Changes in rat liver metallothionein and metallothionein mRNA induced by isopropanol.

Administration of isopropanol (1 ml/kg body weight) via the ip route significantly depressed the serum zinc concentration within 8 hr. A maximal increase in hepatic metallothionein was observed 16 hr after isopropanol. By 48 hr after treatment metallothionein levels in liver had returned to basal levels. The extent of metallothionein induction was comparable with that observed after ip administration of zinc. Plasma glucagon concentrations were significantly elevated 4 hr after isopropanol treatment. Adrenalectomy did not prevent the isopropanol-induced changes in serum zinc or hepatic metallothionein. This suggests a nonadrenal mechanism is responsible for the observed changes. To evaluate changes in metallothionein mRNA levels in liver, in vitro translation with the wheat germ system was used to evaluate translational activity. Analysis of the labeled metallothionein produced in vitro employed both covalent chromatography as well as SDS-polyacrylamide gel electrophoresis of carboxymethylated translation products. These methods suggested the maximum metallothionein mRNA level in total RNA extract occurred about 8 hr after administration of isopropanol. Similarly, when metallothionein mRNA levels were quantitated using dot blot hybridization to [32P]cDNA for mouse metallothionein I, maximum metallothionein mRNA appeared 8 hr after isopropanol administration. The overall response of these parameters in rats suggest that isopropanol administration leads to an inflammatory-like response that, with respect to zinc metabolism, has elements which are independent of the adrenal gland, but involve transcriptional regulation of the metallothionein gene in liver.