Journal
JOURNAL OF PHARMACY AND PHARMACOLOGY
Volume 68, Issue 12, Pages 1559-1566Publisher
WILEY-BLACKWELL
DOI: 10.1111/jphp.12651
Keywords
concanavalin A; hepatitis; nuclear factor kappa B; oxidative stress; pirfenidone
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ObjectivesThis study aimed to evaluate the potential protective effects of pirfenidone (PFD) against concanavalin A (Con A)-induced hepatitis in mice. MethodsAutoimmune 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 findingsHepatitis 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-B) expression and inflammatory cytokines levels (tumour necrosis factor-alpha, interleukin-6 and nitric oxide). PFD pretreatment potently ameliorated all these pathological changes. ConclusionsPirfenidone hepatoprotective activity may be mediated through its antioxidant ability that suppresses NF-B activation signalling pathways suggesting that PFD may be a new candidate for treatment of acute hepatitis.
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