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

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Summary

Introduction

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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