c-jun N-terminal kinase activation during warm hepatic ischemia/reperfusion injuries in a rat model

Ischemia/reperfusion injuries are a major problem in liver resections and transplantations. Tumor necrosis factor-α has been widely investigated as a key mediator in the mechanism of ischemia/reperfusion injury. Upstream signal transduction mechanisms for tumor necrosis factor-α have not been well documented. Therefore, we assessed c-Jun N-terminal kinase activation during warm hepatic ischemia/reperfusion injuries in a rat model. Male Wistar rats were subjected to 30 minutes of ischemia followed by reperfusion. Hepatic enzymes, histological examinations, microfluorographs, and tumor necrosis factor-α protein production (in the serum and liver tissue) were analyzed during the course of reperfusion. c-Jun N-terminal kinase activity was measured by a radioisotope kinase assay. Ischemia/reperfusion injuries were characterized by an elevation in hepatic enzyme, the histological degeneration of hepatocytes, and an increase in the number of nonviable cells. Moreover, increased endothelial-adherent leukocytes and tumor necrosis factor-α protein production were also observed. c-Jun N-terminal kinase activity at 60 minutes after reperfusion was 12.4 times higher than the pre-ischemia level. These results suggest that c-Jun N-terminal kinase may play some role in the mechanism of ischemia/reperfusion injuries. (WOUND REP REG 2002;10:314–319)