Effects of diphenyl-phenylenediamine on gentamicin-induced lipid peroxidation and toxicity in rat renal cortex

LS Ramsammy, C Josepovitz, KY Ling, BP Lane and GJ Kaloyanides

The hypothesis that lipid peroxidation is linked causally to the pathogenesis of aminoglycoside nephrotoxicity was tested by determining whether administration of the antioxidant, diphenyl-phenylenediamine (DPPD) would inhibit lipid peroxidation and ameliorate gentamicin- induced proximal tubular cell injury. Rats were injected with saline, gentamicin or gentamicin plus DPPD for 4 days and were sacrificed 48 hr later. Gentamicin increased malondialdehyde in renal cortex from a control level of 0.65 +/- 0.04 to 1.01 +/- 0.03 nmol/mg of protein, P less than .01; it was reduced to 0.20 +/- 0.03 by DPPD, P less than .01 compared to control. Arachidonic acid comprised 27.6 +/- 0.5% of the fatty acid in renal cortical phospholipid of control rats. Gentamicin lowered arachidonic acid to 16.7 +/- 0.9%, P less than .01, and promoted a shift toward saturated fatty acids. DPPD reversed these changes. Gentamicin depressed catalase activity from a control value of 0.211 k/min to 0.154 +/- 0.008 k/min, P less than .01. DPPD depressed catalase further to 0.095 +/- 0.066 k/min, P less than .01. Total glutathione and reduced glutathione were depressed whereas the fraction of total glutathione in the oxidized state was augmented by gentamicin. These changes were prevented by DPPD. The renal cortical phospholipidosis induced by gentamicin was not altered by DPPD. The increased urinary excretions of alanine aminopeptidase and N-acetyl- beta-glucosaminidase induced by gentamicin were augmented further by DPPD. In DPPD rats serum creatinine (0.45 +/- 0.04 mg/dl) was higher (P less than .01) than that of gentamicin rats (0.35 +/- 0.01 mg/dl), which was higher (P less than .01) than that of control rats (0.26 +/- 0.01 gm/dl).(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 238, Issue 1, pp. 83-88, 07/01/1986
Copyright © 1986 by American Society for Pharmacology and Experimental Therapeutics

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