Abstract
T-2 toxin is type A trichothecenes mycotoxin, which produced by fusarium species in cereal grains. T-2 toxin has been shown to induce a series of toxic effects on the health of human and animal, such as immunosuppression and carcinogenesis. Previous study has proven that T-2 toxin caused hepatotoxicity in chicken, but the regulatory mechanism is unclear. In the present study, we assessed the toxicological effect of T-2 toxin on apoptosis and autophagy in hepatocytes. The total of 120 1-day-old healthy broilers were allocated randomly into four groups and reared for 21 day with complete feed containing 0 mg/kg, 0.5 mg/kg, 1 mg/kg or 2 mg/kg T-2 toxin, respectively. The results showed that the apoptosis rate and pathological changes degree hepatocytes were aggravated with the increase of T-2 toxin. At the molecular mechanism level, T-2 toxin induced mitochondria-mediated apoptosis by producing reactive oxygen species, promoting cytochrome c translocation between the mitochondria and cytoplasm, and thus promoting apoptosomes formation. Meanwhile, the expression of the autophagy-related protein, ATG5, ATG7 and Beclin-1, and the LC3-II/LC3-I ratio were increased, while p62 was downregulated, suggesting T-2 toxin caused autophagy in hepatocytes. Further experiments demonstrated that the PI3K/AKT/mTOR signal may be participated in autophagy induced by T-2 toxin in chicken hepatocytes. These data suggest a possible underlying molecular mechanism for T-2 toxin that induces apoptosis and autophagy in chicken hepatocytes
Highlights
Mycotoxins are the main secondary metabolites of molds and lead to widespread contamination on crop plants and fruits
We examined the mitochondrial release of cytochrome during T-2 toxin-induced apoptosis
We found that the protein abundances of p70S6K, which are key proteins in the PI3K/Akt/mTOR pathway
Summary
Mycotoxins are the main secondary metabolites of molds and lead to widespread contamination on crop plants and fruits. Among the most important mycotoxins, T-2 toxin is a mycotoxin that can cause multiple effects in organisms [1]. T-2 toxin is a type A trichothecene produced by several. T-2 toxin leads to the effects of cytotoxin radiomimetic, which is due to impaired protein synthesis. T-2 toxin hampers synthesis of DNA and RNA in eukaryotic cells, which triggers cell apoptosis in vitro and in vivo [4]. Many studies have shown that T-2 toxin induces apoptotic cell death in hematopoietic tissue [5], spleen, liver [6], skin and intestinal crypt in mice [7]. Apoptosis induced by T-2 toxin was detected in the thymus, bursa of Fabricius and primary hepatocytes [8,9].
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