Exercise training and Silymarin consumption can ameliorate mitophagy signaling flux in hepatocytes of rats with dexamethasone-induced non-alcoholic fatty liver disease.

This study aimed to investigate the effects of exercise training combined with silymarin supplementation on mitophagy markers in hepatocytes of rats with dexamethasone-induced non-alcoholic fatty liver disease (NAFLD). Forty-two male Wistar rats (6 weeks old) were divided into 7 groups (n = 6 per group): 1- Control (CON), 2- Dexamethasone (DEX), 3- DEX + moderate-intensity training (DEX-MIT), 4- DEX + high intensity training (DEX-HIT), 5- DEX + silymarin (DEX-S), 6- DEX + moderate intensity training + silymarin (DEX-MIT-S), 7- DEX-high intensity training + silymarin (DEX-HIT-S). NAFLD was induced by subcutaneous administration of dexamethasone for 7 days. Exercise groups underwent 8 weeks of treadmill running (5 sessions/week) at matched distances for MIT and HIT protocols. Silymarin was administered via oral gavage at a dose of 300 mg/kg body weight/day. Gene expression levels of mTORC1, AMPKα2, Bcl-2, Parkin, and LC3 were measured using real-time PCR. Protein levels of PINK1, Beclin-1, and P62 were assessed by western blotting. Moderate and high intensity training significantly reduced Bcl-2 and LC3 gene expression and increased P62 protein levels compared to the DEX group (P < 0.05). Silymarin supplementation significantly decreased expression of Parkin, Bcl-2, LC3, and PINK1 compared to the DEX (P < 0.05). Bcl-2 and LC3 gene expressions were lower in DEX-MIT-S and DEX-HIT-S compared to DEX (P < 0.05). PINK1 levels were reduced in the DEX-MIT-S relative to DEX (P < 0.05). LC3 gene expression was higher in DEX-HIT-S compared to DEX-MIT-S (P < 0.05). The findings suggest that both exercise training and silymarin supplementation can attenuate excessive mitophagy signaling in hepatocytes of rats with dexamethasone-induced NAFLD, potentially providing hepatoprotective effects against further damage.