Concomitant administration of atorvastatin with N-acetylcysteine mitigates liver injury and steatosis in experimental non-alcoholic fatty liver disease

Abstract

Although numerous efforts have been directed toward searching for new treatments against non-alcoholic fatty liver disease (NAFLD), there are no approved pharmacologic agents up to date. This study evaluates the therapeutic effect of concomitant administration of atorvastatin (ATO) and N-Acetylcysteine (NAC) with/without diet control. Nine groups of rats were divided into: normal, rats fed on high-fat diet for 12 weeks (NAFLD-HFD model), HFD-rats switched to regular diet (NAFLD-RD model), NAFLD-HFD or -RD rats treated with either ATO or NAC orally with 30 or 500 mg/kg/day, respectively, or both for 8 weeks. NAFLD-HFD rats exhibited remarkable steatosis with lobular inflammation, hepatocytes vacuolation, and fibrosis, as well as significant changes in lipid profile, oxidative stress, and adipocytokines and these manifestations were less prominent in the HFD-RD group. ATO and NAC combination with diet control has the added benefits on ameliorating lipid levels, liver enzymes, oxidative stress, hepatic steatosis (9.01% ± 1.66% vs. 13.21% ± 2.20% for ATO and 25.60% ± 2.11% for NAC), inflammation, hepatocyte vacuolation, and fibrosis versus each drug separately. Conclusion: ATO and NAC concomitant therapy has a greater effect on NAFLD as compared to monotherapy and is recommended for further investigation in clinical trials.