The Platinum(II) Complexes Induced Oxidative Stress of Isolated Rat Heart

Serbian Journal of Experimental and Clinical Research

Radonjic Katarina¹  Stojic Isidora¹  Novokmet Slobodan¹  Jeremic Nevena¹  Srejovic Ivan²  Zivkovic Vladimir²  Jakovljevic Vladimir²  Djuric Dragan³ 

[1] Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Serbia;Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Serbia;Institute of Medical Physiology “Richard Burian”, Faculty of Medicine, University of Belgrade, Serbia;

关键词: cisplatin;    1,2-diaminocyclohexane;    isolated rat heart;    oxidative stress;    perfusion;    platinum(ii) complexes;   

DOI  :  10.1515/sjecr-2016-0059

来源: DOAJ

【 摘 要 】

Interest for the clinical application of transition metal complexes as chemotherapeutic agents initially started with discovery of cisplatin. Despite the remarkable clinical success, cisplatin treatment is limited due to its resistance and side effects. Over the last 40 years, numerous transition metal complexes were synthesized and investigated in vitro and in vivo in order to establish a metallopharmaceutical that will exert less toxicity and equal or higher potency. We have compared the cardiotoxicity of 2 platinum complexes, one ligand, and a starting salt for complex synthesis using an experimental model of an isolated, perfused rat heart according to the Langendorfftechnique. The cardiotoxicity was assessed by comparison of oxidative stress induced following the perfusion of the following compounds: Dichloro(1,2-diaminocyclohexane)platinum(II), cisplatin, potassium-tetra-chloroplatinum(II) and 1,2-diaminocyclohexane, which were perfused at increasing concentrations from 10−8 to 10−4 M for 30 minutes. The oxidative stress was assessed by determination of superoxide anion radical, hydrogen peroxide, thiobarbituric acid reactive substances, and nitric oxide from the coronary venous effluent. Our results showed that the levels of oxidative stress parameters were not significantly affected by perfusion with all the tested compounds and were not dose-dependent. These results could be of importance to further investigations concerning the effects of platinum-based potential anticancer drugs on the heart.

【 授权许可】

Unknown