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Toxicology Jun 2024Monitoring modifications in membrane lipids in association with external stimuli/agents, including fumonisins (FUMs), is a widely employed approach to assess cellular... (Review)
Review
Monitoring modifications in membrane lipids in association with external stimuli/agents, including fumonisins (FUMs), is a widely employed approach to assess cellular metabolic response/status. FUMs are prevalent fusariotoxins worldwide that have diverse structures with varying toxicity across species; nevertheless, they can induce metabolic disturbances and disease, including cancer. The capacity of FUMs to disrupt membrane lipids, demonstrated across numerous species and organs/tissues, is ascribed to a multitude of factors/events, which range from direct to indirect effects. Certain events are well established, whereas the potential consequences of others remain speculative. The most notable effect is their resemblance to sphingoid bases, which impacts the synthesis of ceramides leading to numerous changes in lipids' composition not limited to sphingolipids' composition of the membranes. The next plausible scenario involves the induction of oxidative stress, which is considered an indirect/secondary effect of FUMs. Additional modes of action include modifications of enzyme activities and nuclear signals related to lipid metabolism, although these are likely not yet fully comprehended. This review provides in-depth insight into the current state of these events and their potential mechanistic actions in modifying membrane lipids, with a focus on long-chain fatty acids. This paper also presents a detailed description of the reported modifications to membrane lipids by FUMs.
PubMed: 38871209
DOI: 10.1016/j.tox.2024.153860 -
Food Chemistry Jun 2024Natural toxins, such as mycotoxins and cyanotoxins, can contaminate food and feed, leading to toxicity in humans and animals. This study focused on using nine magnetic...
Natural toxins, such as mycotoxins and cyanotoxins, can contaminate food and feed, leading to toxicity in humans and animals. This study focused on using nine magnetic nanostructured agents to remove the main types of toxins. Initially, the efficacy of these materials was evaluated in water solutions, revealing that composites with sizes below 3 mm, containing magnetite, activated carbon, esterified pectin, and sodium alginate, removed up to 90% of mycotoxins and cyanotoxins with an adsorption of 873 ng/g. The application of the nanostructures was then assessed in beer, milk, Distillers Dried Grains with Solubles and water contaminated with cyanobacteria. The presence of matrix slightly decreases the adsorption capacity for some toxins. The maximum toxin removal capacity was calculated with cyanotoxins, composites achieved a removal of up to 0.12 mg/g, while nanocomposites (15 μm) reached 36.6 mg/g. Therefore, these findings point out the potential for using nanotechnology in addressing natural toxins contamination.
PubMed: 38870813
DOI: 10.1016/j.foodchem.2024.140004 -
Toxicon : Official Journal of the... Jun 2024This case report investigated the outbreak of aflatoxicosis in a dairy herd in Pakistan, which resulted in 30 abortions of 40 confirmed (75%) pregnant cows in a period...
This case report investigated the outbreak of aflatoxicosis in a dairy herd in Pakistan, which resulted in 30 abortions of 40 confirmed (75%) pregnant cows in a period of 35 days and in 18.8% depression of farm average milk production for the entire herd. The analysis of the concentrate feed of the total mixed ration (TMR), using enzyme-linked immunosorbent assay (ELISA) procedures from two different local laboratories, indicated concentrations of 60 μg/kg dry matter (DM) of aflatoxin B1 (AFB1) and 100 μg/kg DM of total aflatoxins (AFs: sum of B1, B2, G1 and G2). Subsequently, a confirmatory analysis with a more sensitive and validated multi-metabolite liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was performed. This analysis detected a concentration of total AFs in the TMR of 166 μg/kg DM ± 3.5 (AFB1:134, AFB2:17.4 and AFM1:14.9 μg/kg DM). The concentrate feed (55% of the TMR DM) was confirmed as a source of contamination, presenting a concentration >29 times higher than the EU-maximum limit value (5.68 μg/kg DM). Additionally, the multi-mycotoxin analysis evidenced the co-occurrence of 81 other toxic and potentially toxic fungal metabolites in the fed TMR. After replacing the contaminated concentrate feed with feedstuffs of the same formulation but from a new charge of ingredients, the abortion episodes ceased, and milk production increased significantly. In conclusion, the data of this case report suggest that AFs may be associated with pregnancy losses in dairy cattle and milk production depression. From the public health perspective, the data also indicate the need for a more careful examination of dairy animal feed in Pakistan. Since the high concentration of AFB1 detected in feed and considering the literature-reported transfer rates (1-6%) of this toxin to AFM1 (carcinogen for humans) in milk, the milk produced during the outbreak period is expected to be contaminated with AFM1, which raises public health concerns.
PubMed: 38866254
DOI: 10.1016/j.toxicon.2024.107799 -
MBio Jun 2024Plant pathogenic fungi cause serious diseases, which result in the loss of crop yields and reduce the quality of crops worldwide. To counteract the escalating risks of...
Plant pathogenic fungi cause serious diseases, which result in the loss of crop yields and reduce the quality of crops worldwide. To counteract the escalating risks of chemical fungicides, interest in biological control agents to manage plant diseases has significantly increased. In this study, we comprehensively screened microbial culture filtrates using a yeast screening system to find microbes exhibiting respiratory inhibition activity. Consequently, we found a soil-borne microbe HK544 strain exhibiting a respiration inhibitory activity and identified edeine B (EB) from the culture filtrate of HK544 as the active compound of the respiration inhibition activity. Furthermore, against a plant pathogenic fungus , our results showed that EB has effects on multiple aspects of respiration with the downregulation of most of the mitochondrial-related genes based on transcriptome analysis, differential EB-sensitivity from targeted mutagenesis, and the synergistic effects of EB with electron transport chain complex inhibitors. With the promising plant disease control efficacy of HK544 producing EB, our results suggest that HK544 has potential as a biocontrol agent for Fusarium head blight.IMPORTANCEAs a necrotrophic fungus, is a highly destructive pathogen causing severe diseases in cereal crops and mycotoxin contamination in grains. Although chemical control is considered the primary approach to control plant disease caused by , fungicide-resistant strains have been detected in the field after long-term continuous application of fungicides. Moreover, applying chemical fungicides that trigger mycotoxin biosynthesis is a great concern for many researchers. Biocontrol of head blight (FHB) by biological control agents (BCAs) represents an alternative approach and could be used as part of the integrated management of FHB and mycotoxin production. The most extensive studies on bacterial BCAs-fungal communications in agroecosystems have focused on antibiosis. Although many BCAs in agricultural ecology have already been used for fungal disease control, the molecular mechanisms of antibiotics produced by BCAs remain to be elucidated. Here, we found a potential BCA ( HK544) with a strong antifungal activity based on the respiration inhibition activity with its active compound edeine B (EB). Furthermore, our results showed that EB secreted by HK544 suppresses the expression of the mitochondria-related genes of , subsequently suppressing fungal development and the virulence of . In addition, EB exhibited a synergism with complex I inhibitors such as rotenone and fenazaquin. Our work extends our understanding of how HK544 exhibits antifungal activity and suggests that the HK544 strain could be a valuable source for developing new crop protectants to control .
PubMed: 38860787
DOI: 10.1128/mbio.01351-24 -
Scientific Reports Jun 2024Zearalenone (ZEN), an estrogenic mycotoxin, is one of the most common food and feed contaminants. Also, its metabolites α-zearalenol (α-ZEL) and β-zearalenol (β-ZEL)...
Zearalenone (ZEN), an estrogenic mycotoxin, is one of the most common food and feed contaminants. Also, its metabolites α-zearalenol (α-ZEL) and β-zearalenol (β-ZEL) are considered to induce oxidative stress, however its effect in prostate cells is not known yet. Our previous observations showed that forehead box transcription factor 3a (FOXO3a) expression is modified in hormone- sensitive cells in the response to mycotoxins, similar to the phosphoinositide 3-kinase (PI3K)/ protein kinase B (Akt) pathway. Thus, this study evaluated the direct molecular effect of α-ZEL and β-ZEL in a dose of 30 µM in hormone-dependent human prostate cancer (PCa) cells with the focus of the involvement of FOXO3a and PI3K/Akt signaling pathway in that effect. We observed that both active metabolites of ZEN reduced cell viability, induced oxidative stress, cell cycle arrest and apoptosis in PCa cells. Furthermore, we observed that FOXO3a as well as PI3K/Akt signaling pathway participate in ZELs induced toxicity in PCa cells, indicating that this signaling pathway might be a regulator of mycotoxin-induced toxicity generally.
Topics: Humans; Proto-Oncogene Proteins c-akt; Apoptosis; Forkhead Box Protein O3; Signal Transduction; Phosphatidylinositol 3-Kinases; Reactive Oxygen Species; Oxidative Stress; Zeranol; Cell Line, Tumor; Zearalenone; Cell Survival; Male; Prostatic Neoplasms
PubMed: 38858492
DOI: 10.1038/s41598-024-64350-8 -
Journal of Dairy Science Jun 2024The aim of this study was to evaluate the effects of different anti-mycotoxin feed additives on the concentration of mycotoxins in milk, urine, and blood plasma of dairy...
Anti-mycotoxin feed additives: effects on metabolism, mycotoxin excretion, performance, and total tract digestibility of dairy cows fed artificially multi-mycotoxin-contaminated diets.
The aim of this study was to evaluate the effects of different anti-mycotoxin feed additives on the concentration of mycotoxins in milk, urine, and blood plasma of dairy cows fed artificially multi-mycotoxin-contaminated diets. Secondarily, performance, total-tract apparent digestibility of nutrients, and blood parameters were evaluated. Twelve multiparous cows (165 ± 45 d in milk, 557 ± 49 kg body weight, and 32.1 ± 4.57 kg/d milk yield at the start of the experiment) were blocked according to parity, milk yield, and days in milk and used in a 4 × 4 Latin square design experiment with 21-d periods, where the last 7 d were used for sampling and data analysis. Treatments were: 1) Mycotoxin group (MTX), basal diet (BD) without anti-mycotoxin feed additives; 2) Hydrated sodium calcium aluminosilicate (HSCA), HSCA added to the BD at 25g/cow/d; 3) Mycotoxin deactivator 15 (MD15), MD (Mycofix® Plus, dsm-firmenich) added to the BD at 15 g/cow/d; and 4) Mycotoxin deactivator 30 (MD30), MD added to the BD at 30 g/cow/d. Cows from all treatments were challenged with a blend of mycotoxins containing 404 μg aflatoxins B1 (AFB1), 5,025 μg deoxynivalenol (DON), 8,046 μg fumonisins (FUM), 195 μg T2 toxin (T2), and 2,034 μg of zearalenone (ZEN) added daily to the BD during the last 7 d of each period. Neither performance (milk yield and composition) nor nutrient digestibility was affected by treatments. All additives reduced aflatoxin M1 (AFM1) concentration in milk, whereas MD15 and MD30 group had lower excretion of AFM1 in milk than HSCA. DON, FUM, T2, or ZEN were not detected in milk of MD15 and MD30. Concentrations in milk of DON, FUM, T2, and ZEN were similar between MTX and HSCA. Except for AFM1, none of the analyzed mycotoxins were detected in urine of MD30 group. Comparing HSCA to MD treatments, the concentration of AFM1 was greater for HSCA, whereas MD30 was more efficient at reducing AFM1 in urine than MD15. AFM1, DON, FUM, and ZEN were not detected in the plasma of cows fed MD30, and DON was also not detected in MD15 group. Plasma concentration of FUM was lower for MD15, similar plasma FUM concentration was reported for HSCA and MTX. Plasma concentration of ZEN was lower for MD15 than MTX and HSCA. Serum concentrations of haptoglobin and hepatic enzymes were not affected by treatments. Blood concentration of sodium was lower in HSCA compared with MD15 and MD30 groups. In conclusion, the mycotoxin deactivator proved to be effective in reducing the secretion of mycotoxins in milk, urine, and blood plasma, regardless of the dosage. This reduction was achieved without adverse effects on milk production or total-tract digestibility in cows fed multi-mycotoxin-contaminated diets over a short-term period. Greater reductions in mycotoxin secretion were observed with full dose of MD.
PubMed: 38851567
DOI: 10.3168/jds.2023-24539 -
Journal of the Neurological Sciences Jun 2024Nodding syndrome is an epileptic encephalopathy associated with neuroinflammation and tauopathy. This initially pediatric brain disease, which has some clinical overlap...
Nodding syndrome is an epileptic encephalopathy associated with neuroinflammation and tauopathy. This initially pediatric brain disease, which has some clinical overlap with Methyl-CpG-binding protein 2 (MECP2) Duplication Syndrome, has impacted certain impoverished East African communities coincident with local civil conflict and internal displacement, conditions that forced dependence on contaminated food and water. A potential role in Nodding syndrome for certain biotoxins (freshwater cyanotoxins plus/minus mycotoxins) with neuroinflammatory, excitotoxic, tauopathic, and MECP2-dysregulating properties, is considered here for the first time.
PubMed: 38850769
DOI: 10.1016/j.jns.2024.123077 -
Clinical Kidney Journal Jun 2024A 47-year-old woman developed severe kidney dysfunction after taking a lipid-lowering supplement, Red Yeast Rice Cholestehelp, for approximately 7 months. The patient...
A 47-year-old woman developed severe kidney dysfunction after taking a lipid-lowering supplement, Red Yeast Rice Cholestehelp, for approximately 7 months. The patient developed sudden nausea and had an elevated serum creatinine level of 4.26 mg/dL. A kidney biopsy showed findings consistent with acute tubular necrosis. Kidney dysfunction improved with discontinuation of supplementation, and corticosteroid therapy. Similar kidney involvement has been reported, raising concerns regarding supplements in Japan. An investigation of the nephrotoxic ingredients in the same product batches is currently underway. This report underscores the need for public awareness and warnings of health risk concerns associated with unregulated supplements.
PubMed: 38846105
DOI: 10.1093/ckj/sfae151 -
Journal of Animal Science and... Jun 2024The intestinal epithelium performs essential physiological functions, such as nutrient absorption, and acts as a barrier to prevent the entry of harmful substances....
BACKGROUND
The intestinal epithelium performs essential physiological functions, such as nutrient absorption, and acts as a barrier to prevent the entry of harmful substances. Mycotoxins are prevalent contaminants found in animal feed that exert harmful effects on the health of livestock. Zearalenone (ZEA) is produced by the Fusarium genus and induces gastrointestinal dysfunction and disrupts the health and immune system of animals. Here, we evaluated the molecular mechanisms that regulate the effects of ZEA on the porcine intestinal epithelium.
RESULTS
Treatment of IPEC-J2 cells with ZEA decreased the expression of E-cadherin and increased the expression of Snai1 and Vimentin, which induced Snail1-mediated epithelial-to-mesenchymal transition (EMT). In addition, ZEA induces Snail-mediated EMT through the activation of TGF-β signaling. The treatment of IPEC-J2 cells with atractylenolide III, which were exposed to ZEA, alleviated EMT.
CONCLUSIONS
Our findings provide insights into the molecular mechanisms of ZEA toxicity in porcine intestinal epithelial cells and ways to mitigate it.
PubMed: 38845033
DOI: 10.1186/s40104-024-01038-z -
Environmental Toxicology and... Jun 2024Among cereal contaminants, mycotoxins are of concern due to their importance in terms of food and feed safety. The difficulty in establishing a diagnosis for... (Review)
Review
Among cereal contaminants, mycotoxins are of concern due to their importance in terms of food and feed safety. The difficulty in establishing a diagnosis for mycotoxicosis relies on the fact that the effects are most often subclinical for chronic exposure and the most common scenario is multi-contamination by various toxins. Mycotoxin co-occurrence is a major food safety concern as additive or even synergic toxic impacts may occur, but also regarding current regulations as they mainly concern individual mycotoxin levels in specific foods and feed in the food chain. However, due to the large number of possible mycotoxin combinations, there is still limited knowledge on co-exposure toxicity data, which depends on several parameters. In this context, this systematic review aims to provide an overview of the toxic effects of two regulated mycotoxins, namely ochratoxin A and fumonisin B1. This review focused on the 2012-2022 period and analysed the occurrence in Europe of the selected mycotoxins in different food matrices (cereals and cereal-derived products), and their toxic impact, alone or in combination, on in vitro intestinal and hepatic human cells. To better understand and evaluate the associated risks, further research is needed using new approach methodologies (NAM), such as in vitro 3D models. KEY CONTRIBUTION: Cereals and their derived products are the most important food source for humans and feed for animals worldwide. This manuscript is a state of the art review of the literature over the last ten years on ochratoxin A and fumonisin B1 mycotoxins in these products in Europe as well as their toxicological effects, alone and in combination, on human cells. Future perspectives and some challenges regarding the assessment of toxicological effects of mycotoxins are also discussed.
PubMed: 38844151
DOI: 10.1016/j.etap.2024.104489