Effect of various diuretics on lipid peroxidation in rat renal cortical mitochondria and in the supernatant.

Abstract

Effect of various diuretics of lipid peroxidation in rat kidney cortical mitochondria and in the supernatant (11,000 x g) was studied. Mersalyl (mercurial diuretic) markedly stimulated the lipid peroxidation in mitochondria and in the supernatant at a concentration of 1 mM, and metolazone (sulfonamide derivative, 1 mM) stimulated only that in the supernatant. Mersalyl-induced lipid peroxidation was markedly inhibited by several classical radical scavengers such as sodium diethyldithiocarbamate, 2,6-di-tert-butylphenol and N,N'-diphenyl-p-phenylenediamine, but metolazone-induced lipid peroxidation was not inhibited by these scavengers. The addition of superoxide dismutase to the reaction mixture inhibited the mersalyl-induced lipid peroxidation, but did not inhibit the peroxidation by metolazone or ascorbate. These results suggest that lipid peroxidation by mersalyl is mediated by free radicals or superoxide anion, which were probably produced by mersalyl, and the mercurial diuretics-induced nephrotoxicity may be due to the lipid peroxidation in the kidney.