Protective effects of pirfenidone on D-galactosamine and lipopolysaccharide-induced acute hepatotoxicity in rats

Objective: 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.