Protective effect of ursodeoxycholic acid, resveratrol, and N-acetylcysteine on nonalcoholic fatty liver disease in rats

Abstract

Context: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Resveratrol (RSV) and N-acetylcysteine (NAC) are safe representatives of natural and synthetic antioxidants, respectively. Objective: The objective of this study was to evaluate protective effects of RSV and NAC, compared with ursodeoxycholic acid (UDCA), on experimental NAFLD. Materials and methods: NAFLD was induced by feeding rats a methionine choline-deficient diet (MCDD) for four cycles, each of 4 d of MCDD feeding and 3 d of fasting. Animals were divided into normal control, steatosis control, and five treatment groups, receiving UDCA (25 mg/kg/d), RSV (10 mg/kg/d), NAC (20 mg/kg/d), UDCA + RSV, and UDCA + NAC orally for 28 d. Liver integrity markers (liver index and serum transaminases), serum tumor necrosis factor-α (TNF-α), glucose, albumin, renal functions (urea, creatinine), lipid profile (total cholesterol; TC, triglycerides, high density lipoproteins, low density lipoproteins; LDL-C, very low density lipoproteins, leptin), and oxidative stress markers (hepatic malondialdehyde; MDA, glutathione; GSH, glutathione-S-transferase; GST) were measured using automatic analyzer, colorimetric kits, and ELISA kits, supported by a liver histopathological study. Results: RSV and NAC administration significantly improved liver index (RSV only), alanine transaminase (52, 52%), TNF-α (70, 70%), glucose (69, 80%), albumin (122, 114%), MDA (55, 63%), GSH (160, 152%), GST (84, 84%), TC (86, 86%), LDL-C (83, 81%), and leptin (59, 70%) levels compared with steatosis control values. A combination of RSV or NAC with UDCA seems to ameliorate their effects. Discussion and conclusion: RSV and NAC are effective on NAFLD through antioxidant, anti-inflammatory, and lipid-lowering potentials, where as RSV seems better than UDCA or NAC.