Lipid peroxidation as a mechanism of acute nickel toxicity†

Abstract

Studies in the author's laboratory have shown that (a) concentrations of thiobarbituric acid (TBA) chromogens are increased in target tissues (liver, kidney, lung) of NiCl₂‐treated rats; (b) severity of hepatic toxicity, assessed by serum aspartate aminotransferase activity, is generally proportional to the elevation of hepatic TBA‐chromogens, based upon the time‐courses and dose‐effect relationships observed after administration of NiCl₂ to rats; (c) concentrations of conjugated dienes are greatly elevated in lipid extracts of hepatic microsomes from NiCl₂‐treated rats; (d) NiCl₂‐toxicity in rats is attended by increased exhalation of ethane and ethylene, decreased erythrocyte deformability, and elevated concentrations of plasma lipoperoxides. Studies in other laboratories have shown that (e) TBA‐chromogens are increased in brain homogenates of rats after repeated daily injections of NiCl₂; (f) hepatic microsomes from NiCl₂‐treated rats yield increased rates of lipid peroxidation when incubated in vitro with NADPH or ascorbate; and (g) addition of NiCl₂ to rat liver homogenates stimulates lipid peroxidation during in vitro incubation with NADPH or ascorbate. These experimental findings support the conclusion that lipid peroxidation constitutes a molecular mechanism of acute nickel toxicity.