T-2 toxin and deoxynivalenol (DON) are type A and B trichothecenes, respectively. They widely occur as pollutants in food and crops and cause a series of toxicities, including immunotoxicity, hepatotoxicity, and neurotoxicity. Oxidative stress is the primary mechanistic basis of these toxic effects. Increasing amounts of evidence have shown that mitochondria are significant targets of apoptosis caused by T-2 toxin- and DON-induced oxidative stress via regulation of Bax/B-cell lymphoma-2 and caspase-3/caspase-9 signaling. DNA methylation and autophagy are involved in oxidative stress related to apoptosis, and hypoxia and immune evasion are related to oxidative stress in this context. Hypoxia induces oxidative stress by stimulating mitochondrial reactive oxygen species production and regulates the expression of cytokines, such as interleukin-1β and tumor necrosis factor-α. Programmed cell death-ligand 1 is upregulated by these cytokines and by hypoxia-inducible factor-1, which allows it to bind to programmed cell death-1 to enable escape of immune cell surveillance and achievement of immune evasion. This review concentrates on novel findings regarding the oxidative stress mechanisms of the trichothecenes T-2 toxin and DON. Importantly, we discuss the new evidence regarding the connection of hypoxia and immune evasion with oxidative stress in this context. Finally, the trinity of hypoxia, oxidative stress and immune evasion is highlighted. This work will be conducive to an improved understanding of the oxidative stress caused by trichothecene mycotoxins.

• Klíčová slova
• Deoxynivalenol, Hypoxia, Immune evasion, Oxidative stress, T-2 toxin,
• MeSH
• apoptóza účinky léků   MeSH
• hypoxie chemicky indukované   MeSH
• imunitní únik účinky léků   MeSH
• lidé MeSH
• mitochondrie účinky léků   patologie   MeSH
• oxidační stres účinky léků   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• T-2 toxin toxicita   MeSH
• trichotheceny toxicita   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• deoxynivalenol MeSH Prohlížeč
• reaktivní formy kyslíku MeSH
• T-2 toxin MeSH
• trichotheceny MeSH

Oxidative stress is closely linked to the toxic responses of various cell types in normal and pathophysiological conditions. Deoxynivalenol (DON), an inducer of stress responses in the ribosome and the endoplasmic reticulum (ER), causes mitochondrial dysfunction and mitochondria-dependent apoptosis through oxidative stress in humans and animals. The NF-κB pathway, which is closely linked to oxidative stress, is hypothesized to be a critical signaling pathway for DON-induced toxicity and is a potential target for intervention. The present study was conducted to explore the protective effects of pyrrolidine dithiocarbamate (PDTC) from the toxic effects of DON in rat anterior pituitary GH3 cells. Our results showed that DON activated the NF-κB transcription factors and induced cellular oxidative stress, mitochondrial dysfunction, and apoptosis. Morphological studies using transmission electron microscopy (TEM) and cell apoptosis analyses suggested that PDTC prevented DON-induced mitochondrial dysfunction and apoptosis, probably by preventing the DON-induced translocation of NF-κB p65 into the nucleus, and by inhibiting DON-induced iNOS expression. This led to the blocking of the NF-κB pathway and inhibition of iNOS activity.

• MeSH
• antioxidancia MeSH
• apoptóza MeSH
• lidé MeSH
• mitochondrie metabolismus   MeSH
• NF-kappa B metabolismus   MeSH
• oxidační stres MeSH
• pyrrolidiny farmakologie   terapeutické užití   MeSH
• signální transdukce MeSH
• thiokarbamáty farmakologie   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antioxidancia MeSH
• NF-kappa B MeSH
• pyrrolidine dithiocarbamic acid MeSH Prohlížeč
• pyrrolidiny MeSH
• thiokarbamáty MeSH

Trichothecenes are a group of mycotoxins mainly produced by fungi of genus Fusarium. Due to high toxicity and widespread dissemination, T-2 toxin and deoxynivalenol (DON) are considered to be the most important compounds of this class. Trichothecenes generate free radicals, including reactive oxygen species (ROS), which induce lipid peroxidation, decrease levels of antioxidant enzymes, and ultimately lead to apoptosis. Consequently, oxidative stress is an active area of research on the toxic mechanisms of trichothecenes, and identification of antioxidant agents that could be used against trichothecenes is crucial for human health. Numerous natural compounds have been analyzed and have shown to function very effectively as antioxidants against trichothecenes. In this review, we summarize the molecular mechanisms underlying oxidative stress induced by these compounds, and discuss current knowledge regarding such antioxidant agents as vitamins, quercetin, selenium, glucomannan, nucleotides, antimicrobial peptides, bacteria, polyunsaturated fatty acids, oligosaccharides, and plant extracts. These products inhibit trichothecene-induced oxidative stress by (1) inhibiting ROS generation and induced DNA damage and lipid peroxidation; (2) increasing antioxidant enzyme activity; (3) blocking the MAPK and NF-κB signaling pathways; (4) inhibiting caspase activity and apoptosis; (5) protecting mitochondria; and (6) regulating anti-inflammatory actions. Finally, we summarize some decontamination methods, including bacterial and yeast biotransformation and degradation, as well as mycotoxin-binding agents. This review provides a comprehensive overview of antioxidant agents against trichothecenes and casts new light on the attenuation of oxidative stress.

• Klíčová slova
• T-2 toxin, antioxidant agents, deoxynivalenol, oxidative stress, trichothecenes,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH