Cisplatin Nephrotoxicity in Cadmium-Pretreated Rats

Abstract

Treatment of rats with cisplatin or with cisplatin after chronic pre-exposure to cadmium induced a decrease in kidney cytochrome P-450 and glutathione levels, and in glutathione peroxidase and reductase activities. Furthermore, cadmium and cisplatin enhanced lipid peroxidation, oxidized glutathione and N-glucuronyl transferase activity. Glutathione S-transferase (substrate: 1-chloro-2,4-dinitrobenzene) was increased and decreased by cadmium and cisplatin respectively. On morphological observation, cadmium nephrotoxicity was characterized by tubular proximal damage with mitochondrial and lysosomal changes and a widespread vesiculation of tubular cells. A marked focal tubular necrosis associated with cyst formation was observed in cisplatin nephrotoxicity. On the basis of the measured biochemical, functional and histological parameters, it is concluded that cadmium pretreatment did not potentiate the nephrotoxic effect of cisplatin.

Ci̇splati̇ni̇n Siçan Böbrek Ve Testi̇sleri̇ Üzeri̇ne Etki̇leri̇

“…Cisplatin enjeksiyonundan 72 saat sonra çekirdekte DNA sentezinin hız-lanması ise renal tübüler hücrelerinde rejenerasyonun göstergesidir (6). Dahası elektron mikroskobu çalışma-larında tübüler bazal membran duplikasyonıınun varlığı da rejeneratif sürecin başladığı yönünde bir işaret olarak değerlendirilmiştir (7). Bu çalışmada ilaç uygulaması düşük dozda uzun süreli verildiğinden epitelde dökülme tesbit edilmiş ancak rejenerasyon izlenmemiştir.…”