EFFECTS OF OP-2507, A STABLE ANALOG OF PROSTAGLANDIN I-2, ON CARBON TETRACHLORIDE-INDUCED LIVER-DAMAGE IN STARVED RATS

It has been reported that vasodilatory prostaglandins have cytoprotect ive effects against various types of liver damage. We investigated the effects OP 2507, a stable analogue of prostaglandin I-2, on carbon te trachloride-induced liver damage in starved rats. Intraperitoneal admi nistration of OP 2507 at 1,500 mu g/kg lessened both an increase in se rum alanine aminotransferase activity and an inhibition of starvation ketosis, both of which were induced by carbon tetrachloride. At lower doses, however, OP 2507 not only failed ta ameliorate the carbon tetra chloride-induced changes, but it actually exaggerated them. Although t he deterioration of carbon tetrachloride-induced liver damage by lower doses of OP 2507 was not statistically significant, it seems possible that OP 2507 has dual effects on carbon tetrachloride-induced liver d amage. While none of the three agents cimetidine, reduced glutathione and deferoxamine, prevented increase in serum alanine aminotransferase activity induced with lower dose OP 2507, allopurinol had a tendency to prevent the increase, indicating that lower doses of OP 2507 may pr omote a reaction catalyzed by xanthine oxidase. We propose that both t he co-administration of prostaglandins and other potentially hepatotox ic drugs, and the administration of prostaglandins to patients with dr ug-induced liver damage should be done carefully.