F Wang1, T Wen, X-Y Chen, H Wu. 1. Department of Infectious Diseases, Beijing You-an Hospital affiliated with Capital Medical University, Beijing, 100069, PR China.
Abstract
OBJECTIVE AND DESIGN: To investigate the protective effects of pirfenidone on acute liver damage caused by D-galactosamine (GalN)/lipopolysaccharide (LPS) in rats. MATERIAL AND TREATMENT: Sprague-Dawley rats were divided into five groups (five rats per group): normal control group, GalN/LPS-treated group, and three pirfenidone-treated group (100, 300 and 500 mg/kg i.p., respectively). All biochemical and histological indexes were determined at 12 h after GalN/LPS challenge. METHODS: Severity of liver injury was assessed by determination of serum ALT, AST levels and histological analysis. SOD activity and MDA concentrations as well as TNF-alpha and IFN-gamma levels in the liver of rats were measured. The expression of iNOS and its product, NO concentration were also determined. RESULTS: Pretreatment with pirfenidone significantly attenuated GalN/LPS-induced severe hepatotoxicity, as evidenced by decreased ALT, AST levels and MDA content and improved histopathological changes. Pirfenidone inhibited the elevated levels of TNF-alpha and IFN-gamma and reduced the induction of iNOS/NO in a dose-dependent manner, which might be important mechanisms related to its protective effect. CONCLUSIONS: Pirfenidone can provide a definite protective effect against acute hepatic injury caused by GalN/LPS in rats, which may be mainly mediated through its anti-inflammatory effect.
OBJECTIVE AND DESIGN: To investigate the protective effects of pirfenidone on acute liver damage caused by D-galactosamine (GalN)/lipopolysaccharide (LPS) in rats. MATERIAL AND TREATMENT: Sprague-Dawley rats were divided into five groups (five rats per group): normal control group, GalN/LPS-treated group, and three pirfenidone-treated group (100, 300 and 500 mg/kg i.p., respectively). All biochemical and histological indexes were determined at 12 h after GalN/LPS challenge. METHODS: Severity of liver injury was assessed by determination of serum ALT, AST levels and histological analysis. SOD activity and MDA concentrations as well as TNF-alpha and IFN-gamma levels in the liver of rats were measured. The expression of iNOS and its product, NO concentration were also determined. RESULTS: Pretreatment with pirfenidone significantly attenuated GalN/LPS-induced severe hepatotoxicity, as evidenced by decreased ALT, AST levels and MDA content and improved histopathological changes. Pirfenidone inhibited the elevated levels of TNF-alpha and IFN-gamma and reduced the induction of iNOS/NO in a dose-dependent manner, which might be important mechanisms related to its protective effect. CONCLUSIONS:Pirfenidone can provide a definite protective effect against acute hepatic injury caused by GalN/LPS in rats, which may be mainly mediated through its anti-inflammatory effect.
Authors: José Macías-Barragán; Ana Sandoval-Rodríguez; Jose Navarro-Partida; Juan Armendáriz-Borunda Journal: Fibrogenesis Tissue Repair Date: 2010-09-01
Authors: David Alejandro Lopez-de la Mora; Cibeles Sanchez-Roque; Margarita Montoya-Buelna; Sergio Sanchez-Enriquez; Silvia Lucano-Landeros; Jose Macias-Barragan; Juan Armendariz-Borunda Journal: Int J Med Sci Date: 2015-10-14 Impact factor: 3.738