Transient induction of hepatic metallothionein following oral ethanol administration

Abstract

Chronic ethanol ingestion has been associated with alterations of zinc homeostasis. Various treatments that alter zinc disposition induce hepatic metallothionein (MT). Therefore, this study was performed to determine the effect of acute ethanol exposure on hepatic MT levels. Adult male CF-1 mice were administered ethanol intragastrically and their hepatic MT was quantified at various times thereafter by the Cd-radioassay method. Ethanol (5 g/kg, ig) produced significant increases in hepatic MT as early as 4 hr after dosing. Maximal hepatic MT concentrations (19-fold increase) were observed 24 hr after ethanol and returned to control concentrations by 48 hr. Hepatic MT levels were increased 24 hr after 5 or 7 g ethanol/kg but were not altered by 1, 2, or 3 g/kg. Elevations in pancreatic MT, but not in renal or intestinal MT, also occurred 24 hr after ethanol (5 g/kg). Actinomycin D (1.25 mg/kg, ip) prevented the increase in hepatic MT produced by ethanol, whereas inhibition of ethanol oxidation by pyrazole (150 mg/kg, ip) did not prevent the induction of hepatic MT. Gel filtration chromatography and uv spectral analysis confirmed the presence of MT in the livers of ethanol-treated mice. These data show that acute ethanol administration produces a marked elevation of hepatic MT that is transient.