Failure of exogenous prostaglandin to afford complete protection against acetaminophen‐induced hepatotoxicity in the rat

The protective effect of 16,16‐dimethylprostaglandin E2 (dm‐PGE2) against acetaminophen‐induced hepatotoxicity was determined in the rat. The dm‐PGE2 was administered at two dose levels both before and after acetaminophen administration. The hepatotoxicity was evaluated by a rise in serum transaminases 24 h after acetaminophen administration and by histological examination of liver preparations. The urinary acetaminophen and its metabolites were determined by high‐pressure liquid chromatography. The results suggest that exogenous dm‐PGE2 administration had a modest protection against acetaminophen‐induced hepatotoxicity, in contrast to its well established cytoprotective effect against many noxious agents in the gastrointestinal tract. Prosta‐glandin treatment had little effect on acetaminophen metabolites excretion in the urine, suggesting that it did not affect the cytochrome P‐450‐dependent mixed‐function oxidase drug‐metabolizing enzyme system. The livers from dm‐PGE2‐acetaminophen‐treated rats showed...