Protective effects of thromboxane A2 synthetase inhibitor (OKY-046) on hepatic ischemia-reperfusion injury in rats with obstructive jaundice

The effects of OKY-046, a thromboxane A₂ synthetase inhibitor, on complete hepatic ischemia with obstructive jaundice were studied in male Wistar rats in vivo. The objective of this study was to investigate the influence of OKY-046 (i) on the hepatic microcirculation, as measured by tissue partial oxygen pressure (tPO₂), and (ii) on the release of interleukin-8 (IL-8) in hepatic tissue after reperfusion. Fourteen days after bile duct clamping, the rats were subjected to 30-min warm complete liver ischemia and then reperfusion. The rats were divided into three groups; one group received no treatment (controls, group C), one group received OKY-046 from 15 min before hepatic ischemia to the end of the experiment (group OKY), and the third group received gadolinium chloride (group Gd), injected intravenously to evaluate the contribution of the Kupffer cell to IL-8 production. Group OKY maintained significantly higher tPO₂ levels 5, 10, and 15 min after declamping compared to group C (P<0.05). The IL-8 level in liver tissue in group OKY was lower than that in group C, but the difference was not significant. Group Gd exhibited the lowest IL-8 level of the three groups (P < 0.05). These findings demonstrated that OKY-046 improved the hepatic microcirculation during the reperfusion period, influenced the Kupffer cells in terms of the avoidance of hypoxia, and depressed the concentration of IL-8 in liver tissue.