Carboplatin-induced alteration of the thiol homeostasis in the isolated perfused rat kidney.
Carboplatin elicits minor side effects with respect to its first generation analogue cisplatin. Nevertheless, a dose-dependent nephrotoxicity of the drug has been reported to occur both in patients and in rats and a possible pathogenic role have been attributed to oxidative stress. We have studied the effect of carboplatin administration on the thiol/disulfide balance, on other biomarkers of oxidative stress and on antioxidant enzymes in the isolated perfused rat kidney. A 5-500microM carboplatin dose range did not alter renal function but significantly decreased levels of cysteine, glutathione and exposed protein sulfhydryl groups. Only a minimal increment in disulfides was observed, whereas malonyldialdehyde and protein carbonyls did not increase significantly. Among the antioxidant enzymes studied, only thioltransferase was inhibited by the treatment. Our data suggest that a minimal oxidative stress is present under our experimental conditions, thus indicating that platinum-based drugs do not produce significant amount of reactive oxygen species.
Giustarini
Daniela
D
Department of Evolutionary Biology, Laboratory of Pharmacology and Toxicology, University of Siena, Siena, Italy. giustarini@unisi.it
Dalle-Donne
Isabella
I
Paccagnini
Eugenio
E
Milzani
Aldo
A
Rossi
Ranieri
R
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D000975:Antioxidants / Q000378:metabolism; D016190:Carboplatin / Q000008:administration & dosage / Q000494:pharmacology*; D004220:Disulfides / Q000378:metabolism / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D006706:Homeostasis / Q000187:drug effects*; D066298:In Vitro Techniques; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013438:Sulfhydryl Compounds / Q000378:metabolism* / Q000652:urine
D000970:Antineoplastic Agents; D000975:Antioxidants; D004220:Disulfides; D004791:Enzyme Inhibitors; D013438:Sulfhydryl Compounds; D016190:Carboplatin