The role of lipid peroxidation in the nephrotoxicity of cisplatin.
The possible role of lipid peroxidation in the nephrotoxicity of the antitumour drug cisplatin was studied in vitro. In contrast to Adriamycin, cisplatin did not induce lipid peroxidation in rat kidney microsomes containing a NADPH-generating system. Pretreatment of rat kidney microsomes with cisplatin did not reduce the activity of a microsomal glutathione (GSH)-dependent protective factor against lipid peroxidation induced by Fe(2+)-ascorbate. However, pretreatment of rat kidney microsomes with 0.1 mM N-ethyl maleimide (NEM) did reduce this GSH-dependent protection. Cisplatin also did not reduce the activity of a cytosolic GSH-dependent protective factor against Fe(2+)-ascorbate-induced lipid peroxidation. The results of our experiments indicate that, in contrast to Adriamycin, cisplatin does not induce lipid peroxidation in vitro in various test systems. It also does not destroy microsomal and cytosolic GSH-dependent protective factors against lipid peroxidation.
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Department of Pharmacochemistry, Vrije Universiteit, Amsterdam, The Netherlands.
Baldew
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D000818:Animals; D001205:Ascorbic Acid; D002945:Cisplatin / Q000633:toxicity*; D003600:Cytosol / Q000187:drug effects; D004317:Doxorubicin / Q000633:toxicity; D005290:Ferric Compounds; D006358:Hot Temperature; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008861:Microsomes / Q000187:drug effects; D009249:NADP / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D013858:Thiobarbiturates
D005290:Ferric Compounds; D013858:Thiobarbiturates; C024823:ferric sulfate; D009249:NADP; D004317:Doxorubicin; C029684:thiobarbituric acid; D001205:Ascorbic Acid; D002945:Cisplatin