Protective effects of zinc acetate toward the toxicity of nickelous acetate in rats.

Zinc pretreatment is known to ameliorate the acute and chronic effects of the toxic heavy metal, cadmium. However, the ability of zinc to decrease the toxicity of other metals has not been widely investigated. Therefore, this study was designed to determine the effects of zinc pretreatment on the acute toxicity of nickel. Male Fischer rats received either nickel alone (i.p.), zinc alone (s.c.), zinc plus nickel, or saline (i.p. and s.c.; controls). In the lethality studies, the dose of nickel was 115 mumol nickel/kg (as nickel acetate) while for all other studies the dose was 95 mumol nickel/kg. Zinc was given in multiple doses of 300 mumol zinc/kg (as zinc acetate) at -24, 0 and +24 h relative to nickel (total zinc dose 900 mumol/kg) for lethality studies or -24 and 0 h for studies 24 h and under in duration (total dose 600 mumol/kg). Zinc pretreatment significantly increased the 14-day survival of nickel-related rats. Zinc did not, however, prevent the reduction in weight gain over 2 weeks seen with nickel treatment. Histopathologically, at 120 h following nickel exposure, kidneys in the group receiving nickel alone generally showed moderate nephropathy (multifocal proximal tubule degeneration with necrosis) while in the zinc plus nickel group the nephropathy was generally mild. Zinc pretreatment had no apparent effect on the pharmacokinetics of nickel over 24 h as assessed by urinary excretion, blood levels or organ distribution. Zinc pretreatment also did not alter the subcellular distribution of renal nickel 6 h after nickel exposure. Enhanced synthesis of metallothionein did not appear to play a critical role in the reduction of nickel toxicity, since renal concentrations of this metal-binding protein, although elevated compared to control, were not different in rats receiving zinc and nickel or zinc alone. Zinc pretreatment did, however, have marked effect on nickel-induced hyperglycemia, reducing both the duration and severity of elevated blood glucose levels. Results of this study show that zinc can prevent some of the toxic effects of nickel and that the mechanism of this action does not appear to involve either metallothionein or alterations in the pharmacokinetics of nickel.