Rab8a Is a Key\nTarget That Melatonin Prevents Lipid\nDisorder from Atrazine

Atrazine\n(ATZ), a widely used herbicide, disrupts mitochondrial\nfunction and lipid metabolism in the liver. Melatonin (MLT), a naturally\nsynthesized hormone, combats mitochondrial dysfunction and alleviates\nlipid toxicity. However, the mechanisms behind ATZ-induced lipid metabolism\ntoxicity and the protective effects of MLT remain unexplored. Mice\nwere randomly assigned to four groups: control (Con), 5 mg/kg MLT,\n170 mg/kg ATZ, and a cotreatment group receiving 170 mg/kg ATZ with\n5 mg/kg MLT (ATZ+MLT). Additionally, we analyzed the effects of MLT\nand Rab8a on mRNA and proteins related to mitochondrial function and\nlipid metabolism disrupted by ATZ in AML12 cells. In conclusion, ATZ\ninduced mitochondrial stress and disrupted fatty acid metabolism in\nmouse hepatocytes and AML12 cells. Exogenous MLT restores Rab8a levels,\nregulating fatty acid utilization in mitochondria and mitochondrial\nfunction. Notably, targeting Rab8a does not significantly affect mitochondrial\nfunction but prevents ATZ-induced lipid metabolism disorders in hepatocytes.