The Effect of Pirfenidone on Immunological Liver and Lung Injury Induced by BCG in Female Balb/C Mice

Abstract

Background: BCG infection has been proven to induce immune hepatic and pulmonary injury in rodent animal with subsequent fibrosis development. Pirfenidone is an orally available pyridone derivative that proven to have antiinflammatory and anti-fibrotic effects in chemically and bile duct ligation induced fibrosis. Aim: The present study was undertaken to explore the potential protective effect of pirfenidone (500mg/kg/day, via gastric gavage) when coadministrated with BCG in an immunological model of liver and lung fibrosis. Methods: 18 female Balb/C mice were randomly divided into 3 groups (6 mice/each group); control group, BCG group and BCG+ pirfenidone treated group. All the animals were sacrificed on the 21th day of experiment. Liver function tests were performed by measuring serum; aspartate aminotransferase (AST), alanine aminotransferase (ALT). Hepatic and pulmonary tissues were removed for measuring; hepatic and pulmonary TNFα (tumor necrosis factor alpha), TGFβ (transforming growth factor beta), hydroxyproline and for histopathological examination. Abstract 115 Results: Mice injected by BCG exhibited a significant increase in the serum AST, ALT, hepatic and pulmonary TNFα, TGFβ and hydroxyproline compared to control group. Concomitant adminsitration of pirfenidone with BCG produced a significant decrease in serum AST, ALT, hepatic and pulmonary TNFα, TGFβ and hydroxyproline compared to BCG group. Along with improvement of hepatic and pulmonary histopathological changes that followed BCG in the form of restoration of normal hepatic and pulmonary architecture, apparent decrease in inflammatory cellular infiltration and significant decrease of hepatic and pulmonary percentage area of collagen fibers deposition. Conclusion: Pirfenidone has anti-inflammatory and antifibrotic effects in an immune hepatic and pulmonary injury model of induced by BCG in female Balb/C mice, and may represent a new therapeutic strategy for liver and lung fibrosis that needs further clinical evaluation. - Key words: Pirfenidone, Hepatic fibrosis, Pulmonary fibrosis, BCG.