Effects of magnesium acetate on the toxicity of nickelous acetate in rats.

The effects of subcutaneous (s.c.) injections of magnesium acetate (MgAcet) on the acute toxicity of intraperitoneal (i.p.) nickelous acetate (NiAcet) were studied in rats. Male F344/NCr rats, 150-200 g body wt, received either NiAcet alone, MgAcet alone, or both. The dose of NiAcet was 115 mumol/kg body wt for the lethality and 95 mumol/kg body wt for all other tests. MgAcet was given in 400 mumol/kg body wt daily doses at -24, 0, and +24 h relative to NiAcet for the lethality study, or at -24 and 0 h for all other tests. Treatment with MgAcet increased 14-day survival of the NiAcet-injected rats (57% vs. 27%; P less than 0.02) and diminished 24-h nickel uptake in the lung (50%), liver (44%), and kidneys (30%), but not in blood, spleen, heart, or brain. MgAcet also increased (15% in 0-3 h) urinary excretion of nickel. It had no effect, however, on nickel-induced nephropathy, hyperglycemia, lipid peroxidation in liver and kidneys, and decrease in renal cytochrome P-450 content. Neither NiAcet nor MgAcet had any effect on the ATPase activity in heart and brain. These results suggest that MgAcet decreases the lethality of NiAcet by altering the pharmacokinetics of nickel(II) and not by enhancement of a pharmacodynamic tolerance to nickel(II).