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顺铂和顺铂结构类似物对离体大鼠心脏的灌注:对冠脉血流和心脏动力学参数的影响。

The perfusion of cisplatin and cisplatin structural analogues through the isolated rat heart: The effects on coronary flow and cardiodynamic parameters.

作者信息

Stojic Isidora M, Jakovljevic Vladimir Lj, Zivkovic Vladimir I, Srejovic Ivan M, Nikolic Tamara R, Jeremic Jovana N, Jeremic Nevena S, Djuric Dragan M, Radonjic Katarina G, Labudovic-Borovic Milica, Bugarcic Zivadin D, Bogojeski Jovana, Novokmet Slobodan S

机构信息

Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Serbia.

出版信息

Gen Physiol Biophys. 2018 Sep;37(5):515-525. doi: 10.4149/gpb_2018004.

Abstract

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.

摘要

顺铂用于治疗实体瘤时会产生器官毒性。其中,心脏毒性是一种偶发但非常严重的副作用。为了预防或减少这些负面影响,人们合成了许多顺铂类似物,并对其作为毒性更小、效果更佳的药物进行了评估。在本研究中,我们检测了顺铂及其三种类似物对离体大鼠心脏的影响,以确定铂配合物结构的变化(载体配体的改变——乙二胺;1,2 - 二氨基环己烷;2,2':6',2'' - 三联吡啶)是否会影响其心脏毒性作用。我们的研究结果表明,在铂配合物结构中引入芳香环会对心脏功能产生负面影响。相反,与顺铂相比,另外两种检测的配合物对心脏功能的负面影响较小。我们的发现可能对引入具有较小心脏毒性作用的载体配体的合成策略具有参考价值。

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