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

Jung, Sung Eun; Yun, Ik Jin; Youn, Yeo Kyu; Lee, Joon Eui; Ha, Jongwon; Noh, Dong Young; Lee, Kun Kuk; Kim, Sang Joon; Oh, Seung Keun; Choe, Kuk Jin

Abstract

BACKGROUND: Liver failure due to ischemia-reperfusion injury is a serious problem in liver transplantation and radical wide resection of the liver. This injury is believed to be closely related to the generation of oxygen free radicals. Gabexate mesilate, a synthetic protease inhibitor, has an effect on the suppression of extracellular release of oxygen free radicals in the microvascular endothelium, as well as on protease inhibition. In order to understand the effects of gabexate mesilate on ischemia-reperfusion injury to the liver, we performed animal experiment with rats.
METHODS
We divided the rats into two ischemia-reperfusion groups:the experimental group which received a 30 minutes ischemic injury along with the infusion of gabexate mesilate and a control group which received only the injury. Each group was subdivided into 4 sub-groups:ischemic injury only and ischemic injury plus 60, 120 or 180 minutes reperfusion injury. The test parameters were TNF-a and IL-6 in the serum, and superoxide dismutase(SOD), catalase, and malondialdehyde(MDA) in liver and lung tissues.
RESULTS
The group receiving gabexate mesilate had a significantly higher level of liver SOD and liver catalase and a significantly lower level of liver MDA and lung MDA than the control groups. The TNF-a levels in the gabexate mesilate groups were significantly lower in the early phase, and a comparison of the IL-6 levels between two main groups yielded no significant results. The levels of lung catalase and SOD showed no significant difference between the two main groups.
CONCLUSIONS
Protease inhibitor has the beneficial effect of liver ischemia-reperfusion injury suppression due to an increase in antioxidants or oxygen-free-radical suppression. The roles of TNF-a and IL-6 in liver reperfusion injury was not clear in our investigation. However, TNF-a might have an effect in the early phase. The mechanism of reperfusion injury to the lung in liver ischemia-reperfusion injury might be different from that to the liver.