Abstract：
Deoxynivalenol (DON) is by far the most common mycotoxin contaminating cereal foods and feeds. Furthermore, cleaning up DON from contaminated cereal items is challenging. Low-dose DON consumption poses a danger to humans and agricultural animals. The benefits of hesperidin (HDN) include liver protection, anti-oxidative stress, nontoxicity, and a broad range of sources. The study used immunoblotting, immunofluorescence, and transmission electron microscopy to identify factors associated with mitophagy in vitro and in vivo. We demonstrated that low-dose DON exposure inhibited mitophagy in the liver tissue of mice. SIRT1 was a crucial regulator of mitophagy. Moreover, DON stimulated the dephosphorylation of SIRT1 and the acetylation-regulated FOXO3 protein, which resulted in the transcriptional inhibition of FOXO3-driven BNIP3 and compromised the stability of the PINK1 protein mediated by BNIP3. Moreover, HDN\'s effect was comparable to that of a SIRT1 agonist, which led to a significant decrease in the level of mitophagy inhibition caused by low-dose DON exposure. When combined, these findings suggested that HDN might be a useful treatment approach for liver damage brought on by low-dose DON exposure. Above all, this research will offer fresh perspectives on a viable approach that will encourage further research into risk reduction initiatives for low-dose DON exposure.
摘要：
脱氧雪腐镰刀菌烯醇（DON）是迄今为止最常见的霉菌毒素污染谷物食品和饲料。此外，从受污染的谷物物品中清除DON是一项挑战。低剂量DON消费对人类和农业动物构成危险。橙皮苷（HDN）的好处包括肝脏保护，抗氧化应激，无毒，和广泛的来源。这项研究使用了免疫印迹，免疫荧光，和透射电镜在体外和体内鉴定与线粒体自噬相关的因素。我们证明低剂量DON暴露抑制小鼠肝组织中的线粒体自噬。SIRT1是线粒体自噬的关键调节因子。此外，DON刺激SIRT1和乙酰化调节的FOXO3蛋白的去磷酸化，这导致FOXO3驱动的BNIP3的转录抑制，并损害了BNIP3介导的PINK1蛋白的稳定性。此外，HDN的效果与SIRT1激动剂相当，这导致低剂量DON暴露引起的线粒体自噬抑制水平显着降低。当组合时，这些研究结果表明,HDN可能是治疗低剂量DON所致肝损伤的有效方法.最重要的是,这项研究将为一种可行的方法提供新的观点，该方法将鼓励进一步研究低剂量DON暴露的风险降低措施。
