Distribution of Platinum Amongst the Subcellular Organelles of the Rat Kidney After Oral Administration of Cisplatin

Abstract

Cisplatin is an effective anticancer agent when administered i. v. to experimental animals and man (1). Its use, however is limited by its toxicity to a number of organs including the kidney (2). These side effects can be modulated by the use of second generation analogues such as carboplatin (3) and alternative routes of administration. Recent studies have demonstrated that cisplatin is orally absorbed, that the nephrotoxicity associated with the compound could be significantly reduced using this route and that oral cisplatin is effective against several murine tumours (4). We have previously reported that oral cisplatin (in rats) could potentiate its hepatotoxicity, although the greatest proportion of the absorbed Pt is still associated with the kidney (5). In this study we have examined the uptake and subcellular localization of platinum in the rat kidney cortex following oral administration of cisplatin with the aim of identifying the sites of Pt accumulation and relating this to the nephrotoxicity.