Induction of hepatic metallothionein by alcohols: Evidence for an indirect mechanism

Abstract

The purpose of the present study was to determine the ability of various short-chain alcohols to induce metallothionein (MT) in the liver and to determine whether the induction results from a direct action of alcohol on liver or an indirect action mediated by zinc, glucocorticoids, or catecholamines. Mice were administered alcohol by gavage and hepatic MT was quantitated by the Cd-hemoglobin radioassay. Ethanol, methanol, isopropanol, and propanol increased MT content to seven to nine times that of control liver. In vitro, ethanol did not increase MT concentrations in rat hepatocyte cultures, indicating that the in vivo induction is not a direct effect of ethanol on the liver. Adrenergic blocking agents did not reduce the MT content of ethanol-treated mice, indicating that catecholamines are probably not involved in the MT induction. Corticosterone and zinc concentrations in plasma were increased in mice 1 hr after ethanol treatment. Corticosterone, give in vivo, was a less effective inducer of MT than was ethanol treatment. In conclusion, (1) hepatic MT was increased by several alcohols, (2) the induction was not due to direct action of alcohol on the liver, and (3) while the mechanism of alcohol induction of MT is unclear, it may be due to an alteration in zinc and glucocorticoid homeostasis.