Cytoprotective effect of prostaglandin I2 analogues on superoxide-induced hepatocyte injury.

Abstract

Prostaglandin I2 (PGI2) analogues have been suggested to protect the liver from ischemia-reperfusion injury, but the exact mechanism remains to be proved. Primary cultured rat hepatocytes were exposed to superoxide generated by mixing hypoxanthine and xanthine oxidase, and changes in cell viability, cytosolic free calcium concentration ([Ca2+]i), and adenosine 3',5'-cyclic monophosphate (cAMP) concentration were assessed. The PGI2 analogue (OP2507 or OP41483) at 1 to 100 ng/ml was given as treatment. PGI2 analogues suppressed hepatocyte death in a dose-dependent manner (p < 0.01; OP2507 at 10 and 100 ng/ml, OP41483 at 100 ng/ml). At the end of 1-hour preincubation with OP2507, a significant rise in cAMP concentration was observed. Moreover, addition of dibutyryl cAMP suppressed hepatocyte death. A rise in [Ca2+]i, which preceded cell death, was prevented by PGI2 analogues or dibutyryl cAMP. The increase in cellular cAMP followed by suppression of [Ca2+]i elevation might be the major cause of the cytoprotective effect of PGI2 analogues in superoxide-induced hepatocyte injury.