Toxicity and excretion of cisplatin in the avian kidney.
Cisplatin is a widely applied antineoplastic drug with significant nephrotoxic potential. The purpose of this study was to define the toxic effect and excretion of cisplatin in the chicken, a species widely applied to the study of tubular transport mechanisms but little used for toxicology studies. Toxicity was assessed by the relative effect of cisplatin on renal clearances of the standard reference substrates inulin and p-aminohippurate (PAH) and by morphologic assessment of the kidneys of cisplatin-treated chickens. The data clearly support close similarities in the pattern of tubular cell damage produced in the chicken versus that reported for rats and human patients. It was further demonstrated that administration of an organic cation reduced Pt accumulation in the kidney and mitigated the toxicity as has been reported for rats. Excretion studies were carried out during unilateral renal portal 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 nephrotoxicity closely parallels that seen in mammals, the avian kidney exhibits a different pattern of urinary Pt excretion than does the mammalian kidney after cisplatin administration.
Division of Pharmacology and Medicinal Chemistry, College of Pharmacy, University of Cincinnati Medical Center, OH 45267-0004, USA.
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D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity* / Q000652:urine; D002645:Chickens; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity* / Q000652:urine; D005260:Female; D007444:Inulin / Q000652:urine; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism; D010984:Platinum / Q000097:blood / Q000652:urine; D011803:Quinine / Q000494:pharmacology; D012079:Renal Circulation / Q000187:drug effects; D010130:p-Aminohippuric Acid / Q000652:urine
D000970:Antineoplastic Agents; D010984:Platinum; D007444:Inulin; D011803:Quinine; D002945:Cisplatin; D010130:p-Aminohippuric Acid