Lithium-induced increase in the metabolism of benzo[a]pyrene and drugs in rat liver.

Administration of lithium chloride (2.5 mEq/kg/day) to rats for 4 or 12 days increased the rates of hepatic hydroxylation of benzo[a] pyrene, antipyrine and zoxazolamine by 100, 114 and 56 per cent, respectively, and the rate of hepatic conjugation of 4-methylumbelliferone with glucuronic acid by 19 per cent. Liver lithium levels were highly correlated with plasma lithium levels but not with hepatic benzo[a] pyrene hydroxylase activities. In vitro addition of lithium to liver 10,000 g supernatants did not affect the hydroxylation of benzolalpyrene, suggesting that the lithium-induced increase in hepatic drug hydroxylation is not due to enzyme activation and is probably a result of lithium-mediated enzyme induction.