TOXICITY AND EXCRETION OF CISPLATIN IN THE AVIAN KIDNEY

Cisplatin is a widely applied antineoplastic drug with significant nep hrotoxic potential. The purpose of this study was to define the toxic effect and excretion of cisplatin in the chicken, a species widely app lied to the study of tubular transport mechanisms but little used for toxicology studies, Toxicity was assessed by the relative effect of ci splatin on renal clearances of the standard reference substrates inuli n and p-aminohippurate (PAH) and by morphologic assessment of the kidn eys of cisplatin-treated chickens. The data clearly support close simi larities in the pattern of tubular cell damage produced in the chicken versus that reported for rats and human patients, It was further demo nstrated that administration of an organic cation reduced Pt accumulat ion in the kidney and mitigated the toxicity as has been reported for rats. Excretion studies were carried out during unilateral renal porta l infusion of cisplatin, and the results indicated that cisplatin does not undergo net tubular secretion as occurs in the rat and human, It can be concluded that, while the pattern of cisplatin-induced nephroto xicity closely parallels that seen in mammals, the avian kidney exhibi ts a different pattern of urinary Pt excretion than does the mammalian kidney after cisplatin administration.