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

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.