CMZ Reversed Chronic Ethanol-Induced Disturbance of PPAR-α Possibly by Suppressing Oxidative Stress and PGC-1α Acetylation, and Activating the MAPK and GSK3β Pathway

摘要: Background Cytochrome P4502E1 (CYP2E1) has been suggested to play critical roles in the pathogenesis of alcoholic fatty liver (AFL), but underlying mechanisms remains unclear. The current study was designed evaluate whether CYP2E1 suppression by chlormethiazole (CMZ) could suppress AFL mice, and explore mechanisms. Methods Mice were treated with or without CMZ (50 mg/kg bw, i.p.) subjected liquid diet ethanol (5%, w/v) for 4 weeks. Biochemical parameters measured using commercial kits. protein mRNA levels detected western blot qPCR, respectively. Histopathology immunohistochemical assay performed routine methods. Results CYP2E1 inhibition completely blocked shown as decline hepatic serum triglyceride levels, fewer fat droplets sections. Chronic exposure led significant decrease peroxisome proliferator-activated receptor α (PPAR-α), which co-treatment. co-treatment suppressed ethanol-induced oxidative stress, overproduction tumor necrosis (TNF-α), PPAR-α co-activators including p300 deacetylated PGC1-α. Furthermore, activation AMP-activated kinase (AMPK), mitogen-activated (MAPK), PI3K/Akt/GSK3β pathway. However, chronic acyl-CoA carboxylase (ACC) acid synthase (FAS) partially restored CMZ, while autophagy appeared be CMZ. Conclusion These results that TNF-α overproduction, level deacetylation PGC1-α, activated AMPK, MAPK, pathway, might contribute account protection against AFL.