Resveratrol prevents fibrosis, NF-kappa B activation and TGF-beta increases induced by chronic CCl4 treatment in rats

Resveratrol is a nonflavonoid polyphenol with antioxidant, anticancer and antiinflammatory properties. Moreover, it has been reported that this compound inhibits NF-kappa B, which regulates the transcription of several genes including cytokines such as the profibrogenic TGF-beta. The aim of this work was to evaluate the pharmacological effects of resveratrol on CCl4-induced cirrhosis in the rat. Four groups were formed: the control group that received the vehicles only; the CCl4 group that received the toxin (0.4 g kg(-1), i.p., three times a week, for 8 weeks); the CCl4 plus resveratrol (10 mg kg(-1), daily) group; and the resveratrol alone group. Alanine aminotransferase, alkaline phosphatase and bilirubins were increased by CCl4, but resveratrol afforded some degree of protection. Glycogen was decreased markedly by CCl4 and resveratrol prevented almost completely this effect. No antioxidant effect of resveratrol was observed. One of the most prominent effects was on fibrosis which increased near 5-fold (hydroxyproline) in the CCl4 group; resveratrol preserved the content of collagen. These results were corroborated by histopathology. To elucidate the antifibrogenic mechanism of resveratrol, the activation of NF-kappa B and the production of TGF-beta were measured; in both cases CCl4 increased them and resveratrol abolished them; however, changes in NF-kappa B were modest and did not reach statistical significance, while the increase in TGF-beta was about three fold and resveratrol decreased it under control values. Together, the present results indicate that resveratrol possesses a strong antifibrogenic effect at least in the CCl4 model of cirrhosis. Moreover, the action mechanism is probably associated with its ability to reduce NF-kappa B activation and TGF-beta content. Copyright (C) 2007 John Wiley & Sons, Ltd.