Resveratrol inhibits dimethylnitrosamine-induced hepatic fibrosis in rats

Abstract

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.

Effect of dietary supplementation of grape skin and seeds on liver fibrosis induced by dimethylnitrosamine in rats

“…Among those phytochemicals, high levels of resveratrol mainly exist in the skin of grape and proanthocyanidins exist in the seed of grape. Resveratrol is reported that it has the antifibrotic effects in rat fibrosis model by CCl 4 [25] and DMN [26]. Proanthocyanidins are antifibrotic in experimental biliary obstruction [27] and in the DMN-induced fibrosis model [28] in rats.…”

Protective Effects of Ethyl Acetate Soluble Fraction of <i>Limonium tetragonum</i> on Diethylnitrosamine-Induced Liver Fibrosis in Rats

“…2) Oxidative stress stimulates proliferation and invasiveness of HSCs and plant-derived antioxidants such as curcumin and resveratrol reduce HSC activation, thus suppressing liver fibrosis. [3][4][5] Animal models to investigate the potential hepatoprotective drugs that suppress liver fibrosis have been well defined. 6) Carbon tetrachloride (CCl 4 ), thioacetamide (TAA), dimethylnitrosamine or diethylnitrosamine (DMN or DEN) are considered as the most common hepatotoxic agents in experimental models.…”

Resveratrol: Is It Really Good for Liver Health?

“…In 1 study, the oral administration of RES at 20 mg/kg daily for 4 weeks in rats prevented diethylnitrosamine (DEN)-induced body and liver weight loss, inhibited the elevation of serum parameter associated with the liver insult (eg, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), bilirubin), and reduced activation of hepatic stellate cells (HSC) and collagen expression (9). Similar results were obtained when rats were treated with higher RES concentrations (40 mg/kg) for shorter time periods (7 days) (10).…”