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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 -
Ecotoxicology and Environmental Safety Jul 2024Deoxynivalenol (DON) is one of the most common mycotoxins distributed in food and feed, which causes severe liver injury in humans and animals. Cold atmospheric plasma...
Deoxynivalenol (DON) is one of the most common mycotoxins distributed in food and feed, which causes severe liver injury in humans and animals. Cold atmospheric plasma (CAP) has received much attention in mycotoxin degradation due to the advantages of easy operation, high efficiency, and low temperature. So far, the majority of studies have focused on the degradation efficiency and mechanism of CAP on DON, while there is still little information available on the hepatotoxicity of DON after CAP treatment. Herein, this study aimed to investigate the effect of CAP on DON-induced hepatotoxicity both in vitro and in vivo and its underlying mechanisms. The results showed that 120-s CAP treatment achieved 97 % degradation of DON. The vitro hepatotoxicity of DON in L02 cells was significantly reduced with CAP treatment time. Meanwhile, CAP markedly alleviated DON-induced liver injury in mice including the balloon-like degeneration of liver tissues and elevation of AST and ALP level. The underlying mechanism for CAP detoxification of DON-induced hepatotoxicity was further elucidated. The results showed that DON caused severe oxidative stress in cells by suppressing the antioxidant signaling pathway of Nrf2/HO-1/NQO-1, consequently leading to mitochondrial dysfunction and cell apoptosis, accompanied by cellular senescence and inflammation. CAP blocked DON inhibition on the Nrf2/HO-1/NQO-1 signaling pathway through the efficient degradation of DON, accordingly alleviating the oxidative stress and liver injury induced by DON. Therefore, CAP is an effective method to eliminate DON hepatotoxicity, which can be applied in the detoxification of mycotoxin-contaminated food and feed to ensure human and animal health.
Topics: Animals; Plasma Gases; Mice; Trichothecenes; Chemical and Drug Induced Liver Injury; Oxidative Stress; Liver; Apoptosis; Male; Humans; Inactivation, Metabolic; Cell Line
PubMed: 38843744
DOI: 10.1016/j.ecoenv.2024.116547 -
Food Chemistry May 2024Citrinin is a hepato-nephrotoxic mycotoxin produced by fungal species. The Monascus purpureus fungus plays a crucial role in the fermentation of red rice to produce red...
Development and validation of an analytical method for determination of citrinin in red rice and red yeast rice-based food supplements by ultra-high performance liquid chromatography tandem mass spectrometry.
Citrinin is a hepato-nephrotoxic mycotoxin produced by fungal species. The Monascus purpureus fungus plays a crucial role in the fermentation of red rice to produce red yeast rice-based food supplements, which represent the primary source of human exposure to citrinin. In this study, a simple and sensitive analytical method was successfully developed and validated for the citrinin determination in these products. The extraction process involved a QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) step and citrinin determination by ultra high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). The proposed method provided satisfactory linearity, percentage of recovery from 82 to 104% with relative standard deviations (RSD) lower than 14%, and limits of detection and quantification of 0.07 μg/Kg and 0.24 μg/kg, respectively. Among the 14 samples analyzed, citrinin was found in two red rice samples (0.24 and 0.46 μg/kg) and in six food supplements (from 0.44 to 87 μg/kg).
PubMed: 38843711
DOI: 10.1016/j.foodchem.2024.139941 -
Food Microbiology Sep 2024Penicillium spp. produce a great variety of secondary metabolites, including several mycotoxins, on food substrates. Chestnuts represent a favorable substrate for...
Penicillium spp. produce a great variety of secondary metabolites, including several mycotoxins, on food substrates. Chestnuts represent a favorable substrate for Penicillium spp. development. In this study, the genomes of ten Penicillium species, virulent on chestnuts, were sequenced and annotated: P. bialowiezense. P. pancosmium, P. manginii, P. discolor, P. crustosum, P. palitans, P. viridicatum, P. glandicola, P. taurinense and P. terrarumae. Assembly size ranges from 27.5 to 36.8 Mb and the number of encoded genes ranges from 9,867 to 12,520. The total number of predicted biosynthetic gene clusters (BGCs) in the ten species is 551. The most represented families of BGCs are non ribosomal peptide synthase (191) and polyketide synthase (175), followed by terpene synthases (87). Genome-wide collections of gene phylogenies (phylomes) were reconstructed for each of the newly sequenced Penicillium species allowing for the prediction of orthologous relationships among our species, as well as other 20 annotated Penicillium species available in the public domain. We investigated in silico the presence of BGCs for 10 secondary metabolites, including 5 mycotoxins, whose production was validated in vivo through chemical analyses. Among the clusters present in this set of species we found andrastin A and its related cluster atlantinone A, mycophenolic acid, patulin, penitrem A and the cluster responsible for the synthesis of roquefortine C/glandicoline A/glandicoline B/meleagrin. We confirmed the presence of these clusters in several of the Penicillium species conforming our dataset and verified their capacity to synthesize them in a chestnut-based medium with chemical analysis. Interestingly, we identified mycotoxin clusters in some species for the first time, such as the andrastin A cluster in P. flavigenum and P. taurinense, and the roquefortine C cluster in P. nalgiovense and P. taurinense. Chestnuts proved to be an optimal substrate for species of Penicillium with different mycotoxigenic potential, opening the door to risks related to the occurrence of multiple mycotoxins in the same food matrix.
Topics: Penicillium; Mycotoxins; Multigene Family; Secondary Metabolism; Genome, Fungal; Phylogeny; Food Contamination; Patulin; Fungal Proteins; Nuts; Polyketide Synthases; Food Microbiology; Corylus; Heterocyclic Compounds, 4 or More Rings; Indoles; Piperazines
PubMed: 38839238
DOI: 10.1016/j.fm.2024.104532 -
Frontiers in Plant Science 2024Fusarium crown rot (FCR) is an important and devastating disease of wheat () caused by the fungus and related pathogens. Using two distinct susceptible cultivars, we...
Fusarium crown rot (FCR) is an important and devastating disease of wheat () caused by the fungus and related pathogens. Using two distinct susceptible cultivars, we investigated the isolation frequencies of and quantified its biomass accumulation and the levels of the associated toxins deoxynivalenol (DON) and DON-3-glucoside (D3G) in inoculated field-grown wheat plants. We detected in stem, peduncle, rachis, and husk tissues, but not in grains, whereas DON and D3G accumulated in stem, rachis, husk, and grain tissues. Disease severity was positively correlated with the frequency of pathogen isolation, biomass, and mycotoxin levels. The amount of biomass and mycotoxin contents in asymptomatic tissue of diseased plants were associated with the distance of the tissue from the diseased internode and the disease severity of the plant. Thus, apparently healthy tissue may harbor and contain associated mycotoxins. This research helps clarify the relationship between occurrence, biomass, and mycotoxin accumulation in tissues of susceptible wheat cultivars with or without disease symptoms, providing information that can lead to more effective control measures.
PubMed: 38835863
DOI: 10.3389/fpls.2024.1356723 -
Neurotoxicology Jun 2024The rate of medical cannabis use has increased in parallel with the number of states legalizing its use. Parkinson's disease (PD) patients are of particular concern due...
The rate of medical cannabis use has increased in parallel with the number of states legalizing its use. Parkinson's disease (PD) patients are of particular concern due to their higher cannabis use rate than in the general US population (25-40 % PD patient cannabis users vs. ∼18 % in the general population), as well as their susceptibility to environmental contaminants in cannabis, including pesticides, toxic elements, solvents, microbes, and mycotoxins. In order to address the complex nature of this industry, we examined the changes in PD-related qualifying conditions in the U.S. from 2019 to 2023. We also conducted an online survey to gain insight into the knowledge, risk perceptions, and opinions regarding medical cannabis and contamination issues from physicians who treated PD patients. The number of states including PD-related qualifying conditions increased over the past 5 years from 28 to 36 states. These conditions included PD (increasing from 14 to 16 states), muscle spasms (14 to 24), anxiety (1 to 5), and pain (17 to 35). State-by-state comparisons revealed high variability in the language used to describe the different qualifying conditions. Online surveys were sent out to 45 neurologists and movement disorder specialists who primarily treated PD patients. The response rate was 44 % from nine states (AZ, CA, FL, MA, MN, WI, PA, IL, and NM). When asked if they were aware of any contaminants in cannabis products, we found that 65 % of the physicians were unaware of any contaminants commonly found in cannabis and only 25 %, 15 %, and 15 % of them were aware of pesticide, toxic element, and solvent contaminants, respectively. In their free-text opinion response on the health impact of cannabis-borne contaminants, "long-term effect" (35 %) and "comorbidities and PD prognosis" (40 %) were identified as the two most common themes. These results point to the need for further regulatory deliberation regarding risks and susceptibility to cannabis contaminants. Additionally, education is needed to inform physicians on cannabis safety issues. Further research will identify the implementation strategies to reduce contaminant exposure and protect patient health.
PubMed: 38834158
DOI: 10.1016/j.neuro.2024.05.008 -
Ecotoxicology and Environmental Safety Jul 2024Aflatoxin B (AFB) is known to inhibit growth, and inflict hepatic damage by interfering with protein synthesis. Allicin, has been acknowledged as an efficacious...
Aflatoxin B (AFB) is known to inhibit growth, and inflict hepatic damage by interfering with protein synthesis. Allicin, has been acknowledged as an efficacious antioxidant capable of shielding the liver from oxidative harm. This study aimed to examine the damage caused by AFB on bovine hepatic cells and the protective role of allicin against AFB-induced cytotoxicity. In this study, cells were pretreated with allicin before the addition of AFB for co-cultivation. Our findings indicate that AFB compromises cellular integrity, suppresses the expression of nuclear factor erythroid 2-related factor 2 (Nrf2). In addition, allicin attenuates oxidative damage to bovine hepatic cells caused by AFB by promoting the expression of the Nrf2 pathway and reducing cell apoptosis. In conclusion, the results of this study will help advance clinical research and applications, providing new options and directions for the prevention and treatment of liver diseases.
Topics: Animals; Sulfinic Acids; Aflatoxin B1; Cattle; Disulfides; NF-E2-Related Factor 2; Signal Transduction; Hepatocytes; Oxidative Stress; Apoptosis; Antioxidants; Female
PubMed: 38833978
DOI: 10.1016/j.ecoenv.2024.116527 -
Cell Biology and Toxicology Jun 2024Hippocampal neurons maintain the ability of proliferation throughout life to support neurogenesis. Deoxynivalenol (DON) is a mycotoxin that exhibits brain toxicity, yet...
Hippocampal neurons maintain the ability of proliferation throughout life to support neurogenesis. Deoxynivalenol (DON) is a mycotoxin that exhibits brain toxicity, yet whether and how DON affects hippocampal neurogenesis remains unknown. Here, we use mouse hippocampal neuron cells (HT-22) as a model to illustrate the effects of DON on neuron proliferation and to explore underlying mechanisms. DON exposure significantly inhibits the proliferation of HT-22 cells, which is associated with an up-regulation of cell cycle inhibitor p21 at both mRNA and protein levels. Global and site-specific mA methylation levels on the 3'UTR of p21 mRNA are significantly increased in response to DON treatment, whereas inhibition of mA hypermethylation significantly alleviates DON-induced cell cycle arrest. Further mechanistic studies indicate that the mA readers YTHDF1 and IGF2BP1 are responsible for mA-mediated increase in p21 mRNA stability. Meanwhile, 3'UTR of E3 ubiquitin ligase TRIM21 mRNA is also mA hypermethylated, and another mA reader YTHDF2 binds to the mA sites, leading to decreased TRIM21 mRNA stability. Consequently, TRIM21 suppression impairs ubiquitin-mediated p21 protein degradation. Taken together, mA-mediated upregulation of p21, at both post-transcriptional and post-translational levels, contributes to DON-induced inhibition of hippocampal neuron proliferation. These results may provide new insights for epigenetic therapy of neurodegenerative diseases.
Topics: Animals; Trichothecenes; Hippocampus; Mice; Neurons; Cyclin-Dependent Kinase Inhibitor p21; Up-Regulation; Cell Proliferation; RNA-Binding Proteins; Cell Line; 3' Untranslated Regions; Neurogenesis; RNA, Messenger; RNA Stability; Cell Cycle Checkpoints; Ribonucleoproteins; Methylation
PubMed: 38833095
DOI: 10.1007/s10565-024-09872-7