Key result
Perfusion with [Pt(terpy)Cl]Cl induced a significantly greater decrease in cardiodynamic parameters and coronary flow compared to cisplatin, while [Pt(en)Cl2] and [Pt(dach)Cl2] showed less cardiotoxicity.
Structural modification of cisplatin by introducing specific carrier ligands can reduce its cardiotoxic effects in an isolated rat heart model.
The therapeutic use of cisplatin for the treatment of solid tumours is associated with organ toxicity. Amongst those, the cardiotoxicity is an occasional but very serious and severe side effect. To prevent or reduce these negative effects, many cisplatin analogues have been synthesized and evaluated in terms of being a less toxic and more effective agent. In present study, we examined the effects of cisplatin and its three analogues in the isolated rat heart to determine whether changes in the structure of the platinum complexes (changing of carrier ligands - ethylenediamine; 1,2-diaminocyclohexane; 2,2':6',2''-terpyridine) can influence their cardiotoxic effects. The results of our research indicate that the introduction of aromatic rings in the structure of the platinum complexes has a negative influence on the heart function. Conversely, the other two examined complexes had less negative effects on heart function compared to cisplatin. Our findings may be of interest for a possible synthetic strategy of introducing a carrier ligand that will exert a less cardiotoxic effect.
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Stojić et al. (2018) studied Cardiotoxicity (n=180). Cisplatin and structural analogues ([Pt(en)Cl2], [Pt(dach)Cl2], [Pt(terpy)Cl]Cl) vs. Krebs-Henseleit solution was evaluated on Cardiodynamic parameters and coronary flow (p=<0.05). Perfusion with [Pt(terpy)Cl]Cl induced a significantly greater decrease in cardiodynamic parameters and coronary flow compared to cisplatin, while [Pt(en)Cl2] and [Pt(dach)Cl2] showed less cardiotoxicity.
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