title: Platinum Complexes-Induced Cardiotoxicity of Isolated, Perfused Rat Heart: Comparison of Pt(II) and Pt(IV) Analogues Versus Cisplatin.
abstract: We have compared the cardiotoxicity of five platinum complexes in a model of isolated rat heart using the Langendorff technique. These effects were assessed via coronary flow (CF) and cardiac functional parameters. cis-Diamminedichloroplatinum(II) (cisplatin, CDDP), dichloro-(1,2-diaminocyclohexane)platinum(II) (Pt((II))DACHCl2), dichloro-(ethylenediamine)platinum(II) (Pt((II))ENCl2), tetrachloro-(1,2-diaminocyclohexane)platinum(IV) (Pt((IV))DACHCl4) and tetrachloro-(ethylenediamine)platinum(IV) (Pt((II))ENCl4) were perfused at increasing concentrations of 10(-8), 10(-7), 10(-6), 10(-5) and 10(-4) M during 30 min. In this paper, we report that cisplatin-induced dose-dependent effects on cardiac contractility and coronary flow both manifested as decrease in cardiac contractile force (dP/dt)max, heart rate and significant reduction in CF. Pt((II))ENCl2, Pt((IV))ENCl2 and Pt((IV))DACHCl4 did induce dose-dependent response only in case of CF. Our results could be also important for better understanding dose-dependent side effects of potential metal-based anticancer drugs.
authors.affiliation: College for Specialized Studies in Belgrade, Cara Dusana 254, 11080, Zemun, Serbia.
authors.forename: Miroslav M
authors.initials: MM
authors.lastname: Misic
authors.forename: Vladimir L
authors.initials: VL
authors.lastname: Jakovljevic
authors.forename: Zivadin D
authors.initials: ZD
authors.lastname: Bugarcic
authors.forename: Vladimir I
authors.initials: VI
authors.lastname: Zivkovic
authors.forename: Ivan M
authors.initials: IM
authors.lastname: Srejovic
authors.forename: Nevena S
authors.initials: NS
authors.lastname: Barudzic
authors.forename: Dragan M
authors.initials: DM
authors.lastname: Djuric
authors.forename: Slobodan S
authors.initials: SS
authors.lastname: Novokmet
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D066126:Cardiotoxicity / Q000473:pathology / Q000503:physiopathology*; D002945:Cisplatin / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology*; D008297:Male; D009924:Organ Culture Techniques; D017671:Platinum Compounds / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000970:Antineoplastic Agents; D017671:Platinum Compounds; D002945:Cisplatin