Potent antioxidant role of pirfenidone in experimental cirrhosis.

作者: Adriana Salazar-Montes , Luis Ruiz-Corro , Alberto López-Reyes , Eugenio Castrejón-Gómez , Juan Armendáriz-Borunda

DOI: 10.1016/J.EJPHAR.2008.06.110

关键词:

摘要: Three important features must be considered when proposing therapeutic strategies in liver cirrhosis: inflammation, oxidative stress and fibrogenesis. Pirfenidone is a synthetic molecule which action has not been tested cirrhosis. Cirrhosis was induced rats by ligation of the common bile duct or carbon tetrachloride (CCl(4)) chronic intoxication treated with pirfenidone diphenyleneiodonium (a potent known antioxidant) for last two weeks model three CCl(4) intoxication. A 60% reduction fibrosis index 42% along reduced inflammation observed. Considerable on hepatic enzymes total direct bilirubins were detected both models. antioxidant capacity rendered 28% 30% nitrites malonyldealdehide concentration 52% 38% CCl(4). With respect to gene expression, fibrotic genes like transforming growth factor-beta (TGF-beta) collagen Ialpha (Col-1alpha) down-regulated increased expression regenerative hepatocyte factor (HGF) c-met . Superoxide dismutase (SOD), catalase (CAT) inducible nitric oxide synthase (iNOS) importantly where nuclear kappa B (NF-kappaB) binding activity also decreased treatment. Also, SOD CAT functional after action. On other hand, drop similar extent pirfenidone, but it as effective reducing fibrosis. In this work, we showed properties beyond its well-known antifibrotic effect. These make an attractive drug trying diseases accompanied processes.

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