stilbenes and Choline-Deficiency

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.. The objective of this study was to evaluate protective effects of RSV and NAC, compared with ursodeoxycholic acid (UDCA), on experimental NAFLD.. 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.. 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.. RSV and NAC are effective on NAFLD through antioxidant, anti-inflammatory, and lipid-lowering potentials, where as RSV seems better than UDCA or NAC.

Topics: Acetylcysteine; Animals; Antioxidants; Biomarkers; Choline Deficiency; Cytoprotection; Disease Models, Animal; Hypolipidemic Agents; Lipids; Liver; Male; Methionine; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Rats, Wistar; Resveratrol; Stilbenes; Ursodeoxycholic Acid

Non-alcoholic steatohepatitis (NASH) is one of the leading causes of chronic liver disease that can progress to liver fibrosis, cirrhosis and eventually hepatocellular carcinoma. Resveratrol, a naturally occurring phytoalexin, is believed to have therapeutic effects on hepatic steatosis. However, the effect of resveratrol on NASH and the underlying mechanism is not fully illustrated. In the present study, we aimed to exam the effect of resveratrol on methionine/choline-deficient (MCD) diet or medium-induced hepatic steatosis, oxidation and inflammation, and to explore the possible mechanism.. C57BL/6 mice and AML12 cells were treated with MCD alone or in combination with different concentrations of resveratrol (100 mg/kg/day or 250 mg/kg/day for mice and 25 μmol/L, 50 μmol/L, or 100 μmol/L for cells). Levels of aminotransferases (ALT), interleukin 1β (IL-1β), IL-6, and tumor necrosis factor alpha (TNF-α) were measured, concentrations of triglyceride (TG) and thiobarbituric acid reactive substances (TBARs) were determined, and expressions of proteins involved in autophagy were analyzed.. The results indicate that MCD diet or medium induced NASH in mouse and AML12 cell, which was confirmed by the elevated levels of TG, TNF-α, IL-1β, IL-6, ALT and TBARS in mice serum or cell culture medium. Resveratrol administration slowed down NASH progression, decreased the levels of ALT, TG, TBARS, IL-1β, IL-6, downregulated mRNA expressions of TNF-α, IL-1β, IL-6, and regulated the expressions of proteins involved in autophagy, both in vitro and in vivo. However, an autophagical inhibitor significantly impaired the protective role of resveratrol on liver injury and inflammation.. Resveratrol can attenuate hepatic steatosis and inflammation in MCD-induced NASH by regulating autophagy. Thus, resveratrol may be a promising agent for inhibiting lipid accumulation and inflammatory processes associated with NASH.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Autophagy; Choline Deficiency; Cytokines; Drug Evaluation, Preclinical; Gene Expression; Male; Methionine; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Resveratrol; Stilbenes