16,16-DIMETHYL PROSTAGLANDIN-E2 MODULATES AFLATOXIN B1-INDUCED INJURY OF RAT HEPATOCYTES IN PRIMARY CULTURE - POSSIBLE ROLE OF CAMP

The hepatocellular cytoprotective effects of 16,16-dimethyl prostaglandin E2 (dmPGE2), ananalogue of PGE2, were investigated using primary cultures of rat hepatocytes and aflatoxin B1 as the hepatotoxin. Lactic dehydrogenase (LDH) release by hepatocytes was used as an index of hepatotoxicity. When aflatoxin-treated hepatocytes were co-cultured with 16,16-dmPGE2 (0.01-0.5 mug/mL) LDH release was significantly reduced and ultrastructural changes of hepatocellular injury were markedly diminished. The magnitude of the cytoprotective effect was not dependent on the concentration of the prostaglandin over the range tested. A significant cytoprotective effect was also induced when hepatocellular cyclic AMP (cAMP) levels were increased by the addition of dibutyl-cAMP. In contrast to 16,16-dmPGE2, PGF2alpha Tromethamine, an analogue of PGF2alpha, which does not stimulate cAMP, induced insignificant changes in cytoprotection. These findings indicate that only a low concentration of 16,16-dmPGE2 (greater-than-or-equal-to 0.01 mug/mL) is necessary to induce a maximal hepatocellular cytoprotective effect and suggest that this effect may be dependent on activation of cAMP.