title: Reduction of cisplatin-induced nephrotoxicity in vivo by selenomethionine: the effect on cisplatin-DNA adducts.
abstract: 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--cisplatin 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--cisplatin 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--Se complex could explain the observed reduction of the kidney damage in Se-methionine-treated animals.
authors.affiliation: Department of Physical and Analytical Chemistry, Faculty of Chemistry, University of Oviedo, C/Julian Clavería 8, 33006 Oviedo, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: García Sar
authors.forename: Maria
authors.initials: M
authors.lastname: Montes-Bayón
authors.forename: Elisa
authors.initials: E
authors.lastname: Blanco González
authors.forename: Luisa M
authors.initials: LM
authors.lastname: Sierra Zapico
authors.forename: Alfredo
authors.initials: A
authors.lastname: Sanz-Medel
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001835:Body Weight; D002945:Cisplatin / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity*; D003404:Creatinine / Q000097:blood / Q000652:urine; D018736:DNA Adducts / Q000032:analysis / Q000378:metabolism*; D004347:Drug Interactions; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced* / Q000188:drug therapy; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008958:Models, Molecular; D010984:Platinum / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012643:Selenium / Q000032:analysis / Q000378:metabolism; D012645:Selenomethionine / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D018736:DNA Adducts; C057270:cisplatin-DNA adduct; D010984:Platinum; D012645:Selenomethionine; D003404:Creatinine; D012643:Selenium; D002945:Cisplatin