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

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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.

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Acknowledgments

Authors are very grateful to Prof. Dr. S. Jankovic for permission to use “PIPA” program for calculations. This work was supported by Grant Nos. 175043 and 175007 of the Ministry of Education, Science and Technological Development of Republic of Serbia.

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Authors and Affiliations

  1. College for Specialized Studies in Belgrade, Cara Dusana 254, 11080, Zemun, Serbia

    Miroslav M. Misic

  2. Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000, Kragujevac, Serbia

    Vladimir L. Jakovljevic, Vladimir I. Zivkovic, Ivan M. Srejovic & Nevena S. Barudzic

  3. Department of Chemistry, Faculty of Science, University of Kragujevac, Radoja Domanovica 60, 34000, Kragujevac, Serbia

    Zivadin D. Bugarcic

  4. School of Medicine, Institute of Medical Physiology ‘‘Richard Burian’’, University of Belgrade, Visegradska 26/II, 11000, Belgrade, Serbia

    Dragan M. Djuric

  5. Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000, Kragujevac, Serbia

    Slobodan S. Novokmet

Authors
  1. Miroslav M. Misic
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  2. Vladimir L. Jakovljevic
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  3. Zivadin D. Bugarcic
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  4. Vladimir I. Zivkovic
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  5. Ivan M. Srejovic
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  6. Nevena S. Barudzic
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  7. Dragan M. Djuric
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  8. Slobodan S. Novokmet
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Corresponding author

Correspondence to Slobodan S. Novokmet.

Additional information

On the occasion of Prof. Dr. Zivadin D. Bugarcic 60th birthday.

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Misic, M.M., Jakovljevic, V.L., Bugarcic, Z.D. et al. Platinum Complexes-Induced Cardiotoxicity of Isolated, Perfused Rat Heart: Comparison of Pt(II) and Pt(IV) Analogues Versus Cisplatin. Cardiovasc Toxicol 15, 261–268 (2015). https://doi.org/10.1007/s12012-014-9293-8

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  • DOI: https://doi.org/10.1007/s12012-014-9293-8

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