Lipid Peroxidation as a Mechanism of Cisplatin-Induced Nephrotoxicity
Cisplatin (cis-platinum-II-diammine dichloride, CP), an antitumour agent against many solid tumours (1), causes as a major side-effect nephrotoxicity (2). Nephrotoxicity has an occurrence of 25–75% in humans (3), depending on single or multiple course therapy. The mechanism of the CP-induced nephrotoxicity is not well known. The administration of antioxidants or radical scavengers reduces the CP-induced nephrotoxicity in vivo (4–6). Increased in vivo production of the lipid peroxidation product malondialdehyde in the kidney after CP-treatment of the rat, has been shown very recently (5). In the present in vitro study, the effect of CP, and the combined effect of CP and antioxidants or radical scavengers on lipid peroxidation and pyruvate-stimulated gluconeogenesis in rat renal cortical slices were investigated. It has been shown that rat renal cortical slices accumulated CP manifold above the concentration in the incubation medium, involving an interaction with the organic base carrier system at the basolateral side of proximal tubular cells (7). Transport into the tubular cells across the luminal membrane seems not to be a prerequisite of CP-induced nephrotoxicity, since nonfiltering kidneys developed toxicity after CP-treatment (8), and recovery of radiolabelled CP in the urine after microinjection into early segments of proximal tubules was 94% (9).
KeywordsIncubation Medium Proximal Tubular Cell Luminal Membrane Basolateral Side Control Slice
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