CYTOCHROME-P450 CONTENT AND ULTRASTRUCTURAL-CHANGES IN LIVER OF ZINC-TREATED C57 6J MICE/

In a previous report, we have demonstrated that acute zinc administrat ion reduced the hepatic cytochrome P450 content in female C57/6J mice. In this extended toxicological study, we investigated the effects of zinc administration on (a) the hepatic cytochrome P450 content of both male and female mice to evaluate whether the sex of the animal had an y influence on the zinc effects and (b) the hepatocytes at the ultrast ructural level. Two doses of zinc chloride at 28 mu g g(-1) body weigh t (equivalent to LD(50) in chronic treatment) were administered intrap eritoneally to male and female C57/6J mice at 24 h intervals. Signific ant reduction of hepatic cytochrome P450 content was observed to occur the next day in both acutely treated male and female mice. On examina tion under transmission electron microscopy, evidence was found of tox ic injury to the hepatocytes of mice livers in the zinc-treated group. Glutathione-monochlorobimane adduct formation (which is specifically catalysed by glutathione transferase) was found to be depressed in Cha ng liver cells. The findings indicate that acute zinc administration r educed the hepatic cytochrome P450 content in C57/6J mice irrespective of gender. (C) 1996 The Italian Pharmacological Society.