<abstract xmlns="http://www.w3.org/1999/xhtml">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.</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.

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

Institute of Medical Physiology “Richard Burian”

Experimental and Applied Biomedical Research (EABR)

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

{"article-title":"The Platinum(II) Complexes Induced Oxidative Stress of Isolated Rat Heart"}

Interest for the clinical application of transition metal complexes as chemotherapeutic agents initially started with discovery of cisplatin. Despite the...

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

Publié en ligne: 29 mai 2017

Pages: 111 - 117

Reçu: 04 juil. 2016

Accepté: 26 juil. 2016

DOI: https://doi.org/10.1515/sjecr-2016-0059

Mots clés
cisplatin, 1,2-diaminocyclohexane, isolated rat heart, oxidative stress, perfusion, platinum(II) complexes

© 2017 Katarina Radonjic et al., published by De Gruyter Open

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

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

Publié en ligne: 29 mai 2017

Pages: 111 - 117

Reçu: 04 juil. 2016

Accepté: 26 juil. 2016

DOI: https://doi.org/10.1515/sjecr-2016-0059

Mots cléscisplatin, 1,2-diaminocyclohexane, isolated rat heart, oxidative stress, perfusion, platinum(II) complexes

© 2017 Katarina Radonjic et al., published by De Gruyter Open

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Mots clés
cisplatin, 1,2-diaminocyclohexane, isolated rat heart, oxidative stress, perfusion, platinum(II) complexes