Wang Yihan, Fu Jiali, Zhou Danni, Ren Zhihua, Deng Junliang
Sichuan Agricultural University, College of Veterinary Medicine, Chengdu, China.
Henan Agricultural University, College of Veterinary Medicine, Zhengzhou, China.
Mycotoxin Res. 2025 Jul 16. doi: 10.1007/s12550-025-00601-5.
Deoxynivalenol (DON)-induced liver injury is closely associated with mitochondrial dysfunction, yet it remains unclear whether this injury is mediated by mitochondrial autophagy via the PGC-1α/SIRT3 pathway. This study aimed to ascertain whether DON triggers mitochondrial autophagy, thereby causing liver injury in mice through the PGC-1α/SIRT3 pathway. Mice were orally administered DON at doses of 1.2 and 2.4 mg/kg once daily for 28 consecutive days. The results indicated that DON treatment significantly elevated the activity levels of two key liver enzymes and increased oxidative stress in the mouse liver. Additionally, DON upregulated several pivotal pro-inflammatory cytokines in the liver, leading to inflammation. The impact of DON on liver mitochondrial autophagy was assessed through histopathological analysis and observations of mitochondrial ultrastructure. These alterations were concurrent with activating the PGC-1α/SIRT3 signaling pathway in the liver following DON exposure. This research demonstrates that PGC-1α/SIRT3-regulated mitochondrial autophagy exacerbates DON-related hepatic damage, shedding light on the molecular mechanisms involved.
脱氧雪腐镰刀菌烯醇（DON）诱导的肝损伤与线粒体功能障碍密切相关，但尚不清楚这种损伤是否通过PGC-1α/SIRT3途径由线粒体自噬介导。本研究旨在确定DON是否触发线粒体自噬，从而通过PGC-1α/SIRT3途径导致小鼠肝损伤。小鼠连续28天每天口服剂量为1.2和2.4mg/kg的DON。结果表明，DON处理显著提高了两种关键肝酶的活性水平，并增加了小鼠肝脏的氧化应激。此外，DON上调了肝脏中几种关键的促炎细胞因子，导致炎症。通过组织病理学分析和线粒体超微结构观察评估DON对肝线粒体自噬的影响。这些改变与DON暴露后肝脏中PGC-1α/SIRT3信号通路的激活同时发生。本研究表明，PGC-1α/SIRT3调节的线粒体自噬加剧了DON相关的肝损伤，揭示了其中涉及的分子机制。
