The Effects of Gabexate Mesilate on the Ishemia-Reperfusion Injury in the Rabbit Liver

ABSTRACT

PURPOSE: Ischemia-reperfusion is an important pathologic process that leads to impairment of the liver after major surgery. Ischmia-reperfusion injury includes both hypoxia and an inflammatory response associated with reperfusion; the former is caused by the lack of microvascular perfusion and the latter is mediated by cytyokines and oxygen free radicals. In addition to inhibiting thrombin, plasmin, kalikrein, trypsin, and neutrophil elastase, gabexate mesilate also plays an important role in inhibiting cytokines and oxygen free radical production. The purpose of this study was to investigate the effects of gabexate mesilate on ischemia- reperfusion injury in the liver. METHODS: Twenty-four New Zealand white rabbits were divided into three groups. Clamping was not done in group A (n=8), although it was done in group B (n=8) and group C (n=8). Group C received intravenous infusion of gabexate mesilate (10 mg/kg/hr) continuously during the process of clamping. Serum alanine aminotrasferase (ALT) and purine nucleoside phophorylase (PNP) were measured immediately before clamping, following 30-minute ischemia, and after 60-minute reperfusion. Hepatic tissue adenosine triphophate (ATP), xanthine oxidase, and malondialdehyde (MDA) plus 4-hydroxyalcenals (4HA) were measured after reperfusion. RESULTS: Compared with group A, group B and group C demonstrated a significant increase in ALT and PNP levels following ischemia and reperfusion, as well as in xanthine oxidase and MDA plus 4HA levels following reperfusion. However, ATP levels showed no significant differences among the three groups. ALT levels were significantly lower in group C than in group B following reperfusion (P<0.01),although there was no significant differences in PNP levels between them. Xanthine oxidase and MDA plus 4HA levels were significantly lower in group C than in group B (P<0.05). The results suggest that gabexate mesilate inhibits an increase in ALT, xanthine oxidase, and MDA plus 4HA levels. CONCLUSION: Gabexate mesilate inhibits oxygen free radical production of xanthine oxidase, and results in a reduction of hepatic ischemia-reperfusion injury.