PROTECTIVE EFFECT OF THE THROMBOXANE-A(2) RECEPTOR ANTAGONIST ONO-3708 ON ISCHEMIA-REPERFUSION INJURY IN THE DOG LIVER

Background. Prostaglandins are widely known to have cytoprotective eff ects in a variety of conditions. Thromboxane A(2) has the opposite eff ect of prostaglandins. In this study the effects of the thromboxane A( 2) receptor antagonist ONO 3708 on ischemia and subsequent reperfusion in the dog liver was evaluated.Methods. Mongrel dogs weighing from 10 to 15 kg were divided into three groups: a control group, a group wit h induced liver ischemia and subsequent reperfusion, and a group that received ONO 3708 and then underwent induced liver ischemia and subseq uent reperfusion. Liver ischemia was induced by the Pringle procedure for 60 minutes. The concentrations of total free amino acids, aromatic amino acids, and branched-chain amino acids in blood taken from the p ortal and hepatic veins were examined before and after the Pringle pro cedure in the latter two groups and at the corresponding points in the control group. Results. Disturbances in amino acid metabolism in the liver occurred 5 minutes after the declamping in the ischemic group, a nd prostaglandin I-2 and thromboxane A(2) levels and lipid peroxide pr oduction, were increased. In contrast, hepatic amino acid metabolism w as unchanged, and prostaglandin I-2 and thromboxane A(2), and lipid pe roxide production, were normalized in the group that was treated with ONO 3708. Conclusions. ONO 3708 appears to protects hepatic tissue fro m ischemia-reperfusion injury through free-radical scavenging, by incr easing prostaglandin I-2 levels, and by decreasing thromboxane A(2) pr oduction.