Prednisolone suppresses ischemia-reperfusion injury of the rat liver by reducing cytokine production and calpain μ activation

Background: We investigated the effects of prednisolone on cytokine production and calpain μ activation during hepatic ischemia-reperfusion (IR) injury. Methods: The hilar area of the left lateral and median lobes of rat liver was clamped for 60 min. Prednisolone was administered at 1.0, 3.0, or 10 mg/kg at 30 min before ischemia. In addition to biochemical and microscopic analyses, IL-β and TNF-α production was evaluated by RT-PCR. Calpain μ activation and talin degradation were determined by Western blotting, using specific antibodies. Results: In the control and prednisolone (1.0 mg/kg) groups, serum AST and ALT levels were elevated, and cell membrane bleb formation was observed after 2 h of reperfusion. Moreover, calpain μ activation, talin degradation, and overexpression of IL-β and TNF-α mRNAs were detected. Infusion of prednisolone at 3.0 or 10 mg/kg significantly suppressed biochemical and microscopic changes. At 10 mg/kg, prednisolone markedly suppressed IL-β and TNF-α transcription and calpain μ activation and talin degradation, consistent with the improved 7-day survival after total hepatic ischemia (75% vs. 25% in control group, P=0.039). Conclusions: Cytoprotective effect of prednisolone in hepatic IR injury was closely associated with suppression of IL-β/TNF-α production and calpain μ activation.