K. Irita et al., EFFECTS OF OP-2507, A STABLE ANALOG OF PROSTAGLANDIN I-2, ON CARBON TETRACHLORIDE-INDUCED LIVER-DAMAGE IN STARVED RATS, Tohoku Journal of Experimental Medicine, 178(3), 1996, pp. 279-285
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.