AGE-RELATED EFFECTS OF LITHIUM-CHLORIDE ON METALS, METALLOTHIONEIN, CYTOCHROME-P450 AND HEME OXYGENASE IN THE LIVER OF RATS

The effects of lithium chloride (LiCl) on the concentrations of metals (lithium and zinc), metallothionein (MT) and cytochrome P-450 and on the activity of heme oxygenase were investigated in the liver of 3-(immature) and 48-week-old (adult) rats at 6 h after the single or the repeated LiCl treatment. Animals were given a single (200 mg/kg) or repeated (53 mg/kg every 12 h for 7 d) i.p. injection. Serum lithium (Li) concentration was higher in adult rats than in the immature rats after a single LiCl (200 mg/kg, i.p.) administration. No significant alteration due to age was observed in hepatic cytosol Li concentrations after the single LiCl treatment. Whereas the marked enhancement of heme oxygenase and MT level was present with both groups after the single treatment of LiCl, the decreasing of cytochrome P-450 concentration was observed only in the immature rats. In the case of the repeated LiCl treatment, Li levels both in serum and in the hepatic cytosol were notably higher in the adult rats than in the immature rats, but the more significant alterations on parameters such as heme oxygenase, cytochrome P-450 and MT were observed in the immature rats rather than in the adult rats. Aminopyrine N-demethylase activity which is one of the drug metabolizing enzymes activities related to cytochrome P-450 was decreased in the liver of the immature rats exposed to repeated LiCl treatment. On the other hand, aniline hydroxylase activity in the liver of the adult rats was increased by repeated Li treatment. In this study, the more severe effects due to Li treatment were found in the immature rats.