Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, Sichuan, China.
Toxins (Basel). 2020 Jan 29;12(2):90. doi: 10.3390/toxins12020090.
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.
T-2 毒素是 A 型单端孢霉烯族真菌毒素，由多种镰刀菌在谷物中产生。T-2 毒素已被证明对人类和动物的健康产生一系列毒性作用，如免疫抑制和致癌作用。先前的研究已经证明 T-2 毒素会引起鸡的肝毒性，但调节机制尚不清楚。在本研究中，我们评估了 T-2 毒素对肝细胞凋亡和自噬的毒性作用。将 120 只 1 日龄健康肉鸡随机分为 4 组，分别用不含 T-2 毒素、0.5mg/kg、1mg/kg 或 2mg/kg T-2 毒素的全价饲料饲养 21 天。结果表明，随着 T-2 毒素的增加，肝细胞的凋亡率和病变程度加重。在分子机制水平上，T-2 毒素通过产生活性氧、促进细胞色素 c 在线粒体和细胞质之间的转移，从而促进凋亡小体的形成，诱导线粒体介导的细胞凋亡。同时，自噬相关蛋白 ATG5、ATG7 和 Beclin-1 的表达以及 LC3-II/LC3-I 比值增加，而 p62 下调，提示 T-2 毒素引起肝细胞自噬。进一步的实验表明，PI3K/AKT/mTOR 信号可能参与了 T-2 毒素诱导鸡肝细胞自噬的过程。这些数据表明，T-2 毒素诱导鸡肝细胞凋亡和自噬可能存在潜在的分子机制。
