The effects of thromboxane synthase inhibition on reperfusion injury and endothelin-1,2 levels in allograft kidney transplantation in rats

Thromboxane A(2) is a proaggregative vasoconstrictor that is synthesized an d released in reperfusion injury. We aimed to investigate the effects of th romboxane synthase inhibitor, UK 38485, on endothelin-1,2 (ET) response of the renal endothelium and lipid peroxidation and protein oxidation in the e arly period of kidney transplantation. Four groups (n = 8) of Sprague-Dawle y rats were designed as Group I (sham nephrectomy), Group II (autotransplan tation), Group III (allotransplantation) and Group IV (allotransplantation group in which the allografts were perfused with UK 38485. All subjects und erwent right nephrectomy after transplantation. The grafts were flushed wit h 4 mi of ice-cold Ringer's lactate and in Group TV 10 mu g of UK 38485 was added into the solution for each kidney. In allotransplantation groups, th e kidneys were harvested from allogeneic white Wistar albino rats. The kidn ey grafts were allowed 120 min of reperfusion after 40 min of cold ischemic period. ET-1,2 plasma concentrations in the renal vein blood and diene con jugates (DC), hydroxyalkanals (HAA), hydroxyalkenals (HAE) and malondialdeh yde (MDA) levels as the products of lipid peroxidation, protein carbonyls a nd protein sulfhydryls as the indicators of protein oxidation were analyzed in kidney tissue. Plasma ET-1,2 concentrations increased significantly in Group II and Group III(P<0.01) when compared to Group I but decreased in Gr oup IV in comparison with Group III (P<0.05). DC, HAA, HAE and MDA levels i ncreased in Groups II and III (P<0.001). Significant protein oxidation occu rred only in Group III (P<0.01). Perfusion of the allografts with UK 38485 prevented lipid peroxidation and protein oxidation in Group IV. Histopathol ogical changes were mild in the last group. We concluded that, in kidney tr ansplantation, local administration of UK 38485 has cytopreservative effect s on the allografts and this effect can be related to ET-1,2 concentrations .