Cytochrome P450 content and ultrastructural changes in liver of zinc-treated C57/6J mice

In a previous report, we have demonstrated that acute zinc administration 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 any influence on the zinc effects and (b) the hepatocytes at the ultrastructural level. Two doses of zinc chloride at 28 mu g g(-1) body weight (equivalent to LD(50) in chronic treatment) were administered intraperitoneally to male and female C57/6J mice at 24 h intervals. Significant reduction of hepatic cytochrome P450 content was observed to occur the next day in both acutely treated male and female mice. On examination under transmission electron microscopy, evidence was found of toxic 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 Chang liver cells. The findings indicate that acute zinc administration reduced the hepatic cytochrome P450 content in C57/6J mice irrespective of gender. (C) 1996 The Italian Pharmacological Society.