Effect of Protease Inhibitor on Ischemia-reperfusion Injury to Rat Liver

Abstract.

Liver failure due to ischemia-reperfusion injury, believed to be closely related to the generation of oxygen-free radicals, is a serious problem during liver surgery. Gabexate mesilate, a synthetic protease inhibitor, suppresses the extracellular release of oxygen-free radicals in the microvascular endothelium. To determine its effects on ischemia-reperfusion injury to the liver, we performed experiments with rats. We divided the animals into two ischemia-reperfusion groups: an experimental group, which underwent ischemic injury for 30 minutes, along with the infusion of gabexate mesilate, and a control group, which underwent injury only. Each group was then divided into four subgroups: ischemic injury only and 60-, 120-, and 180-minute reperfusion injury. The test parameters were tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) in serum and superoxide dismutase (SOD), catalase, and malondialdehyde (MDA) in liver and lung tissues. The experimental group had a significantly higher liver SOD and catalase levels and a significantly lower level of liver and lung MDA than the control groups. TNFα levels in the experimental groups were significantly lower during the early phase, but a comparison of IL-6 levels between the two groups yielded no differences. Levels of lung catalase and SOD were not significantly different between the two groups. We concluded that protease inhibitor suppressed liver ischemia-reperfusion injury, and that it was due to an increase of antioxidant or suppression of oxygen-free radicals. The roles of TNFα and IL-6 in liver reperfusion injury were not clear, though TNFα might have had an effect during the early phase. With liver ischemia-reperfusion injury, the mechanism of lung involvement might be different from that of liver involvement.