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Toxic Effects of Metallopharmaceuticals

References 1. Jakupec MA, Galanski M, & Keppler BK. (2003). Tumour- inhibiting platinum complexes--state of the art and future perspectives. Reviews of Physiology, Biochemistry and Pharmacology, 146, 1-54. 2. Sakurai H. (2010). Overview and frontier for the development of metallopharmaceutics. Journal of Health Science, 56(2), 129-143. 3. Clarke MJ, Zhu F, & Frasca DR. (1999). Non-platinum chemotherapeutic metallopharmaceuticals. Chemical Reviews, 99(9), 2511-2534. 4. Donzelli E, Carfi M, Miloso

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

Abstract

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.

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