Effect of Pirfenidone on Endotoxin-induced Liver Injury after Partial Hepatectomy in Rats

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Background. In living donor liver transplantation, restrictions on graft size are a serious obstacle for the expansion of indications for adult recipients. The sequence of gram-negative infection, septicemia, and multiple organ failure is the most common cause of early mortality after liver transplantation. An effective therapy is not still established in endotoxemia following extended hepatectomy in donor or small for size graft in recipient. Pirfenidone (PFD) is a new experimental drug used as an antifibrotic agent. We investigated the effect of PFD on endotoxin-induced liver injury following partial hepatectomy.Methods. Male Sprague-Dawley rats were intravenously administered with lipopolysaccharide (LPS) 48 h after 70% hepatectomy. Prior to LPS administration, PFD (300 mg/kg) or its vehicle (0.5% carboxymethylcellulose) was given orally twice.Results. The survival rate of the PFD-treated group was markedly improved as compared with that of controls. PFD prevented the increases in activities of serum enzymes (AST, ALT, LDH) and total bilirubin. The levels of inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β interferon-γ and interleukin-6 in serum and liver tissue were significantly lower in the PFD-treated group than in the control group. Furthermore, the degree of necrosis in remnant liver significantly decreased in the PFD-treated rats as compared with controls.Conclusion. These results indicate that PFD alleviates endotoxin-induced liver injury after partial hepatectomy through the inhibition of production of inflammatory cytokines in the remaining liver. PFD may be useful to prevent endotoxin-induced liver injury after hepatectomy.