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Resveratrol prevents fibrosis, NF‐ κ B activation and TGF‐ β increases induced by chronic CCl 4 treatment in rats
Author(s) -
Chávez Enrique,
ReyesGordillo Karina,
Segovia José,
Shibayama Mineko,
Tsutsumi Victor,
Vergara Paula,
Moreno Mario G.,
Muriel Pablo
Publication year - 2008
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.1249
Subject(s) - resveratrol , hydroxyproline , chemistry , fibrosis , antioxidant , pharmacology , alkaline phosphatase , endocrinology , medicine , biochemistry , enzyme
Resveratrol is a nonflavonoid polyphenol with antioxidant, anticancer and antiinflammatory properties. Moreover, it has been reported that this compound inhibits NF‐ κ B, which regulates the transcription of several genes including cytokines such as the profibrogenic TGF‐ β . The aim of this work was to evaluate the pharmacological effects of resveratrol on CCl 4 ‐induced cirrhosis in the rat. Four groups were formed: the control group that received the vehicles only; the CCl 4 group that received the toxin (0.4 g kg −1 , i.p., three times a week, for 8 weeks); the CCl 4 plus resveratrol (10 mg kg −1 , daily) group; and the resveratrol alone group. Alanine aminotransferase, alkaline phosphatase and bilirubins were increased by CCl 4 , but resveratrol afforded some degree of protection. Glycogen was decreased markedly by CCl 4 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 CCl 4 group; resveratrol preserved the content of collagen. These results were corroborated by histopathology. To elucidate the antifibrogenic mechanism of resveratrol, the activation of NF‐ κ B and the production of TGF‐ β were measured; in both cases CCl 4 increased them and resveratrol abolished them; however, changes in NF‐ κ B were modest and did not reach statistical significance, while the increase in TGF‐ β 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 CCl 4 model of cirrhosis. Moreover, the action mechanism is probably associated with its ability to reduce NF‐ κ B activation and TGF‐ β content. Copyright © 2007 John Wiley & Sons, Ltd.