Reduction of Cisplatin-Induced Nephrotoxicity in Vivo by Selenomethionine: The Effect on Cisplatin鈥揇NA Adducts

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• 作者：Daniel Garci虂a Sar ; Maria Montes-Bayo虂n ; Elisa Blanco Gonza虂lez ; Luisa M. Sierra Zapico ; Alfredo Sanz-Medel
• 刊名：Chemical Research in Toxicology
• 出版年：2011
• 出版时间：June 20, 2011
• 年：2011
• 卷：24
• 期：6
• 页码：896-904
• 全文大小：950K
• 年卷期：v.24,no.6(June 20, 2011)
• ISSN：1520-5010

文摘

Cisplatin is one of the most effective chemotherapeutic agents, although its clinical use is limited by severe renal toxicity. This toxicity seems to be related to the accumulation of the drug in kidney tissues, leading to renal failure. For this reason, several compounds have been evaluated to ameliorate the nephrotoxicity induced by cisplatin. In the present investigation, we report the effect of the oral administration of selenomethionine before intraperitoneal cisplatin treatment. The preadministration of this Se species has been shown to have an important effect in reducing renal damage induced by cisplatin by increasing the excreted urea and improving creatinine clearance. Quantification of the level of DNA鈥揷isplatin adducts in kidney and liver tissues was carried out by postcolumn isotope dilution analysis using liquid chromatography-inductively coupled plasma (LC-ICP-MS) as speciation set up. The level of DNA鈥揷isplatin adducts in rats given Se-methionine in the drinking water before cisplatin administration was considerably lower in kidney tissues with respect to the animals drinking only water. Such effects were not observed in liver tissue. Initial speciation studies of Pt and Se conducted in kidney tissues of exposed animals by HPLC-ICP-MS have revealed the presence of cisplatin as part of a complex with Se-methionine, which can be eventually excreted into urine. This Pt鈥揝e complex could explain the observed reduction of the kidney damage in Se-methionine-treated animals.