Inhibition of S-(1,2-dichlorovinyl)-L-cysteine-induced lipid peroxidation by antioxidants in rabbit renal cortical slices: Dissociation of lipid peroxidation and toxicity

✍ Scribed by Davis, Joe W. ;Petry, Thomas W.

• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: English
• Weight: 886 KB
• Volume: 9
• Category: Article
• ISSN: 0887-2082
• DOI: 10.1002/jbt.2570090303

✦ Synopsis

Precision-cut, rabbit renal slices were used to examine the effects of three novel antioxidants (U-74006, U-74500, and U-78517) on 5-(1,2-dichloroviny1)-L-cysteine (DCVC)-induced lipid peroxidation and toxicity. Slices exposed to DCVC showed a dose-and time-dependent increase in lipid peroxidation (TBARS) and a decrease in cellular viability, as evidenced by the loss of intracellular potassium, during the course of a 3 hour incubation. Subsequent studies employed DCVC concentrations of 100 pM. Microemulsion formulations of U-78517, U-74500, and U-74006 (100 pM) inhibited DCVC-induced lipid peroxidation by 1002, 502, and <5R (not significant), respectively. However, none of these antioxidants had a significant effect on DCVC-dependent cytotoxicity, as indicated by intracellular potassium release. The effects of U-78517, the most potent of the three antioxidants, were similar to those observed with two model antioxidants, diphenyl-p-phenylenediamine (DPPD) and the iron chelator, deferoxamine. Aminooxyacetic (AOAA), an inhibitor of renal cysteine conjugate P-lyase, had only a minimal effect on DCVC-induced lipid peroxidation, and no effect on toxicity.

These data represent the first report of DCVCinduced lipid peroxidation in rabbit renal cortical slices, a system which has been widely used to investigate mechanisms of nephrotoxicity, including that induced by DCVC. Our results demonstrate that DCVC-induced lipid peroxidation in renal slices can be inhibited by a variety of antioxidant compounds operating by different mechanisms. Because inhibition of lipid peroxidation had minimal effect on DCVC-dependent cytotoxicity, the data suggest that DCVC-induced lipid peroxidation is not a major mechanism in the cytotoxicity induced by this compound.