Platinum Complexes-Induced Cardiotoxicity of Isolated, Perfused Rat Heart: Comparison of Pt(II) and Pt(IV) Analogues Versus Cisplatin

Cardiovasc Toxicol. 2015 Jul;15(3):261-8. doi: 10.1007/s12012-014-9293-8.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / toxicity*
  • Cardiotoxicity / pathology
  • Cardiotoxicity / physiopathology*
  • Cisplatin / toxicity*
  • Dose-Response Relationship, Drug
  • Heart / drug effects*
  • Heart / physiopathology*
  • Male
  • Organ Culture Techniques
  • Platinum Compounds / chemistry
  • Platinum Compounds / toxicity*
  • Rats
  • Rats, Wistar

Substances

  • Antineoplastic Agents
  • Platinum Compounds
  • Cisplatin