Background: Prostaglandin I2 (PGI2) analogues have been suggested to protect the liver from ischemia-reperfusion injury, but the exact mechanism remains to be proved.
Methods: 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.
Results: 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.
Conclusions: 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.