Pirfenidone ameliorates concanavalin A-induced hepatitis in mice via modulation of reactive oxygen species/nuclear factor kappa B signalling pathways

Abstract

Abstract Objectives This study aimed to evaluate the potential protective effects of pirfenidone (PFD) against concanavalin A (Con A)-induced hepatitis in mice. Methods Autoimmune model of hepatitis was established using single intravenous injection of Con A. Mice were randomly assigned into four groups as follows: control group; Con A group; and two groups, receiving PFD in two dose levels (200, 300 mg/kg) for 5 days before Con A administration. Extent of hepatitis was studied using biochemical, histopathological and immunohistochemical estimations. Key findings Hepatitis was clearly evident through extensive hepatocellular lesions and elevated levels of serum transaminases, alkaline phosphatase and lactate dehydrogenase. Con A induced an imbalance between oxidant and antioxidant status in the hepatic tissue. Furthermore, Con A significantly elevated hepatic nuclear factor kappa B (NF-κB) expression and inflammatory cytokines levels (tumour necrosis factor-alpha, interleukin-6 and nitric oxide). PFD pretreatment potently ameliorated all these pathological changes. Conclusions Pirfenidone hepatoprotective activity may be mediated through its antioxidant ability that suppresses NF-κB activation signalling pathways suggesting that PFD may be a new candidate for treatment of acute hepatitis.