at p < 0.05 as the significance level. Neither growth, nor feed efficiency, was affected. The hepatic phospholipid (PL) fatty acids (FAs) were more susceptible for FB1, while triglyceride (TG) was less responsive. The impact of FB1 on hepatic PL polyunsaturated fatty acids (PUFAs) was more pronounced than on saturated fatty acids. Among all PUFAs, predominant ones in response were docosapentaenoicacid (DPA) (↓), docosahexaenoic DHA (↓) and arachidonic acids (↑). This led to a higher omega-6:omega-3 ratio, whereas a similar finding was noted in TGs. Neither total saturation (SFA) nor total monousaturation (MUFA) were affected by the FB1 administration. The liver showed an increase in malondialdehyde, as well as antioxidant capacity (reduced glutathione and glutathione peroxidase). The plasma enzymatic assessment revealed an increase in alkaline phosphatase (ALP), while alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), and gamma-glutamyltransferase (GGT) were not influenced. The microscopic sections provided evidence of vacuolar degeneration of the hepatocytes’ cytoplasm, but it was not severe. Furthermore, the lung edema was developed, while the kidney was not affected. In conclusion, regarding FB1-mediated hepatotoxicity in piglets, the potential effect of slight hepatotoxicity did not compromise growth performance, at least at the dose and exposure period applied. Full article
(This article belongs to the Special Issue Mycotoxin Exposure and Related Diseases)
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Open AccessArticle
Reduced Toxicity of Trichothecenes, Isotrichodermol, and Deoxynivalenol, by Transgenic Expression of the Tri101 3-O-Acetyltransferase Gene in Cultured Mammalian FM3A Cells
Toxins 2019, 11(11), 654; https://doi.org/10.3390/toxins11110654 - 10 Nov 2019
Abstract
In trichothecene-producing fusaria, isotrichodermol (ITDol) is the first intermediate with a trichothecene skeleton. In the biosynthetic pathway of trichothecene, a 3-O-acetyltransferase, encoded by Tri101, acetylates ITDol to a less-toxic intermediate, isotrichodermin (ITD). Although trichothecene resistance has been conferred to microbes [...] Read more.
In trichothecene-producing fusaria, isotrichodermol (ITDol) is the first intermediate with a trichothecene skeleton. In the biosynthetic pathway of trichothecene, a 3-O-acetyltransferase, encoded by Tri101, acetylates ITDol to a less-toxic intermediate, isotrichodermin (ITD). Although trichothecene resistance has been conferred to microbes and plants transformed with Tri101, there are no reports of resistance in cultured mammalian cells. In this study, we found that a 3-O-acetyl group of trichothecenes is liable to hydrolysis by esterases in fetal bovine serum and FM3A cells. We transfected the cells with Tri101 under the control of the MMTV-LTR promoter and obtained a cell line G3 with the highest level of C-3 acetylase activity. While the wild-type FM3A cells hardly grew in the medium containing 0.40 μM ITDol, many G3 cells survived at this concentration. The IC50 values of ITDol and ITD in G3 cells were 1.0 and 9.6 μM, respectively, which were higher than the values of 0.23 and 3.0 μM in the wild-type FM3A cells. A similar, but more modest, tendency was observed in deoxynivalenol and 3-acetyldeoxynivalenol. Our findings indicate that the expression of Tri101 conferred trichothecene resistance in cultured mammalian cells. Full article
(This article belongs to the Special Issue Toxicological Effects of Mycotoxin on Target Cells)
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Open AccessArticle
Dhb Microcystins Discovered in USA Using an Online Concentration LC–MS/MS Platform
Toxins 2019, 11(11), 653; https://doi.org/10.3390/toxins11110653 - 10 Nov 2019
Abstract
Based on current structural and statistical calculations, thousands of microcystins (MCs) can exist; yet, to date, only 246 MCs were identified and only 12 commercial MC standards are available. Standard mass spectrometry workflows for known and unknown MCs need to be developed and [...] Read more.
Based on current structural and statistical calculations, thousands of microcystins (MCs) can exist; yet, to date, only 246 MCs were identified and only 12 commercial MC standards are available. Standard mass spectrometry workflows for known and unknown MCs need to be developed and validated for basic and applied harmful algal bloom research to advance. Our investigation focuses on samples taken in the spring of 2018 from an impoundment fed by Oser and Bischoff Reservoirs, Indiana, United States of America (USA). The dominant cyanobacterium found during sampling was Planktothrix agardhii. The goal of our study was to identify and quantify the MCs in the impoundment sample using chemical derivatization and mass spectrometry. Modifying these techniques to use online concentration liquid chromatography tandem mass spectrometry (LC–MS/MS), two untargeted MCs have been identified, [d-Asp3, Dhb7]-MC-LR and [Dhb7]-MC-YR. [Dhb7]-MC-YR is not yet reported in the literature to date, and this was the first reported incidence of Dhb MCs in the United States. Furthermore, it was discovered that the commercially available [d-Asp3]-MC-RR standard was [d-Asp3, Dhb7]-MC-RR. This study highlights a workflow utilizing online concentration LC–MS/MS, high-resolution MS (HRMS), and chemical derivatization to identify isobaric MCs. Full article
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Open AccessArticle
Equol: A Microbiota Metabolite Able to Alleviate the Negative Effects of Zearalenone during In Vitro Culture of Ovine Preantral Follicles
Toxins 2019, 11(11), 652; https://doi.org/10.3390/toxins11110652 - 09 Nov 2019
Abstract
The impact of zearalenone (ZEN) on female reproduction remains an issue, since its effects may differ among exposed cell types. Besides the use of decontaminants in animal diet, other approaches should be considered to minimise ZEN effects after exposure. Since the first organ [...] Read more.
The impact of zearalenone (ZEN) on female reproduction remains an issue, since its effects may differ among exposed cell types. Besides the use of decontaminants in animal diet, other approaches should be considered to minimise ZEN effects after exposure. Since the first organ in contact with ZEN is the gastrointestinal tract, we hypothesise that products of microbiota metabolism may play a role in ZEN detoxification. We aimed to evaluate the effect of 1 µmol/L ZEN and 1 µmol/L equol (a microbial metabolite), alone or in combination, on the survival and morphology of in vitro cultured ovarian preantral follicles. Ovaries from 12 sheep were collected at a local abattoir and fragmented, and the ovarian pieces were submitted to in vitro culture for three days in the presence or absence of the test compounds. The follicular morphology was impaired by ZEN, but equol could alleviate the observed degeneration rates. While ZEN decreased cell proliferation in primary and secondary follicles, as well as induced DNA double-strand breaks in primordial follicles, all these observations disappeared when equol was added to a culture medium containing ZEN. In the present culture conditions, equol was able to counteract the negative effects of ZEN on ovarian preantral follicles. Full article
(This article belongs to the Section Mycotoxins)
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Open AccessArticle
The Effect of Botulinum Toxin Injections on Gross Motor Function for Lower Limb Spasticity in Children with Cerebral Palsy
Toxins 2019, 11(11), 651; https://doi.org/10.3390/toxins11110651 - 08 Nov 2019
Abstract
The aim of this study was to investigate the use of botulinum toxin type A (BoNT-A) injections and their efficacy on gross motor function for lower limb spasticity in children with spastic cerebral palsy (CP). This retrospective study included 919 injection occasions from [...] Read more.
The aim of this study was to investigate the use of botulinum toxin type A (BoNT-A) injections and their efficacy on gross motor function for lower limb spasticity in children with spastic cerebral palsy (CP). This retrospective study included 919 injection occasions from 591 children with CP who received a lower limb BoNT-A injection between 2006 and 2016. The Gross Motor Function Measure (GMFM-88), the Modified Ashworth Scale, and the Modified Tardieu Scale were administered before and after injections. Injections were predominantly administered to children under the age of 6 years. The most common muscle injection site was the calf muscle for dynamic foot deformity. The second most commonly injected muscle was the hip adductor among 2–3 year olds and the hamstring muscle among 4–6 year olds. Distal injections were predominantly administered to high-functioning children, whereas proximal injections were typically administered to low-functioning children. Multilevel injections were mostly administered to midfunctioning children. GMFM-88 scores significantly increased post-injection for both high- and low-functioning groups. Younger age at injection and distal injection type were associated with larger improvements on the GMFM-88 at both short- and midterm follow-up. The target muscles for injection varied depending on gross motor functioning and age. Younger age at injection and distal injection type were significantly related with greater gain in gross motor function. Full article
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Open AccessArticle
Uptake, Growth, and Pigment Changes in Lemna minor L. Exposed to Environmental Concentrations of Cylindrospermopsin
Toxins 2019, 11(11), 650; https://doi.org/10.3390/toxins11110650 - 07 Nov 2019
Abstract
Cylindrospermopsin (CYN)-producing cyanobacterial blooms such as Raphidiopsis, Aphanizomenon, Anabaena, Umezakia, and Lyngbya spp. are occurring more commonly and frequently worldwide. CYN is an environmentally stable extracellular toxin, which inhibits protein synthesis, and, therefore, can potentially affect a wide variety [...] Read more.
Cylindrospermopsin (CYN)-producing cyanobacterial blooms such as Raphidiopsis, Aphanizomenon, Anabaena, Umezakia, and Lyngbya spp. are occurring more commonly and frequently worldwide. CYN is an environmentally stable extracellular toxin, which inhibits protein synthesis, and, therefore, can potentially affect a wide variety of aquatic biota. Submerged and floating macrophytes, as primary producers in oligotrophic habitats, are at risk of exposure and information on the effects of CYN exposure at environmentally relevant concentrations is limited. In the present study, we investigated CYN uptake in the floating macrophyte Lemna minor with exposure to reported environmental concentrations. The effects were evaluated in terms of bioaccumulation, relative plant growth, and number of fronds per day. Variations in the concentrations and ratios of the chlorophylls as stress markers and carotenoids as markers of oxidative stress defense were measured. With exposure to 25 μg/L, L. minor could remove 43% of CYN within 24 h but CYN was not bioaccumulated. Generally, the pigment concentrations were elevated with exposure to 0.025, 0.25, and 2.5 μg/L CYN after 24 h, but normalized quickly thereafter. Changes in relative plant growth were observed with exposure to 0.25 and 2.5 μg/L CYN. Adverse effects were seen with these environmentally realistic concentrations within 24 h; however, L. minor successfully recovered within the next 48–96 h. Full article
Open AccessArticle
A Simple LC–MS Method for the Quantitation of Alkaloids in Endophyte-Infected Perennial Ryegrass
Toxins 2019, 11(11), 649; https://doi.org/10.3390/toxins11110649 - 07 Nov 2019
Abstract
The rapid identification and quantitation of alkaloids produced by Epichloë endophyte-infected pasture grass is important for the agricultural industry. Beneficial alkaloids, such as peramine, provide the grass with enhanced insect protection. Conversely, ergovaline and lolitrem B can negatively impact livestock. Currently, a single [...] Read more.
The rapid identification and quantitation of alkaloids produced by Epichloë endophyte-infected pasture grass is important for the agricultural industry. Beneficial alkaloids, such as peramine, provide the grass with enhanced insect protection. Conversely, ergovaline and lolitrem B can negatively impact livestock. Currently, a single validated method to measure these combined alkaloids in planta does not exist. Here, a simple two-step extraction method was developed for Epichloë-infected perennial ryegrass (Lolium perenne L.). Peramine, ergovaline and lolitrem B were quantified using liquid chromatography–mass spectrometry (LC–MS). Alkaloid linearity, limit of detection (LOD), limit of quantitation (LOQ), accuracy, precision, selectivity, recovery, matrix effect and robustness were all established. The validated method was applied to eight different ryegrass-endophyte symbiota. Robustness was established by comparing quantitation results across two additional instruments; a triple quadruple mass spectrometer (QQQ MS) and by fluorescence detection (FLD). Quantitation results were similar across all three instruments, indicating good reproducibility. LOQ values ranged from 0.8 ng/mL to 6 ng/mL, approximately one hundred times lower than those established by previous work using FLD (for ergovaline and lolitrem B), and LC–MS (for peramine). This work provides the first highly sensitive quantitative LC–MS method for the accurate and reproducible quantitation of important endophyte-derived alkaloids. Full article
(This article belongs to the Section Mycotoxins)
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Open AccessArticle
Crosstalk between Human Microvascular Endothelial Cells and Tubular Epithelial Cells Modulates Pro-Inflammatory Responses Induced by Shiga Toxin Type 2 and Subtilase Cytotoxin
Toxins 2019, 11(11), 648; https://doi.org/10.3390/toxins11110648 - 07 Nov 2019
Abstract
Hemolytic uremic syndrome (HUS) is a consequence of Shiga toxin (Stx)-producing Escherichia coli (STEC) infection and is the most frequent cause of acute renal failure (ARF) in children. Subtilase cytotoxin (SubAB) has also been associated with HUS pathogenesis. We previously reported that Stx2 [...] Read more.
Hemolytic uremic syndrome (HUS) is a consequence of Shiga toxin (Stx)-producing Escherichia coli (STEC) infection and is the most frequent cause of acute renal failure (ARF) in children. Subtilase cytotoxin (SubAB) has also been associated with HUS pathogenesis. We previously reported that Stx2 and SubAB cause different effects on co-cultures of human renal microvascular endothelial cells (HGEC) and human proximal tubular epithelial cells (HK-2) relative to HGEC and HK-2 monocultures. In this work we have analyzed the secretion of pro-inflammatory cytokines by co-cultures compared to monocultures exposed or not to Stx2, SubAB, and Stx2+SubAB. Under basal conditions, IL-6, IL-8 and TNF-α secretion was different between monocultures and co-cultures. After toxin treatments, high concentrations of Stx2 and SubAB decreased cytokine secretion by HGEC monocultures, but in contrast, low toxin concentrations increased their release. Toxins did not modulate the cytokine secretion by HK-2 monocultures, but increased their release in the HK-2 co-culture compartment. In addition, HK-2 monocultures were stimulated to release IL-8 after incubation with HGEC conditioned media. Finally, Stx2 and SubAB were detected in HGEC and HK-2 cells from the co-cultures. This work describes, for the first time, the inflammatory responses induced by Stx2 and SubAB, in a crosstalk model of renal endothelial and epithelial cells. Full article
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Open AccessReview
FGF23 and Phosphate–Cardiovascular Toxins in CKD
Toxins 2019, 11(11), 647; https://doi.org/10.3390/toxins11110647 - 06 Nov 2019
Abstract
Elevated levels of fibroblast growth factor 23 (FGF23) and phosphate are highly associated with increased cardiovascular disease and mortality in patients suffering from chronic kidney disease (CKD). As the kidney function declines, serum phosphate levels rise and subsequently induce the secretion of the [...] Read more.
Elevated levels of fibroblast growth factor 23 (FGF23) and phosphate are highly associated with increased cardiovascular disease and mortality in patients suffering from chronic kidney disease (CKD). As the kidney function declines, serum phosphate levels rise and subsequently induce the secretion of the phosphaturic hormone FGF23. In early stages of CKD, FGF23 prevents the increase of serum phosphate levels and thereby attenuates phosphate-induced vascular calcification, whereas in end-stage kidney disease, FGF23 fails to maintain phosphate homeostasis. Both hyperphosphatemia and elevated FGF23 levels promote the development of hypertension, vascular calcification, and left ventricular hypertrophy by distinct mechanisms. Therefore, FGF23 and phosphate are considered promising therapeutic targets to improve the cardiovascular outcome in CKD patients. Previous therapeutic strategies are based on dietary and pharmacological reduction of serum phosphate, and consequently FGF23 levels. However, clinical trials proving the effects on the cardiovascular outcome are lacking. Recent publications provide evidence for new promising therapeutic interventions, such as magnesium supplementation and direct targeting of phosphate and FGF receptors to prevent toxicity of FGF23 and hyperphosphatemia in CKD patients. Full article
(This article belongs to the Special Issue Uremia and Metabolic Complications of Chronic Kidney Disease )
Open AccessArticle
A Novel Niosome-Encapsulated Essential Oil Formulation to Prevent Aspergillus flavus Growth and Aflatoxin Contamination of Maize Grains During Storage
Toxins 2019, 11(11), 646; https://doi.org/10.3390/toxins11110646 - 06 Nov 2019
Abstract
Aflatoxin (AF) contamination of maize is a major concern for food safety. The use of chemical fungicides is controversial, and it is necessary to develop new effective methods to control Aspergillus flavus growth and, therefore, to avoid the presence of AFs in grains. [...] Read more.
Aflatoxin (AF) contamination of maize is a major concern for food safety. The use of chemical fungicides is controversial, and it is necessary to develop new effective methods to control Aspergillus flavus growth and, therefore, to avoid the presence of AFs in grains. In this work, we tested in vitro the effect of six essential oils (EOs) extracted from aromatic plants. We selected those from Satureja montana and Origanum virens because they show high levels of antifungal and antitoxigenic activity at low concentrations against A. flavus. EOs are highly volatile compounds and we have developed a new niosome-based encapsulation method to extend their shelf life and activity. These new formulations have been successfully applied to reduce fungal growth and AF accumulation in maize grains in a small-scale test, as well as placing the maize into polypropylene woven bags to simulate common storage conditions. In this latter case, the antifungal properties lasted up to 75 days after the first application. Full article
(This article belongs to the Special Issue Novel Approaches to Minimising Mycotoxin Contamination)
Open AccessArticle
Toxin Production in Soybean (Glycine max L.) Plants with Charcoal Rot Disease and by Macrophomina phaseolina, the Fungus that Causes the Disease
Toxins 2019, 11(11), 645; https://doi.org/10.3390/toxins11110645 - 06 Nov 2019
Cited by 1
Abstract
Charcoal rot disease, caused by the fungus Macrophomina phaseolina, results in major economic losses in soybean production in southern USA. M. phaseolina has been proposed to use the toxin (-)-botryodiplodin in its root infection mechanism to create a necrotic zone in root [...] Read more.
Charcoal rot disease, caused by the fungus Macrophomina phaseolina, results in major economic losses in soybean production in southern USA. M. phaseolina has been proposed to use the toxin (-)-botryodiplodin in its root infection mechanism to create a necrotic zone in root tissue through which fungal hyphae can readily enter the plant. The majority (51.4%) of M. phaseolina isolates from plants with charcoal rot disease produced a wide range of (-)-botryodiplodin concentrations in a culture medium (0.14–6.11 µg/mL), 37.8% produced traces below the limit of quantification (0.01 µg/mL), and 10.8% produced no detectable (-)-botryodiplodin. Some culture media with traces or no (-)-botryodiplodin were nevertheless strongly phytotoxic in soybean leaf disc cultures, consistent with the production of another unidentified toxin(s). Widely ranging (-)-botryodiplodin levels (traces to 3.14 µg/g) were also observed in the roots, but not in the aerial parts, of soybean plants naturally infected with charcoal rot disease. This is the first report of (-)-botryodiplodin in plant tissues naturally infected with charcoal rot disease. No phaseolinone was detected in M. phaseolina culture media or naturally infected soybean tissues. These results are consistent with (-)-botryodiplodin playing a role in the pathology of some, but not all, M. phaseolina isolates from soybeans with charcoal rot disease in southern USA. Full article
(This article belongs to the Special Issue Mycotoxins in Feed and Food Chain: Present Status and Future Concerns)
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Open AccessArticle
Deoxynivalenol Affects Proliferation and Expression of Activation-Related Molecules in Major Porcine T-Cell Subsets
Toxins 2019, 11(11), 644; https://doi.org/10.3390/toxins11110644 - 05 Nov 2019
Abstract
The Fusarium mycotoxin deoxynivalenol (DON) contaminates animal feed worldwide. In vivo, DON modifies the cellular protein synthesis, thereby also affecting the immune system. However, the functional consequences of this are still ill-defined. In this study, peripheral blood mononuclear cells from healthy pigs [...] Read more.
The Fusarium mycotoxin deoxynivalenol (DON) contaminates animal feed worldwide. In vivo, DON modifies the cellular protein synthesis, thereby also affecting the immune system. However, the functional consequences of this are still ill-defined. In this study, peripheral blood mononuclear cells from healthy pigs were incubated with different DON concentrations in the presence of Concanavalin A (ConA), a plant-derived polyclonal T-cell stimulant. T-cell subsets were investigated for proliferation and expression of CD8α, CD27, and CD28, which are involved in activation and costimulation of porcine T cells. A clear decrease in proliferation of all ConA-stimulated major T-cell subsets (CD4+, CD8+, and γδ T cells) was observed in DON concentrations higher than 0.4 µM. This applied in particular to naïve CD4+ and CD8+ T cells. From 0.8 μM onwards, DON induced a reduction of CD8α (CD4+) and CD27 expression (CD4+ and CD8+ T cells). CD28 expression was diminished in CD4+ and CD8+ T cells at a concentration of 1.6 µM DON. None of these effects were observed with the DON-derivative deepoxy-deoxynivalenol (DOM-1) at 16 µM. These results indicate that DON reduces T-cell proliferation and the expression of molecules involved in T-cell activation, providing a molecular basis for some of the described immunosuppressive effects of DON. Full article
(This article belongs to the Section Mycotoxins)
Open AccessReview
A Review of the Effect of Trace Metals on Freshwater Cyanobacterial Growth and Toxin Production
Toxins 2019, 11(11), 643; https://doi.org/10.3390/toxins11110643 - 05 Nov 2019
Abstract
Cyanobacterial blooms are becoming more common in freshwater systems, causing ecological degradation and human health risks through exposure to cyanotoxins. The role of phosphorus and nitrogen in cyanobacterial bloom formation is well documented and these are regularly the focus of management plans. There [...] Read more.
Cyanobacterial blooms are becoming more common in freshwater systems, causing ecological degradation and human health risks through exposure to cyanotoxins. The role of phosphorus and nitrogen in cyanobacterial bloom formation is well documented and these are regularly the focus of management plans. There is also strong evidence that trace metals are required for a wide range of cellular processes, however their importance as a limiting factor of cyanobacterial growth in ecological systems is unclear. Furthermore, some studies have suggested a direct link between cyanotoxin production and some trace metals. This review synthesises current knowledge on the following: (1) the biochemical role of trace metals (particularly iron, cobalt, copper, manganese, molybdenum and zinc), (2) the growth limitation of cyanobacteria by trace metals, (3) the trace metal regulation of the phytoplankton community structure and (4) the role of trace metals in cyanotoxin production. Iron dominated the literature and regularly influenced bloom formation, with 15 of 18 studies indicating limitation or colimitation of cyanobacterial growth. A range of other trace metals were found to have a demonstrated capacity to limit cyanobacterial growth, and these metals require further study. The effect of trace metals on cyanotoxin production is equivocal and highly variable. Better understanding the role of trace metals in cyanobacterial growth and bloom formation is an essential component of freshwater management and a direction for future research. Full article
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Open AccessArticle
Investigation of the In-Vivo Cytotoxicity and the In Silico-Prediction of MDM2-p53 Inhibitor Potential of Euphorbia peplus Methanolic Extract in Rats
Toxins 2019, 11(11), 642; https://doi.org/10.3390/toxins11110642 - 04 Nov 2019
Abstract
This study explored the probable in vivo cardiac and renal toxicities together with in silico approaches for predicting the apoptogenic potential of Euphorbia peplus methanolic extract (EPME) in rats. Cardiac and renal injury biomarkers were estimated with histopathological and immunohistochemical evaluations of both [...] Read more.
This study explored the probable in vivo cardiac and renal toxicities together with in silico approaches for predicting the apoptogenic potential of Euphorbia peplus methanolic extract (EPME) in rats. Cardiac and renal injury biomarkers were estimated with histopathological and immunohistochemical evaluations of both kidney and heart. The probable underlying mechanism of E. peplus compounds to potentiate p53 activity is examined using Molecular Operating Environment (MOE) docking software and validated experimentally by immunohistochemical localization of p53 protein in the kidney and heart tissues. The gas chromatography/mass spectrometry analysis of E. peplus revealed the presence of nine different compounds dominated by di-(2-ethylhexyl) phthalate (DEHP). Significant elevations of troponin, creatine phosphokinase, creatine kinase–myocardium bound, lactate dehydrogenase, aspartate transaminase, alkaline phosphatase, urea, creatinine, and uric acid were evident in the EPME treated rats. The EPME treated rats showed strong renal and cardiac p53 expression and moderate cardiac TNF-α expression. Further, our in silico results predicted the higher affinity and good inhibition of DEHP, glyceryl linolenate, and lucenin 2 to the MDM2-p53 interface compared to the standard reference 15 a compound. Conclusively, EPME long-term exposure could adversely affect the cardiac and renal tissues probably due to their inflammatory and apoptotic activity. Moreover, the in silico study hypothesizes that EPME inhibits MDM2-mediated degradation of p53 suggesting possible anticancer potentials which confirmed experimental by strong p53 expression in renal and cardiac tissues. Full article
(This article belongs to the collection Toxic and Pharmacological Effect of Plant Toxins)
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Open AccessReview
Using Botulinum Toxin A for Treatment of Interstitial Cystitis/Bladder Pain Syndrome—Possible Pathomechanisms and Practical Issues
Toxins 2019, 11(11), 641; https://doi.org/10.3390/toxins11110641 - 04 Nov 2019
Abstract
Treatment for patients with interstitial cystitis/bladder pain syndrome (IC/BPS) is always challenging for urologists. The main mechanism of the botulinum toxin A (BoNT-A) is inhibition of muscle contraction, but the indirect sensory modulation and anti-inflammatory effect in the bladder also play important roles [...] Read more.
Treatment for patients with interstitial cystitis/bladder pain syndrome (IC/BPS) is always challenging for urologists. The main mechanism of the botulinum toxin A (BoNT-A) is inhibition of muscle contraction, but the indirect sensory modulation and anti-inflammatory effect in the bladder also play important roles in treating patients with IC/BPS. Although current guidelines consider BoNT-A injection to be a standard treatment, some practical issues remain debatable. Most clinical evidence of this treatment comes from retrospective uncontrolled studies, and only two randomized placebo-control studies with limited patient numbers have been published. Although 100 U BoNT-A is effective for most patients with IC/BPS, the potential efficacy of 200 U BoNT-A has not been evaluated. Both trigone and diffuse body BoNT-A injections are effective and safe for IC/BPS, although comparison studies are lacking. For IC/BPS patients with Hunner’s lesion, the efficacy of BoNT-A injection remains controversial. Most patients with IC/BPS experience symptomatic relapse at six to nine months after a BoNT-A injection, although repeated injections exhibit a persistent therapeutic effect in long-term follow-up. Further randomized placebo-controlled studies with a larger number of patients are needed to support BoNT-A as standard treatment for patients with IC/BPS. Full article
Open AccessReview
Co-Occurrence and Combinatory Effects of Alternaria Mycotoxins and other Xenobiotics of Food Origin: Current Scenario and Future Perspectives
Toxins 2019, 11(11), 640; https://doi.org/10.3390/toxins11110640 - 03 Nov 2019
Abstract
Mycotoxins are low-molecular weight compounds produced by diverse genera of molds that may contaminate food and feed threatening the health of humans and animals. Recent findings underline the importance of studying the combined occurrence of multiple mycotoxins and the relevance of assessing the [...] Read more.
Mycotoxins are low-molecular weight compounds produced by diverse genera of molds that may contaminate food and feed threatening the health of humans and animals. Recent findings underline the importance of studying the combined occurrence of multiple mycotoxins and the relevance of assessing the toxicity their simultaneous exposure may cause in living organisms. In this context, for the first time, this work has critically reviewed the most relevant data concerning the occurrence and toxicity of mycotoxins produced by Alternaria spp., which are among the most important emerging risks to be assessed in food safety, alone or in combination with other mycotoxins and bioactive food constituents. According to the literature covered, multiple Alternaria mycotoxins may often occur simultaneously in contaminated food, along with several other mycotoxins and food bioactives inherently present in the studied matrices. Although the toxicity of combinations naturally found in food has been rarely assessed experimentally, the data collected so far, clearly point out that chemical mixtures may differ in their toxicity compared to the effect of toxins tested individually. The data presented here may provide a solid foothold to better support the risk assessment of Alternaria mycotoxins highlighting the actual role of chemical mixtures on influencing their toxicity. Full article
(This article belongs to the Special Issue Mycotoxins in Feed and Food Chain: Present Status and Future Concerns)
Open AccessArticle
Cytotoxicity of Deoxynivalenol after Being Exposed to Gaseous Ozone
Toxins 2019, 11(11), 639; https://doi.org/10.3390/toxins11110639 - 02 Nov 2019
Abstract
In this study, deoxynivalenol (DON) in aqueous solution was exposed to gaseous ozone for periods ranging from 0 to 20 min. The degradation efficiency and cytotoxicity of DON were investigated after being treated by ozone. The results showed that DON was rapidly degraded [...] Read more.
In this study, deoxynivalenol (DON) in aqueous solution was exposed to gaseous ozone for periods ranging from 0 to 20 min. The degradation efficiency and cytotoxicity of DON were investigated after being treated by ozone. The results showed that DON was rapidly degraded from 10.76 ± 0.09 mg/L to 0.22 ± 0.04 mg/L within 15 min (P < 0.05), representing a reduction of 97.95%, and no DON was detected after being exposed to 14.50 mg/L of ozone at a flow rate of 80 mL/min for 20 min. The degradation of DON depended on the ozone exposure time, and followed the first-order kinetic model (R2 = 0.9972). Human hepatic carcinoma (HepG2) and Henrietta Lacks (Hela) cells were used to evaluate the cytotoxicity of DON treated by ozone using the 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The half-maximal inhibitory concentrations (IC50) values of DON on HepG2 and Hela cells were 2.10 and 1.33 mg/L after 48 h of exposure, respectively, and showed a dose-dependent manner. The cell vitalities of HepG2 and Hela cells on DON were both evidently improved after being exposed to ozone for 15 min, and there were no significant differences between the negative control and that treated at 20 min of ozone exposure. Gaseous ozone can potentially be used as a new method to detoxify DON in agricultural products. Full article
(This article belongs to the Section Mycotoxins)
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Open AccessArticle
Total Dietary Intake and Health Risks Associated with Exposure to Aflatoxin B1, Ochratoxin A and Fuminisins of Children in Lao Cai Province, Vietnam
Toxins 2019, 11(11), 638; https://doi.org/10.3390/toxins11110638 - 02 Nov 2019
Abstract
The health burden of foodborne mycotoxins is considerable, but particularly for children due to their lower detoxification capacity, rapid growth and high intake of food in proportion to their weight. Through a Total Dietary Study approach, the objective was to estimate the dietary [...] Read more.
The health burden of foodborne mycotoxins is considerable, but particularly for children due to their lower detoxification capacity, rapid growth and high intake of food in proportion to their weight. Through a Total Dietary Study approach, the objective was to estimate the dietary exposure and health risk caused by mycotoxins for children under 5 years living in the Lao Cai province in northern Vietnam. A total of 40 composite food samples representing 1008 individual food samples were processed and analyzed by ELISA for aflatoxin B1, ochratoxin A and fumonisins. Results showed that dietary exposure to aflatoxin B1, ochratoxin A and total fumonisins were 118.7 ng/kgbw/day, 52.6 ng/kg bw/day and 1250.0 ng/kg bw/day, respectively. Using a prevalence of hepatitis of 1%, the risk of liver cancer related to exposure of aflatoxin B1 was 12.1 cases/100,000 individual/year. Age-adjusted margin of exposure (MOE) of renal cancer associated with ochratoxin A was 127, while MOE of liver cancer associated with fumonisins was 542. Antropometric data show that 50.4% (60/119) of children were stunted, i.e. height/length for age z-scores (HAZ) below –2, and 3.4% (4/119) of children were classified as wasted, i.e. weight for height z-scores (WHZ) below –2. A significant negative relationship between dietary exposure to individual or mixture of mycotoxins and growth of children was observed indicating that the high mycotoxin intake contributed to stunning in the children studied. Full article
(This article belongs to the Special Issue Mycotoxin Exposure and Related Diseases)
Open AccessArticle
Hadrurid Scorpion Toxins: Evolutionary Conservation and Selective Pressures
Toxins 2019, 11(11), 637; https://doi.org/10.3390/toxins11110637 - 01 Nov 2019
Abstract
Scorpion toxins are thought to have originated from ancestral housekeeping genes that underwent diversification and neofunctionalization, as a result of positive selection. Our understanding of the evolutionary origin of these peptides is hindered by the patchiness of existing taxonomic sampling. While recent studies [...] Read more.
Scorpion toxins are thought to have originated from ancestral housekeeping genes that underwent diversification and neofunctionalization, as a result of positive selection. Our understanding of the evolutionary origin of these peptides is hindered by the patchiness of existing taxonomic sampling. While recent studies have shown phylogenetic inertia in some scorpion toxins at higher systematic levels, evolutionary dynamics of toxins among closely related taxa remain unexplored. In this study, we used new and previously published transcriptomic resources to assess evolutionary relationships of closely related scorpions from the family Hadruridae and their toxins. In addition, we surveyed the incidence of scorpine-like peptides (SLP, a type of potassium channel toxin), which were previously known from 21 scorpion species. We demonstrate that scorpine-like peptides exhibit gene duplications. Our molecular analyses demonstrate that only eight sites of two SLP copies found in scorpions are evolving under positive selection, with more sites evolving under negative selection, in contrast to previous findings. These results show evolutionary conservation in toxin diversity at shallow taxonomic scale. Full article
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Open AccessArticle
Morphological and Transcriptomic Analysis of the Inhibitory Effects of Lactobacillus plantarum on Aspergillus flavus Growth and Aflatoxin Production
Toxins 2019, 11(11), 636; https://doi.org/10.3390/toxins11110636 - 01 Nov 2019
Abstract
Lactobacillus plantarum, as a natural bio-preservative, has attracted a great deal of attention in recent years. In this study, 22 L. plantarum strains were tested against the aflatoxin-producing fungus, Aspergillus flavus; strain IAMU80070 showed the highest antifungal activity. At a [...] Read more.
Lactobacillus plantarum, as a natural bio-preservative, has attracted a great deal of attention in recent years. In this study, 22 L. plantarum strains were tested against the aflatoxin-producing fungus, Aspergillus flavus; strain IAMU80070 showed the highest antifungal activity. At a concentration of 5 × 105 colony-forming units (CFU) mL−1, it completely inhibited A. flavus growth and decreased aflatoxin production by 93%. Furthermore, ultrastructural examination showed that IAMU80070 destroyed the cellular structure of hyphae and spores. To explore the inhibitory effect of IAMU80070 on A. flavus at the transcriptional level, transcriptome data were obtained and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The aflatoxin biosynthetic process was the most significantly downregulated functional category, while genes implicated in the synthesis and organization of cell wall polysaccharides were upregulated. Quantitative real-time PCR results verified the credibility and reliability of the RNA sequencing data. These results provided insight into the transcriptome of A. flavus in response to the antagonistic effects of L. plantarum IAMU80070. Full article
Open AccessArticle
Elevation of Trimethylamine-N-Oxide in Chronic Kidney Disease: Contribution of Decreased Glomerular Filtration Rate
Toxins 2019, 11(11), 635; https://doi.org/10.3390/toxins11110635 - 01 Nov 2019
Abstract
Gut microbiota-dependent Trimethylamine-N-oxide (TMAO) has been reported to be strongly linked to renal function and to increased cardiovascular events in the general population and in Chronic Kidney Disease (CKD) patients. Considering the lack of data assessing renal handling of TMAO, we conducted this [...] Read more.
Gut microbiota-dependent Trimethylamine-N-oxide (TMAO) has been reported to be strongly linked to renal function and to increased cardiovascular events in the general population and in Chronic Kidney Disease (CKD) patients. Considering the lack of data assessing renal handling of TMAO, we conducted this study to explore renal excretion and mechanisms of accumulation of TMAO during CKD. We prospectively measured glomerular filtration rate (mGFR) with gold standard methods and plasma concentrations of trimethylamine (TMA), TMAO, choline, betaine, and carnitine by LC-MS/MS in 124 controls, CKD, and hemodialysis (HD) patients. Renal clearance of each metabolite was assessed in a sub-group of 32 patients. Plasma TMAO was inversely correlated with mGFR (r2 = 0.388, p < 0.001), confirming elevation of TMAO plasma levels in CKD. TMAO clearances were not significantly different from mGFR, with a mean ± SD TMAO fractional excretion of 105% ± 32%. This suggests a complete renal excretion of TMAO by glomerular filtration with a negligible participation of tubular secretion or reabsorption, during all stages of CKD. Moreover, TMAO was effectively removed within 4 h of hemodiafiltration, showing a higher fractional reduction value than that of urea (84.9% ± 6.5% vs. 79.2% ± 5.7%, p = 0.04). This study reports a strong correlation between plasma TMAO levels and mGFR, in CKD, that can be mainly related to a decrease in TMAO glomerular filtration. Clearance data did not support a significant role for tubular secretion in TMAO renal elimination. Full article
(This article belongs to the Section Uremic Toxins)
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Open AccessReview
Trichothecenes in Cereal Grains – An Update
Toxins 2019, 11(11), 634; https://doi.org/10.3390/toxins11110634 - 31 Oct 2019
Abstract
Trichothecenes are sesquiterpenoid mycotoxins produced by fungi from the order Hypocreales, including members of the Fusarium genus that infect cereal grain crops. Different trichothecene-producing Fusarium species and strains have different trichothecene chemotypes belonging to the Type A and B class. These fungi cause [...] Read more.
Trichothecenes are sesquiterpenoid mycotoxins produced by fungi from the order Hypocreales, including members of the Fusarium genus that infect cereal grain crops. Different trichothecene-producing Fusarium species and strains have different trichothecene chemotypes belonging to the Type A and B class. These fungi cause a disease of small grain cereals, called Fusarium head blight, and their toxins contaminate host tissues. As potent inhibitors of eukaryotic protein synthesis, trichothecenes pose a health risk to human and animal consumers of infected cereal grains. In 2009, Foroud and Eudes published a review of trichothecenes in cereal grains for human consumption. As an update to this review, the work herein provides a comprehensive and multi-disciplinary review of the Fusarium trichothecenes covering topics in chemistry and biochemistry, pathogen biology, trichothecene toxicity, molecular mechanisms of resistance or detoxification, genetics of resistance and breeding strategies to reduce their contamination of wheat and barley. Full article
(This article belongs to the Special Issue Mycotoxigenic Fungi and Their Interactions with Plants)
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Open AccessArticle
Efficacy of a Yeast Cell Wall Extract to Mitigate the Effect of Naturally Co-Occurring Mycotoxins Contaminating Feed Ingredients Fed to Young Pigs: Impact on Gut Health, Microbiome, and Growth
Toxins 2019, 11(11), 633; https://doi.org/10.3390/toxins11110633 - 31 Oct 2019
Abstract
Mycotoxins are produced by fungi and are potentially toxic to pigs. Yeast cell wall extract (YCWE) is known to adsorb mycotoxins and improve gut health in pigs. One hundred and twenty growing (56 kg; experiment 1) and 48 nursery piglets (6 kg; experiment [...] Read more.
Mycotoxins are produced by fungi and are potentially toxic to pigs. Yeast cell wall extract (YCWE) is known to adsorb mycotoxins and improve gut health in pigs. One hundred and twenty growing (56 kg; experiment 1) and 48 nursery piglets (6 kg; experiment 2) were assigned to four dietary treatments in a 2 × 2 factorial design for 35 and 48 days, respectively. Factors were mycotoxins (no addition versus experiment 1: 180 μg/kg aflatoxins and 14 mg/kg fumonisins; or experiment 2: 180 μg/kg aflatoxins and 9 mg/kg fumonisins, and 1 mg/kg deoxynivalenol) and YCWE (0% versus 0.2%). Growth performance, blood, gut health and microbiome, and apparent ileal digestibility (AID) data were evaluated. In experiment 1, mycotoxins reduced ADG and G:F, and duodenal IgG, whereas in jejunum, YCWE increased IgG and reduced villus width. In experiment 2, mycotoxins reduced BW, ADG, and ADFI. Mycotoxins reduced ADG, which was recovered by YCWE. Mycotoxins reduced the AID of nutrients evaluated and increased protein carbonyl, whereas mycotoxins and YCWE increased the AID of the nutrients and reduced protein carbonyl. Mycotoxins reduced villus height, proportion of Ki-67-positive cells, and increased IgA and the proportion of bacteria with mycotoxin-degrading ability, whereas YCWE tended to increase villus height and reduced IgA and the proportion of pathogenic bacteria in jejunum. The YCWE effects were more evident in promoting gut health and growth in nursery pigs, which showed higher susceptibility to mycotoxin effects. Full article
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Open AccessArticle
Improved Accuracy of Saxitoxin Measurement Using an Optimized Enzyme-Linked Immunosorbent Assay
Toxins 2019, 11(11), 632; https://doi.org/10.3390/toxins11110632 - 31 Oct 2019
Abstract
Paralytic shellfish poisoning (PSP) is precipitated by a family of toxins produced by harmful algae, which are consumed by filter-feeding and commercially popular shellfish. The toxins, including saxitoxin, neosaxitoxin, and gonyautoxins, accumulate in shellfish and cause intoxication when consumed by humans and animals. [...] Read more.
Paralytic shellfish poisoning (PSP) is precipitated by a family of toxins produced by harmful algae, which are consumed by filter-feeding and commercially popular shellfish. The toxins, including saxitoxin, neosaxitoxin, and gonyautoxins, accumulate in shellfish and cause intoxication when consumed by humans and animals. Symptoms can range from minor neurological dysfunction to respiratory distress and death. There are over 40 different chemical congeners of saxitoxin and its analogs, many of which are toxic and many of which have low toxicity or are non-toxic. This makes accurate toxicity assessment difficult and complicates decisions regarding whether or not shellfish are safe to consume. In this study, we describe a new antibody-based bioassay that is able to detect toxic congeners (saxitoxin, neosaxitoxin, and gonyautoxins) with little cross-reactivity with the low or non-toxic congeners (decarbamoylated or di-sulfated forms). The anti-saxitoxin antibody used in this assay detects saxitoxin and neosaxitoxin, the two most toxic congers equally well, but not the relatively highly toxic gonyautoxins. By incorporating an incubation step with L-cysteine, it is possible to convert a majority of the gonyautoxins present to saxitoxin and neosaxitoxin, which are readily detected. The assay is, therefore, capable of detecting the most toxic PSP congeners found in commercially relevant shellfish. The assay was validated against samples whose toxicity was determined using standard HPLC methods and yielded a strong linear agreement between the methods, with R2 values of 0.94–0.96. As ELISAs are rapid, inexpensive, and easy-to-use, this new commercially available PSP ELISA represents an advance in technology allowing better safety management of the seafood supply and the ability to screen large numbers of samples that can occur when monitoring is increased substantially in response to toxic bloom events Full article
(This article belongs to the Special Issue Marine Toxins Detection)
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Open AccessArticle
Calm Before the Storm: A Glimpse into the Secondary Metabolism of Aspergillus welwitschiae, the Etiologic Agent of the Sisal Bole Rot
Toxins 2019, 11(11), 631; https://doi.org/10.3390/toxins11110631 - 30 Oct 2019
Abstract
Aspergillus welwitschiae is a species of the Nigri section of the genus Aspergillus. In nature, it is usually a saprotroph, decomposing plant material. However, it causes the bole rot disease of Agave sisalana (sisal), a plant species used for the extraction of [...] Read more.
Aspergillus welwitschiae is a species of the Nigri section of the genus Aspergillus. In nature, it is usually a saprotroph, decomposing plant material. However, it causes the bole rot disease of Agave sisalana (sisal), a plant species used for the extraction of hard natural fibers, causing great economic loss to this culture. In this study, we isolated and sequenced one genome of A. welwitschiae (isolate CCMB 674 (Collection of Cultures of Microorganisms of Bahia)) from the stem tissues of sisal and performed in silico and wet lab experimental strategies to describe its ability to produce mycotoxins. CCMB 674 possesses 64 secondary metabolite gene clusters (SMGCs) and, under normal conditions, it produces secondary metabolism compounds that could disturb the cellular cycle of sisal or induce abnormalities in plant growth, such as malformin C. This isolate also produces a pigment that might explain the characteristic red color of the affected tissues. Additionally, this isolate is defective for the production of fumonisin B1, and, despite bearing the full cluster for the synthesis of this compound, it did not produce ochratoxin A. Altogether, these results provide new information on possible strategies used by the fungi during the sisal bole rot, helping to better understand this disease and how to control it. Full article
(This article belongs to the Special Issue Mycotoxins: Producing Fungi and Mechanisms of Phytotoxicity)
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