Resveratrol inhibits dimethylnitrosamine-induced hepatic fibrosis in rats
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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 α-smooth muscle actin staining, and the reduction in transforming growth factor-β1 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.
Key wordsResveratrol Hepatoprotective effect Antifibrogenic effect Antioxidant effect Hepatic stellate cell TGF-β1
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- Chávez, E., Reyes-Gordillo, K., Segovia, J., Shibayama, M., Tsutsumi, V., Vergara, P., Moreno, M. G., and Muriel, P., Resveratrol prevents fibrosis, NF-kappaB activation and TGF-beta increases induced by chronic CCl4 treatment in rats. J. Appl. Toxicol., 28, 35–43 (2008).CrossRefPubMedGoogle Scholar
- Gasso, M., Rubio, M., Varela, G., Cabre, M., Caballeria, J., Alonso, E., Deulofem, R., Camps, J., Gimene, Z, A., Piares, M., Pares, A., Mato, J. M., and Rodes, J., Effects of S-adenosylmethionine on lipid peroxidation and liver fibrogenesis in carbon tetrachloride-induced cirrhosis. J. Hepatol., 25, 200–205 (1996).CrossRefPubMedGoogle Scholar
- George, J., Roulot, D., Koteliansky, V. E., and Bissell, D. M., In vivo inhibition of rat stellate cell activation by soluble transforming growth factor beta type II receptor: a potential new therapy for hepatic fibrosis. Proc. Natl. Acad. Sci. U.S.A., 96, 12719–12724 (1999).CrossRefPubMedGoogle Scholar
- Godichaud, S., Si-Tayeb, K., Auge, N,. Desmouliere, A., Balabaud, C., Payrastre, B., Negre-Salvayre, A., and Rosenbaum, J., The grape-derived polyphenol resveratrol differentially affects epidermal and platelet-derived growth factor signaling in human liver myofibroblasts. Int. J. Biochem. Cell Biol., 38, 629–637 (2006).CrossRefPubMedGoogle Scholar
- Kolios, G., Valatas. V., and Kouroumalis E., Role of Kupffer cells in the pathogenesis of liver disease. World J. Gastroenterol., 14, 7413–7420 (2006).Google Scholar
- Parola, M., Pinzani, M., Casini, A., Albano, E., Poli, G., Gentilini, A., Gentilini, P., and Dianzani, M. U., Stimulation of lipid peroxidation or 4-hydroxynonenal treatment increases procollagen alpha 1 (I) gene expression in human liver fatstoring cells. Biochem. Biophys. Res. Commun., 194, 1044–1050 (1993).CrossRefPubMedGoogle Scholar
- Vendemiale, G., Grattagliano, I., Caruso, M. L., Serviddio, G., Valentini, A. M., Pirrelli, M., and Altomare, E., Increased oxidative stress in dimethylnitrosamine-induced liver fibrosis in the rat: effect of N-acetylcysteine and interferon-alpha. Toxicol. Appl. Pharmacol., 175, 130–139 (2001).CrossRefPubMedGoogle Scholar