Edodin: A New Type of Toxin from Shiitake Mushroom (Lentinula edodes) That Inactivates Mammalian Ribosomes.

Ribosome-inactivating proteins (RIPs) are a group of proteins with rRNA N-glycosylase activity that irreversibly inhibit protein synthesis and consequently cause cell death. Recently, an RIP called ledodin has been found in shiitake; it is cytotoxic, strongly inhibits protein synthesis, and shows rRNA N-glycosylase activity. In this work, we isolated and characterized a 50 kDa cytotoxic protein from shiitake that we named edodin. Edodin inhibits protein synthesis in a mammalian cell-free system, but not in insect-, yeast-, and bacteria-derived systems. It exhibits rRNA N-glycosylase and DNA-nicking activities, which relate it to plant RIPs. It was also shown to be toxic to HeLa and COLO 320 cells. Its structure is not related to other RIPs found in plants, bacteria, or fungi, but, instead, it presents the characteristic structure of the fold type I of pyridoxal phosphate-dependent enzymes. Homologous sequences have been found in other fungi of the class Agaricomycetes; thus, edodin could be a new type of toxin present in many fungi, some of them edible, which makes them of great interest in health, both for their involvement in food safety and for their potential biomedical and biotechnological applications.

The Effect of Combined Exposure of Fusarium Mycotoxins on Lipid Peroxidation, Antioxidant Defense, Fatty Acid Profile, and Histopathology in Laying Hens' Liver.

Fumonisin B1, T-2 toxin, and deoxynivalenol are frequently detected in feed materials. The mycotoxins induce free radical formation and, thereby, lipid peroxidation. The effects of mycotoxin exposure at the EU recommended limit (T-2/HT-2 toxin: 0.25 mg/kg; DON = 3AcDON/15-AScDON: 5 mg/kg; fumonisin B1: 20 mg/kg) and double dose (T-2/HT-2 toxin: 0.5 mg/kg, DON/3-AcDON/15-AcDON: 10 mg, and FB1: 40 mg/kg feed) were investigated during short-term (3 days) per os exposure in the liver of laying hens. On day 1 higher while on day 3 lower MDA concentrations were found in the low-dose group compared to the control. Fatty acid composition also changed: the proportion of monounsaturated fatty acids increased (p < 0.05) and the proportion of polyunsaturated fatty acids decreased by day 3. These alterations resulted in a decrease in the index of unsaturation and average fatty acid chain length. Histopathological alterations suggested that the incidence and severity of liver lesions were higher in the mycotoxin-treated laying hens, and the symptoms correlated with the fatty acid profile of total phospholipids. Overall, the findings revealed that mycotoxin exposure, even at the EU-recommended limits, induced lipid peroxidation in the liver, which led to changes in fatty acid composition, matched with tissue damage.

Evaluating the human neurotoxicity and toxicological interactions impact of co-occurring regulated and emerging mycotoxins.

Mycotoxins can inflict harmful effects on diverse organs, and mounting evidence indicates their potential involvement in human neurodegenerative diseases. Given the common occurrence of these toxins in food, there is an increasing demand for a comprehensive assessment of their combined toxicity to enhance our understanding of their potential hazards. This research investigates mycotoxin exposure from widely consumed cereal-based products, including enniatin B (ENNB), sterigmatocystin (STG), aflatoxin B1 (AFB1), cyclopiazonic acid (CPZ), citrinin (CIT), and ochratoxin A (OTA). Employing the median-effect equation based on Chou and Talalay's mass-action law, we assessed their cytotoxicity in human SH-SY5Y neuronal cells. Notably, ENNB displayed the highest neurotoxicity (IC50 = 3.72 µM), followed by OTA (9.10 µM) and STG (9.99 µM). The combination of OTA + STG exhibited the highest toxicity (IC50 = 3.77 µM), while CPZ + CIT showed the least detrimental effect. Approximately 70 % of tested binary combinations displayed synergistic or additive effects, except for ENNB + STG, ENNB + AFB1, and CPZ + CIT, which showed antagonistic interactions. Intriguingly, the senary combination displayed moderate antagonism at the lowest exposure and moderate synergism at higher doses. OTA exhibited predominantly synergistic interactions, comprising approximately 90 %, a noteworthy finding considering its prevalence in food. Conversely, ENNB interactions tended to be antagonistic. The most remarkable synergy occurred in the STG and CIT combination, enabling a 50-fold reduction in CIT dosage for an equivalent toxic effect. These findings highlight the biological relevance of robust synergistic interactions, emphasizing the need to assess human exposure hazards accurately, particularly considering frequent mycotoxin co-occurrence in environmental and food settings.

PI3K/Akt/FoxO Pathway Mediates Antagonistic Toxicity in HepG2 Cells Coexposed to Deoxynivalenol and Enniatins.

The emerging mycotoxins enniatins (ENNs) and the traditional mycotoxin deoxynivalenol (DON) often co-contaminate various grain raw materials and foods. While the liver is their common target organ, the mechanism of their combined effect remains unclear. In this study, the combined cytotoxic effects of four ENNs (ENA, ENA1, ENB, and ENB1) with DON and their mechanisms were investigated using the HepG2 cell line. Additionally, a population exposure risk assessment of these mycotoxins was performed by using in vitro experiments and computer simulations. The results showed that only ENA at 1/4 IC50 and ENB1 at 1/8 IC50 coexposed with DON showed an additive effect, while ENB showed the strongest antagonism at IC50 (CI = 3.890). Co-incubation of ENNs regulated the signaling molecule levels which were disrupted by DON. Transcriptome analysis showed that ENB (IC50) up-regulated the PI3K/Akt/FoxO signaling pathway and inhibited the expression of apoptotic genes (Bax, P53, Caspase 3, etc.) via phosphorylation of FoxO, thereby reducing the cytotoxic effects caused by DON. Both types of mycotoxins posed serious health risks, and the cumulative risk of coexposure was particularly important for emerging mycotoxins.

Natural compounds mitigate mycotoxins-induced neurotoxicity by modulating oxidative tonus: in vitro and in vivo insights - a review.

This review explores the repercussions of mycotoxin contamination in food and feed, emphasising potential threats to agriculture, animal husbandry and public health. The primary objective is to make a comprehensive assessment of the neurotoxic consequences of mycotoxin exposure, an aspect less explored in current literature. Emphasis is placed on prominent mycotoxins, including aflatoxins, fumonisins, zearalenone (ZEA) and ochratoxins, known for inducing acute and chronic diseases such as liver damage, genetic mutation and cancer. To elucidate the effects, animal studies were conducted, revealing an association between mycotoxin exposure and neurological damage. This encompasses impairments in learning and memory, motor alterations, anxiety and depression. The underlying mechanisms involve oxidative stress, disrupting the balance between reactive oxygen species (ROS) and antioxidant capacity. This oxidative stress is linked to neuronal damage, brain inflammation, neurochemical imbalance, and subsequent behavioural changes. The review underscores the need for preventive measures against mycotoxin exposure. While complete avoidance is ideal, exploration into the potential use of antioxidants as a viable solution is discussed, given the widespread contamination of many food products. Specifically, the protective role of natural compounds, such as polyphenols, is highlighted, showcasing their efficacy in mitigating mycotoxicosis in the central nervous system (CNS), as evidenced by findings in various animal models. In summary, countering mycotoxin-induced neurotoxicity requires a multifaceted approach. The identified natural compounds show promise, but their practical use hinges on factors like bioavailability, toxicity and understanding their mechanisms of action. Extensive research is crucial, considering the diverse responses to different mycotoxins and neurological conditions. Successful implementation relies on factors such as the specific mycotoxin(s) involved and achievable effective concentrations. Further research and clinical trials are imperative to establish the safety and efficacy of these compounds in practical applications.

Effect of Acrylamide and Mycotoxins in SH-SY5Y Cells: A Review.

Thermal processes induce the formation of undesired toxic components, such as acrylamide (AA), which has been shown to induce brain toxicity in humans and classified as Group 2A by the International Agency of Research in Cancer (IARC), as well as some mycotoxins. AA and mycotoxins' toxicity is studied in several in vitro models, including the neuroblastoma cell line model SH-SY5Y cells. Both AA and mycotoxins occur together in the same food matrix cereal base (bread, pasta, potatoes, coffee roasting, etc.). Therefore, the goal of this review is to deepen the knowledge about the neurological effects that AA and mycotoxins can induce on the in vitro model SH-SY5Y and its mechanism of action (MoA) focusing on the experimental assays reported in publications of the last 10 years. The analysis of the latest publications shows that most of them are focused on cytotoxicity, apoptosis, and alteration in protein expression, while others are interested in oxidative stress, axonopathy, and the disruption of neurite outgrowth. While both AA and mycotoxins have been studied in SH-SY5Y cells separately, the mixture of them is starting to draw the interest of the scientific community. This highlights a new and interesting field to explore due to the findings reported in several publications that can be compared and the implications in human health that both could cause. In relation to the assays used, the most employed were the MTT, axonopathy, and qPCR assays. The concentration dose range studied was 0.1-10 mM for AA and 2 fM to 200 µM depending on the toxicity and time of exposure for mycotoxins. A healthy and varied diet allows the incorporation of a large family of bioactive compounds that can mitigate the toxic effects associated with contaminants present in food. Although this has been reported in some publications for mycotoxins, there is still a big gap for AA which evidences that more investigations are needed to better explore the risks for human health when exposed to AA and mycotoxins.

Identification of the hub genes linked to zearalenone-induced hepatotoxicity in broiler chickens.

Zearalenone (ZEN) is a mycotoxin found in food and feed that impairs the function of multiple organs, especially the liver. However, the specific mechanisms through which ZEN induces liver damage in broiler chickens are not well understood. Therefore, this study aimed to identify the key genes linked to the hepatotoxicity induced by ZEN exposure in broiler chickens. Gene expression data from ZEN-treated and control chicken embryo primary hepatocytes (CEPHs) were used to implement differential expression analysis. Totally, 436 differentially expressed genes (DEGs) were detected, in which 223 and 213 genes were up- and down-regulated in ZEN-treated CEPHs, respectively. Gene ontology analysis suggested that these DEGs were involved in various biological processes, including chromosome segregation, mitotic cytokinesis, mitotic cell cycle, cell division, and mitotic spindle organization. Pathway analysis showed that the DEGs were associated with p53, FoxO, ubiquitin-mediated proteolysis, cell cycle, and mismatch repair signaling pathways. Furthermore, the hub genes, including BRCA1, CDC45, CDCA3, CDKN3, CENPE, CENPF, CENPI, CENPM, CENPU, and CEP55, potentially contributed to ZEN-induced hepatotoxicity. In conclusion, our study provides the valuable insight into the mechanism underlying ZEN-induced hepatotoxicity in broiler chickens.

Involvement of pro-inflammatory mediators and cell cycle disruption in neuronal cells induced by gliotoxin and ochratoxin A after individual and combined exposure.

Mycotoxins such as gliotoxin (GTX) and ochratoxin A (OTA) are secondary metabolites of Aspergillus and Penicillum found in food and feed. Both mycotoxins have shown to exert a detrimental effect on neuronal activity. The following study was carried out to elucidate the mechanisms by which GTX and OTA exert their toxicity. Non-differentiated SH-SY5Y neuronal-like cells were treated with GTX, OTA and their combinations to assess their cytotoxic effect using the MTT assay during 24, 48 and 72 h of exposure. Based on the results of the cytotoxic assays, cell cycle proliferation and immunological mediators were measured by determining the production of IL-6 and TNF-α using flow cytometry and ELISA, respectively. The IC50 values obtained were 1.24 and 1.35 µM when SH-SY5Y cells were treated with GTX at 48 h and 72 h, respectively. IC50 values of 8.25, 5.49 and 4.5 µM were obtained for OTA treatment at 24 h, 48 h and 72 h, respectively. The SubG0 phase increased in both treatments at 24 and 48 h. On the other hand, IL-6 and TNF-α production was increased in all mycotoxin treatments studied and was more pronounced for [GTX + OTA] after 48 h exposure. The additive and synergistic effect observed by the isobologram analysis between GTX and OTA resulted to a higher cytotoxicity which can be explained by the increased production of IL-6 and TNF-α inflammatory mediators that play an important role in the toxicity mechanism of these mycotoxins.

Cytotoxic Effects of Major and Emerging Mycotoxins on HepaRG Cells and Transcriptomic Response after Exposure of Spheroids to Enniatins B and B1.

Mycotoxins, produced by fungi, frequently occur at different stages in the food supply chain between pre- and postharvest. Globally produced cereal crops are known to be highly susceptible to contamination, thus constituting a major public health concern. Among the encountered mycotoxigenic fungi in cereals, Fusarium spp. are the most frequent and produce both regulated (i.e., T-2 toxin, deoxynivalenol -DON-, zearalenone -ZEA-) and emerging (i.e., enniatins -ENNs-, beauvericin -BEA-) mycotoxins. In this study, we investigated the in vitro cytotoxic effects of regulated and emerging fusariotoxins on HepaRG cells in 2D and 3D models using undifferentiated and differentiated cells. We also studied the impact of ENN B1 and ENN B exposure on gene expression of HepaRG spheroids. Gene expression profiling pinpointed the differentially expressed genes (DEGs) and overall similar pathways were involved in responses to mycotoxin exposure. Complement cascades, metabolism, steroid hormones, bile secretion, and cholesterol pathways were all negatively impacted by both ENNs. For cholesterol biosynthesis, 23/27 genes were significantly down-regulated and could be correlated to a 30% reduction in cholesterol levels. Our results show the impact of ENNs on the cholesterol biosynthesis pathway for the first time. This finding suggests a potential negative effect on human health due to the essential role this pathway plays.

Recalling the reported toxicity assessment of deoxynivalenol, mitigating strategies and its toxicity mechanisms: Comprehensive review.

Mycotoxins frequently contaminate a variety of food items, posing significant concerns for both food safety and public health. The adverse consequences linked to poisoning from these substances encompass symptoms such as vomiting, loss of appetite, diarrhea, the potential for cancer development, impairments to the immune system, disruptions in neuroendocrine function, genetic damage, and, in severe cases, fatality. The deoxynivalenol (DON) raises significant concerns for both food safety and human health, particularly due to its potential harm to vital organs in the body. It is one of the most prevalent fungal contaminants found in edible items used by humans and animals globally. The presence of harmful mycotoxins, including DON, in food has caused widespread worry. Altered versions of DON have arisen as possible risks to the environment and well-being, as they exhibit a greater propensity to revert back to the original mycotoxins. This can result in the buildup of mycotoxins in both animals and humans, underscoring the pressing requirement for additional investigation into the adverse consequences of these modified mycotoxins. Furthermore, due to the lack of sufficient safety data, accurately evaluating the risk posed by modified mycotoxins remains challenging. Our review study delves into conjugated forms of DON, exploring its structure, toxicity, control strategies, and a novel animal model for assessing its toxicity. Various toxicities, such as acute, sub-acute, chronic, and cellular, are proposed as potential mechanisms contributing to the toxicity of conjugated forms of DON. Additionally, the study offers an overview of DON's toxicity mechanisms and discusses its widespread presence worldwide. A thorough exploration of the health risk evaluation associated with conjugated form of DON is also provided in this discussion.

Comprehensive and cumulative risk evaluation of dietary exposure to aflatoxins and ochratoxin A on fermented teas worldwide by a new assessment model.

Recently, mycotoxin risks in fermented tea have received high attention, but mycotoxin transfer rates from tealeaf to infusion during brewing were rarely considered. In addition, the assessment data (i.e., mycotoxin occurrences and tea consumption) in previous assessments were usually limited. Here, a comprehensive and cumulative risk assessment of aflatoxins and ochratoxin A was performed using a tea assessment model, by which mycotoxin transfer rates were included and the assessment data were collected worldwide. By 10 times of brewing, the aflatoxin transfer rate was only 2.94% and OTA was 63.65%. Besides the extreme case, hazard quotients (HQs) from all consumers were lower than the threshold of 1.0, indicating no noncarcinogenic risk; the P95 cumulative margin of exposure (1/MoET) values were 2.52E-04 (30-39 years of age) and 2.42E-04 (≥50 years of age) for two high exposure groups under the upper bound scenario, which a little higher than the carcinogenic risk threshold of 1.00E-04. Notably, the P95 cumulative 1/MoET values (3.24E-03 -7.95E-03) by food assessment model were ten times higher than those of by tea assessment model. The comparative results showed that mycotoxin dietary risks on tea consumption by food assessment model were much overestimated. The result of this study indicated that the contaminants transfer rates should be considered for risk assessment on tea consumption in future work.

Evaluation of Immunomodulatory Effects of Fusarium Mycotoxins Using Bacterial Endotoxin-Stimulated Bovine Epithelial Cells and Macrophages in Co-Culture.

Mycotoxins are secondary metabolites produced by a variety of fungi that contaminate animal food and feeds and are capable of inducing a wide range of toxicities. Predictive in vitro models represent valuable substitutes for animal experiments to assess the toxicity of mycotoxins. The complexities of the interactions between epithelial and innate immune cells, vital for upholding barrier integrity and averting infections, remain inadequately understood. In the current study, a co-culture model of bovine epithelial cells (MAC-T) and macrophages (BoMac) was used to investigate the impact of exposure to Fusarium mycotoxins, namely deoxynivalenol (DON), zearalenone (ZEN), enniatin B (ENB), and beauvericin (BEA), on the inflammatory response elicited by the bacterial lipopolysaccharide (LPS) endotoxin. The MAC-T cells and BoMac were seeded on the apical side of a Transwell membrane and in the lower chamber, respectively, and mycotoxin exposure on the apical side of the membrane was carried out with the different mycotoxins (LC20; concentrations that elicited 20% cytotoxicity) for 48 h followed by an LPS immunity challenge for 24 h. The culture supernatants were collected from the basolateral compartment and these samples were submitted for cytokine/chemokine multiplex analysis. RNA-Seq analysis was performed using total RNA extracted from the MAC-T cells to acquire a more detailed insight into their cellular functions. The multiplex analysis indicated that IFN-γ, IL-1α, IL-8, and MCP-1 were significantly induced post-DON treatment when compared to control cells, and levels of IL-1α and IL-8 were enhanced significantly in all mycotoxin-treated groups post-LPS challenge. Analysis of the sequencing results showed that there were 341, 357, and 318 differentially expressed MAC-T cell genes that were up-regulated in the DON, ENB, and BEA groups, respectively. Gene ontology and pathway analysis revealed that these DEGs were significantly enriched in various biological processes and pathways related to inflammation, apoptosis signaling, and Wnt signaling. These results provide a comprehensive analysis of the co-culture cytokine/chemokine production and MAC-T cells' gene expression profiles elicited by Fusarium mycotoxins, which further contributes to the understanding of early endotoxemia post-mycotoxin exposure.

Endocrine Effect of Some Mycotoxins on Humans: A Clinical Review of the Ways to Mitigate the Action of Mycotoxins.

Fungi such as Aspergillus spp. and Fusarium spp., which are commonly found in the environment, pose a serious global health problem. This study aims to present the results of epidemiological studies, including clinical cases, on the relationship between human exposure to some mycotoxins, especially zearalenone and aflatoxin, and the occurrence of reproductive disorders. In addition, examples of methods to reduce human exposure to mycotoxins are presented. In March 2023, various databases (PubMed, Google Scholar, EMBASE and Web of Science) were systematically searched using Google Chrome to identify studies evaluating the association between exposure to mycotoxins and the occurrence of complications related to impaired fertility or cancer incidence. The analysed data indicate that exposure to the evaluated mycotoxins is widespread and correlates strongly with precocious puberty, reduced fertility and increased cancer incidence in women and men worldwide. There is evidence to suggest that exposure to the Aspergillus mycotoxin aflatoxin (AF) during pregnancy can impair intrauterine foetal growth, promote neonatal jaundice and cause perinatal death and preterm birth. In contrast, exposure to the Fusarium mycotoxin zearalenone (ZEA) leads to precocious sexual development, infertility, the development of malformations and the development of breast cancer. Unfortunately, the development of methods (biological, chemical or physical) to completely eliminate exposure to mycotoxins has limited practical application. The threat to human health from mycotoxins is real and further research is needed to improve our knowledge and specific public health interventions.

Neurotoxicity of ochratoxin A: Molecular mechanisms and neurotherapeutic strategies.

Data from epidemiological and experimental studies have evidenced that some chemical contaminants in food elicit their harmful effects by targeting the central nervous system. Ochratoxin A is a foodborne mycotoxin produced by Aspergillus and Penicillium species. Research on neurotoxicity associated with ochratoxin A exposure has increased greatly in recent years. The present review accrued substantial evidence on the neurotoxicity associated with ochratoxin A exposure as well as discussed notable susceptible targets of noxious ochratoxin A at molecular, cellular and genetic levels. Specifically, the neurotoxic mechanisms associated with ochratoxin A exposure were unequivocally unraveled in vitro using human neuroblastoma SH-SY5Y cells, mouse hippocampal HT22 cells, human astrocyte (NHA-SV40LT) cells and microglia cells as well as in vivo using mammalian and non-mammalian models. Data from human biomonitoring studies on plasma ochratoxin A levels in patients with neurodegenerative diseases with some age- and sex-related responses were also highlighted. Moreover, the neurotherapeutic mechanisms of some naturally occurring bioactive compounds against ochratoxin A neurotoxicity are reviewed. Collectively, accumulated data from literature demonstrate that ochratoxin A is a neurotoxin with potential pathological involvement in neurological disorders. Cutting edge original translational research on the development of neurotherapeutics for neurotoxicity associated with foodborne toxicants including ochratoxin A is indispensable.

Toxicity of the Mycotoxin Deoxynivalenol on Early Cleavage of Mouse Embryos by Fluorescence Intensity Analysis.

Deoxynivalenol is a mycotoxin, produced by Fusarium from contaminated corn, wheat, and other grains, that induces multiple effects in humans and animals, including cytotoxic, genotoxic, immunotoxic, and carcinogenic effects. Recent studies show that deoxynivalenol also affects the reproductive system of mammals, including oocyte quality. However, the effects of deoxynivalenol on early embryonic development have not been reported. In this study, fluorescence intensity analysis was used to show that deoxynivalenol disrupted the first cleavage of the zygote. The high deoxynivalenol dose disturbed the movement of the pronucleus after fertilization, while the low deoxynivalenol dose caused aberrant spindle morphology during the metaphase of the first cleavage. Further analysis showed that the reactive oxygen species level increased in the deoxynivalenol-exposed two-cell embryos, indicating oxidative stress. Moreover, deoxynivalenol caused DNA damage in the embryos, as positive γH2A.X signals were detected in the nucleus. These events led to the early apoptosis of mouse embryos, which was confirmed by autophagy. Taken together, our study provides evidence for the toxicity of deoxynivalenol during early embryonic development in the mouse model.

Mycotoxins in Cereal-Based Products and Their Impacts on the Health of Humans, Livestock Animals and Pets.

Cereal grains are the most important food staples for human beings and livestock animals. They can be processed into various types of food and feed products such as bread, pasta, breakfast cereals, cake, snacks, beer, complete feed, and pet foods. However, cereal grains are vulnerable to the contamination of soil microorganisms, particularly molds. The toxigenic fungi/molds not only cause quality deterioration and grain loss, but also produce toxic secondary metabolites, mycotoxins, which can cause acute toxicity, death, and chronic diseases such as cancer, immunity suppression, growth impairment, and neural tube defects in humans, livestock animals and pets. To protect human beings and animals from these health risks, many countries have established/adopted regulations to limit exposure to mycotoxins. The purpose of this review is to update the evidence regarding the occurrence and co-occurrence of mycotoxins in cereal grains and cereal-derived food and feed products and their health impacts on human beings, livestock animals and pets. The effort for safe food and feed supplies including prevention technologies, detoxification technologies/methods and up-to-date regulation limits of frequently detected mycotoxins in cereal grains for food and feed in major cereal-producing countries are also provided. Some important areas worthy of further investigation are proposed.

Cell cycle and enzymatic activity alterations induced by ROS production in human neuroblastoma cells SH-SY5Y exposed to Fumonisin B1, Ochratoxin A and their combination.

The presence of mycotoxins such as Fumonisin B1(FB1) and Ochratoxin A (OTA) in food and feed has become a threat to human and animal health since they can produce several afflictions. Different mechanisms of action by which they exercise their cytotoxic activity have been attributed to them, including the production of reactive oxygen species (ROS). For this reason, a measurement of the production of ROS species, and an evaluation of the intrinsic cell enzymatic antioxidant activity, including glutathione peroxidase (GPx), glutathione transferase (GTS), and catalase (CAT) together with a cytotoxicity and cell cycle assay have been performed in undifferentiated SH-SY5Y cells exposed to FB1, OTA and [FB1 + OTA] after 24 h and 48 h. FB1 and OTA. Monitoring of intracellular ROS production was carried out by the H2-DCFDA probe; while spectrometry analysis of absorbances was used for measuring GPx, GST and CAT activity. Finally, cell proliferation and cell cycle distribution were studied by flow cytometry. When cells were treated with OTA, an increase in GPx and GST activity was observed compared to FB1 and [FB1 + OTA]; conversely, a decrease in CAT activity was observed when cells were exposed to OTA coinciding with the results observed for ROS measurement. Regarding the cell cycle, when cells were exposed to OTA, a decrease in G0/G1 was detected, revealing an arrest of cell division for SH-SY5Y cells at the concentrations studied.

Efficacy of Feed Additive Containing Bentonite and Enzymatically Hydrolyzed Yeast on Intestinal Health and Growth of Newly Weaned Pigs under Chronic Dietary Challenges of Fumonisin and Aflatoxin.

This study aimed to investigate the efficacy of a feed additive containing bentonite and enzymatically hydrolyzed yeast on the intestinal health and growth of newly weaned pigs under chronic dietary exposure to fumonisin and aflatoxin. Newly weaned pigs were randomly allotted to one of four possible treatments: a control diet of conventional corn; a diet of corn contaminated with fumonisin and aflatoxin; a diet of mycotoxin-contaminated corn with 0.2% of feed additive; and a diet of mycotoxin contaminated corn with 0.4% of feed additive. We observed lower average weight gain and average daily feed intake in pigs that were fed only mycotoxin-contaminated corn compared to the control group. Feed additive supplementation linearly increased both average weight gain and feed intake, as well as tumor necrosis factor-alpha. In the jejunum, there was an observed decrease in immunoglobulin A and an increase in claudin-1. Additionally, feed additive supplementation increased the villus height to crypt depth ratio compared to the control. In conclusion, feed additives containing bentonite and enzymatically hydrolyzed yeast could mitigate the detrimental effects of mycotoxins on the growth performance of newly weaned pigs by improving intestinal integrity and positively modulating immune response.

Mutagenicity and genotoxicity assessment of the emerging mycotoxin Versicolorin A, an Aflatoxin B1 precursor.

Aflatoxin B1 (AFB1) is the most potent natural carcinogen among mycotoxins. Versicolorin A (VerA) is a precursor of AFB1 biosynthesis and is structurally related to the latter. Although VerA has already been identified as a genotoxin, data on the toxicity of VerA are still scarce, especially at low concentrations. The SOS/umu and miniaturised version of the Ames test in Salmonella Typhimurium strains used in the present study shows that VerA induces point mutations. This effect, like AFB1, depends primarily on metabolic activation of VerA. VerA also induced chromosomal damage in metabolically competent intestinal cells (IPEC-1) detected by the micronucleus assay. Furthermore, results from the standard and enzyme-modified comet assay confirmed the VerA-mediated DNA damage, and we observed that DNA repair pathways were activated upon exposure to VerA, as indicated by the phosphorylation and/or relocation of relevant DNA-repair biomarkers (γH2AX and 53BP1/FANCD2, respectively). In conclusion, VerA induces DNA damage without affecting cell viability at concentrations as low as 0.03 µM, highlighting the danger associated with VerA exposure and calling for more research on the carcinogenicity of this emerging food contaminant.

Deoxynivalenol: Emerging Toxic Mechanisms and Control Strategies, Current and Future Perspectives.

Deoxynivalenol (DON) is the most frequently present mycotoxin contaminant in food and feed, causing a variety of toxic effects in humans and animals. Currently, a series of mechanisms involved in DON toxicity have been identified. In addition to the activation of oxidative stress and the MAPK signaling pathway, DON can activate hypoxia-inducible factor-1α, which further regulates reactive oxygen species production and cancer cell apoptosis. Noncoding RNA and signaling pathways including Wnt/ß-catenin, FOXO, and TLR4/NF-κB also participate in DON toxicity. The intestinal microbiota and the brain-gut axis play a crucial role in DON-induced growth inhibition. In view of the synergistic toxic effect of DON and other mycotoxins, strategies to detect DON and control it biologically and the development of enzymes for the biodegradation of various mycotoxins and their introduction in the market are the current and future research hotspots.