Rosic Gvozden, Selakovic Dragica, Joksimovic Jovana, Srejovic Ivan, Zivkovic Vladimir, Tatalović Nikola, Orescanin-Dusic Zorana, Mitrovic Slobodanka, Ilic Milena, Jakovljevic Vladimir
Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Serbia.
Department of Physiology, Institute for Biological Research, University of Belgrade, Serbia.
Toxicol Lett. 2016 Feb 3;242:34-46. doi: 10.1016/j.toxlet.2015.11.028. Epub 2015 Nov 30.
The aim of this study was to evaluate the effects of chronic NAC administration along with cisplatin on cisplatin-induced cardiotoxicity by means of coronary flow (CF), cardiodynamic parameters, oxidative stress markers and morphological changes in isolated rat heart. Isolated hearts of Wistar albino rats (divided into four groups: control, cisplatin, NAC and cisplatin+NAC group) were perfused according to Langendorff technique at constant coronary perfusion pressure starting at 50 and gradually increased to 65, 80, 95 and 110 cm H2O to evaluate cardiodynamic parameters within autoregulation range. Samples of coronary venous effluent (CVE) were collected for determination of CF and biochemical assays, and heart tissue samples for biochemical assays and histopathological examination. Cisplatin treatment decreased CF and heart rate, and increased left ventricular systolic pressure and maximum left ventricular pressure development rate. Cisplatin increased H2O2 and TBARS, but decreased NO2(-) levels in CVE. In tissue samples, cisplatin reduced pathological alterations in myocardium and coronary vessels, with no changes in the amount of total glutathione, as well as in activity of glutathione peroxidase and glutathione reductase. NAC coadministration, by reducing oxidative damage, attenuated cisplatin-induced changes of cardiodynamic and oxidative stress parameters, as well as morphological changes in myocardium and coronary vasculature.
本研究的目的是通过冠状动脉血流量（CF）、心脏动力学参数、氧化应激标志物以及离体大鼠心脏的形态学变化，评估长期给予N-乙酰半胱氨酸（NAC）联合顺铂对顺铂诱导的心脏毒性的影响。将Wistar白化大鼠的离体心脏（分为四组：对照组、顺铂组、NAC组和顺铂+NAC组）按照Langendorff技术在恒定的冠状动脉灌注压力下进行灌注，起始压力为50 cm H2O，并逐渐增加至65、80、95和110 cm H2O，以评估自动调节范围内的心脏动力学参数。收集冠状静脉流出液（CVE）样本用于测定CF和生化分析，收集心脏组织样本用于生化分析和组织病理学检查。顺铂治疗降低了CF和心率，并增加了左心室收缩压和左心室最大压力上升速率。顺铂增加了CVE中的H2O2和硫代巴比妥酸反应物（TBARS），但降低了NO2(-)水平。在组织样本中，顺铂减少了心肌和冠状动脉血管的病理改变，总谷胱甘肽含量、谷胱甘肽过氧化物酶和谷胱甘肽还原酶的活性没有变化。联合给予NAC通过减少氧化损伤，减轻了顺铂诱导的心脏动力学和氧化应激参数变化以及心肌和冠状动脉血管的形态学变化。
