College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P.R. China.
Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, Northeast Agricultural University, Harbin 150030, P.R. China.
J Agric Food Chem. 2024 Oct 23;72(42):23511-23519. doi: 10.1021/acs.jafc.4c07006. Epub 2024 Oct 9.
Atrazine (ATZ), a widely used herbicide, disrupts mitochondrial function and lipid metabolism in the liver. Melatonin (MLT), a naturally synthesized hormone, combats mitochondrial dysfunction and alleviates lipid toxicity. However, the mechanisms behind ATZ-induced lipid metabolism toxicity and the protective effects of MLT remain unexplored. Mice were randomly assigned to four groups: control (Con), 5 mg/kg MLT, 170 mg/kg ATZ, and a cotreatment group receiving 170 mg/kg ATZ with 5 mg/kg MLT (ATZ+MLT). Additionally, we analyzed the effects of MLT and Rab8a on mRNA and proteins related to mitochondrial function and lipid metabolism disrupted by ATZ in AML12 cells. In conclusion, ATZ induced mitochondrial stress and disrupted fatty acid metabolism in mouse hepatocytes and AML12 cells. Exogenous MLT restores Rab8a levels, regulating fatty acid utilization in mitochondria and mitochondrial function. Notably, targeting Rab8a does not significantly affect mitochondrial function but prevents ATZ-induced lipid metabolism disorders in hepatocytes.
莠去津（ATZ）是一种广泛使用的除草剂，会破坏肝脏中的线粒体功能和脂质代谢。褪黑素（MLT）是一种天然合成的激素，可对抗线粒体功能障碍并减轻脂质毒性。然而，莠去津诱导的脂质代谢毒性的机制以及 MLT 的保护作用仍未得到探索。将小鼠随机分为四组：对照组（Con）、5mg/kg MLT 组、170mg/kg ATZ 组和接受 170mg/kg ATZ 加 5mg/kg MLT（ATZ+MLT）治疗的共处理组。此外，我们还分析了 MLT 和 Rab8a 对 AML12 细胞中由 ATZ 破坏的与线粒体功能和脂质代谢相关的 mRNA 和蛋白质的影响。总之，ATZ 诱导了小鼠肝细胞和 AML12 细胞中的线粒体应激和脂肪酸代谢紊乱。外源性 MLT 恢复了 Rab8a 水平，调节了线粒体中脂肪酸的利用和线粒体功能。值得注意的是，靶向 Rab8a 不会显著影响线粒体功能，但可预防 ATZ 诱导的肝细胞脂质代谢紊乱。
