concanavalin-a and pirfenidone

Liver fibrosis (LF) is a life-threatening complication of most chronic liver diseases resulting from a variety of injurious agents and hepatotoxic insults. To date, there are no specific therapies for LF, and all the currently available drugs have been developed for other indications. Thus, there is a pressing need to develop new drugs for treatment of LF. Therefore, the current study aimed to elucidate the potential antifibrotic effect of Pirfenidone (PFD) against concanavalin A (ConA)-induced immunological model of liver fibrosis in mice.. Hepatic fibrosis was induced in mice by injecting ConA (10 mg/kg/wk./i.v) for 4 weeks. Then, the mice were treated with or without PFD (125 mg/kg/ip/day) for 2 weeks. Hepatic fibrosis was determined by Masson Trichrome staining; Haematoxylin & eosin (H&E) staining, immunohistochemistry staining of type II and IV collagens, and colorimetric assessment of hydroxyprolline (HP) content in the liver tissues. In addition, the expression of α-SMA mRNA was determined by real time RT-PCR. The serum levels of TGF-β, TNF-α, TIMP-1 and MMP-2 were measured by ELISA.. Treatment with PFD significantly reduced ConA-induced expression of type II and IV collagens, α-SMA mRNA expression, and HP content and decreased inflammatory cells infiltration in hepatic tissues. Furthermore, serum levels of TGF-β, TNF-α, and TIMP-1 were significantly reduced with concomitant increase in MMP-2 expression.. Treatment with PFD ameliorates concanavalin A-induced hepatic inflammation and fibrosis in mice. Thus, PFD may represent a promising therapeutic option for hepatic fibrosis and its related complications.

Topics: Animals; Collagen Type II; Collagen Type IV; Concanavalin A; Disease Models, Animal; Hepatic Stellate Cells; Liver; Liver Cirrhosis; Male; Matrix Metalloproteinase 2; Mice; Mice, Inbred BALB C; Pyridones; RNA, Messenger; Tissue Inhibitor of Metalloproteinase-1; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

This study aimed to evaluate the potential protective effects of pirfenidone (PFD) against concanavalin A (Con A)-induced hepatitis in mice.. 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.. 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.. 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.

Topics: Animals; Antioxidants; Biomarkers; Chemical and Drug Induced Liver Injury; Concanavalin A; Cytoprotection; Disease Models, Animal; Hepatitis, Autoimmune; Liver; Male; Mice; NF-kappa B; Oxidative Stress; Pyridones; Reactive Oxygen Species; Signal Transduction