Resveratrol inhibits dimethylnitrosamine-induced hepatic fibrosis in rats.
Resveratrol, a phytoalexin found in grapes and red wines, has been reported to exhibit a wide range of pharmacological properties. In this study, we investigated the protective effect of resveratrol on hepatic injury induced by dimethylnitrosamine (DMN) in rats. Oral administration of resveratrol (20 mg/kg daily for 4 weeks) remarkably prevented the DMN-induced loss in body and liver weight, and inhibited the elevation of serum alanine transaminase, aspartate transaminase, alkaline phosphatase and bilirubin levels. Resveratrol also increased serum albumin and hepatic glutathione levels and reduced the hepatic level of malondialdehyde due to its antioxidant effect. Furthermore, DMN-induced elevation of hydroxyproline content was reduced in the resveratrol treated rats, the result of which was consistent with the reduction in type I collagen mRNA expression and the histological analysis of liver tissue stained with Sirius red. The reduction in hepatic stellate cell activation, as assessed by alpha-smooth muscle actin staining, and the reduction in transforming growth factor-beta1 mRNA expression were associated with resveratrol treatment. In conclusion, resveratrol exhibited in vivo hepatoprotective and antifibrogenic effects against DMN-induced liver injury, suggesting that resveratrol may be useful in the prevention of the development of hepatic fibrosis.
Lee
Eun-Sil
ES
College of Pharmacy, Pusan National University, Busan, Korea.
Shin
Mi-Ok
MO
Yoon
Sik
S
Moon
Jeon-Ok
JO
D000477:Alkylating Agents / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D056487:Chemical and Drug Induced Liver Injury, Chronic / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D004128:Dimethylnitrosamine / Q000633:toxicity*; D015536:Down-Regulation / Q000187:drug effects; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology / Q000627:therapeutic use*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D015431:Weight Loss / Q000187:drug effects
D000477:Alkylating Agents; D000975:Antioxidants; D015415:Biomarkers; D020011:Protective Agents; D012333:RNA, Messenger; D013267:Stilbenes; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; D004128:Dimethylnitrosamine; D000077185:Resveratrol