Vascular Biology Lab, SASTRA University, Thanjavur, Tamilnadu, 613401, India.
School of chemical and biotechnology, SASTRA University, Thanjavur, Tamilnadu, 613401, India.
Cardiovasc Drugs Ther. 2017 Dec;31(5-6):511-524. doi: 10.1007/s10557-017-6751-0.
Sodium thiosulfate (STS) has of late been proven efficacious in models of urolithiasis and vascular calcification. However, its cardiovascular effects on ischemia reperfusion injury (IR) have not been revealed. Being an antioxidant and calcium chelator, it is assumed to play a vital role in IR as ROS production and calcium overload are major perpetrators of IR injury.
The cardioprotective effect of STS was evaluated in vitro using H9C2 cardiomyocytes and in vivo using both isolated rat heart and intact left anterior descending artery (LAD) occlusion models of ischemia reperfusion injury. Finally, in silico tools were utilized to establish its possible mode of action. Myocardial injury markers and expression of apoptotic proteins were studied along with myocardial histopathology.
STS of 1 mM recovered H9C2 cells from glucose oxidase/catalase-induced apoptosis. The isolated rat heart treated with STS prior to IR injury improved its hemodynamics and reduced the infarct size to 9%. This was supported by the absence of derangement of cardiac fibers from H&E stained section of LAD-occluded rats. Plasma troponin levels decreased by 15% compared to IR and the myocardium showed diminished apoptotic proteins. An in silico docking analysis revealed higher binding affinity of STS for caspase-3 with a binding energy of - 60.523 kcal/mol for the complex.
The effectiveness of STS as a cardioprotective agent is attributed to the reduction of apoptosis by binding to the active site of caspase-3 in silico, which was substantiated by the reduced expression of caspase-3 and poly ADP ribose polymerase levels.
硫代硫酸钠（STS）最近已被证明在尿石症和血管钙化模型中有效。然而，其对缺血再灌注损伤（IR）的心血管影响尚未揭示。作为一种抗氧化剂和钙螯合剂，人们认为它在 IR 中起着至关重要的作用，因为 ROS 产生和钙超载是 IR 损伤的主要原因。
在体外使用 H9C2 心肌细胞和体内使用离体大鼠心脏和完整左前降支（LAD）闭塞缺血再灌注损伤模型评估 STS 的心脏保护作用。最后，利用计算机模拟工具确定其可能的作用模式。研究了心肌损伤标志物和凋亡蛋白的表达以及心肌组织病理学。
1mM 的 STS 使葡萄糖氧化酶/过氧化氢酶诱导的 H9C2 细胞从凋亡中恢复。在 IR 损伤前用 STS 处理的离体大鼠心脏改善了其血液动力学，并将梗塞面积缩小到 9%。这得到了 LAD 闭塞大鼠 H&E 染色切片中没有心脏纤维紊乱的支持。与 IR 相比，血浆肌钙蛋白水平降低了 15%，心肌中凋亡蛋白减少。计算机对接分析显示 STS 与 caspase-3 的结合亲和力更高，复合物的结合能为-60.523 kcal/mol。
STS 作为一种心脏保护剂的有效性归因于通过计算机模拟与 caspase-3 的活性位点结合减少凋亡，这得到了 caspase-3 和聚 ADP 核糖聚合酶水平降低的证实。
