Induction of zinc-thionein by estradiol and protective effects on inorganic mercury-induced renal toxicity

Abstract

The castrated or unoperated male rats received an intravenous injection of HgCl 2; at a dose of 0.7 mg/kg of body weight (b.w.) after pretreatment with 30% ethanol or estradiol dissolved in 30% ethanol at a dose of 0.5 mg/kg b.w. subcutaneously twice a day for six consecutive days. Renal total protein, γ-GTP and K excretion in the rats treated with Hg and estradiol were significantly lower than the corresponding values in the rats treated with Hg alone, suggesting that pretreatment with estradiol ameliorates the renal toxicity of Hg in male rats. Pretreatment with estradiol significantly increased Hg and Hg-thionein(Hg-MT) concentrations in the renal cortex of the animals treated with Hg, though in the liver this agent did increase the Hg-MT without elevation of Hg concentration. Treatment with estradiol alone (0.5 mg/kg, s.c., twice a day, for six consecutive days) significantly increased the zincthionein (Zn-MT) concentration in the kidney and liver. Simultaneous treatment with 10 −5 M estradiol and Hg in human amniotic-fluid cells caused a significant increase in the uptake of Hg and the synthesis of Hg-MT, suggesting that estradiol may directly stimulate an accumulation of Hg into the cells and the synthesis of Hg-MT. Together, all of the above findings suggest that pretreatment with estradiol may increase the uptake of Hg, which in turn leads to the increase in the Hg-MT concentration. The induction of Zn-MT by pretreatment with estradiol may account for the protective effect of estradiol on Hginduced renal toxicity.