Abstract：
Deoxynivalenol (DON) is a common agricultural mycotoxin that is chemically stable and not easily removed from cereal foods. When organisms consume food made from contaminated crops, it can be hazardous to their health. Numerous studies in recent years have found that hesperidin (HDN) has hepatoprotective effects on a wide range of toxins. However, few scholars have explored the potential of HDN in attenuating DON-induced liver injury. In this study, we established a low-dose DON exposure model and intervened with three doses of HDN, acting on male C57 BL/6 mice and AML12 cells, which served as in vivo and in vitro models, respectively, to investigate the protective mechanism of HDN against DON exposure-induced liver injury. The results suggested that DON disrupted hepatic autophagic fluxes, thereby impairing liver structure and function, and HDN significantly attenuated these changes. Further studies revealed that HDN alleviated DON-induced excessive autophagy through the mTOR pathway and DON-induced lysosomal dysfunction through the AKT/GSK3β/TFEB pathway. Overall, our study suggested that HDN could ameliorate DON-induced autophagy flux disorders via the mTOR pathway and the AKT/GSK3β/TFEB pathway, thereby reducing liver injury.
摘要：
脱氧雪腐镰刀菌烯醇（DON）是一种常见的农业霉菌毒素，化学稳定，不易从谷物食品中去除。当生物体消耗由被污染的作物制成的食物时，这可能对他们的健康有害。近年来大量研究发现橙皮苷(HDN)对多种毒素具有保肝作用。然而,很少有学者探讨HDN在减轻DON诱导的肝损伤中的潜力。在这项研究中,我们建立了低剂量DON暴露模型，并采用三种剂量的HDN进行干预，作用于雄性C57BL/6小鼠和AML12细胞，作为体内和体外模型，分别,探讨HDN对DON暴露所致肝损伤的保护机制。结果表明，DON破坏了肝脏自噬通量，从而损害肝脏结构和功能，和HDN显著减弱这些变化。进一步的研究表明，HDN通过mTOR途径减轻DON诱导的过度自噬，并通过AKT/GSK3β/TFEB途径减轻DON诱导的溶酶体功能障碍。总的来说,我们的研究表明，HDN可以通过mTOR途径和AKT/GSK3β/TFEB途径改善DON诱导的自噬通量障碍，从而减少肝损伤。
