Aims: 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.
Main methods: 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.
Key findings: 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.
Significance: 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.
Keywords: Collagen, TGF-β; Concanavalin A (ConA); Extracellular matrix (ECM); Hepatic stellate cells (HSCs); Hydroxyprolline; Liver fibrosis; MMP-2; Pirfenidone (PFD); TIMP-1; TNF-α.
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