Murugan Ponniah Senthil, Selvam Govindan Sadasivam
Department of Biochemistry, School of Biological Sciences, Madurai Kamaraj University, Madurai, Tamil Nadu, India.
Toxicol Int. 2014 Jan;21(1):1-7. doi: 10.4103/0971-6580.128781.
Potassium ion (K(+)) plays an essential role in maintaining the electrical potential across the plasma membrane of cells. An abnormal serum K(+) level is associated with increased risk of ventricular arrhythmia and sudden cardiac death (SCD) and these patients are generally prescribed with furosemide and potassium chloride (KCl). We explored the association between the use of these drugs and the risk of SCD by analyzing biochemical parameters and proteomic changes.
The rats were administered with furosemide and KCl and their effect was analyzed by studying cardiac and oxidative markers, electrolyte content and histopathology. Two-dimensional gel electrophoresis (2-DE) and electrospray ionization-mass spectrometry were performed to investigate the LV proteomic changes.
Furosemide and KCl treatments showed significant effect on physiological and biochemical parameters, and LV histopathology of experimental rats. Proteomic analysis indicated 17 differentially expressed proteins. Among them, eight protein spots were identified using peptide mass fingerprinting. In furosemide-treated group, four proteins were upregulated and two proteins were downregulated when compared to 2-DE proteomic profile of control. While in KCl-treated rats, seven proteins were found downregulated.
[corrected] The present study revealed the differential expression of proteins by furosemide and KCl treatment. Thus, the results suggest that the use of these drugs leads to proteomic alteration, which involve in cardiac conductivity that might increase the risk of SCD.
钾离子（K⁺）在维持细胞跨质膜的电势方面起着至关重要的作用。血清钾离子水平异常与室性心律失常和心源性猝死（SCD）风险增加相关，这些患者通常会被开具呋塞米和氯化钾（KCl）。我们通过分析生化参数和蛋白质组学变化来探究这些药物的使用与SCD风险之间的关联。
给大鼠施用呋塞米和KCl，并通过研究心脏和氧化标志物、电解质含量及组织病理学来分析其效果。进行二维凝胶电泳（2-DE）和电喷雾电离质谱分析以研究左心室蛋白质组学变化。
呋塞米和KCl处理对实验大鼠的生理生化参数及左心室组织病理学有显著影响。蛋白质组学分析表明有17种差异表达蛋白。其中，通过肽质量指纹图谱鉴定出8个蛋白斑点。与对照组的2-DE蛋白质组图谱相比，在呋塞米处理组中，有4种蛋白上调，2种蛋白下调。而在KCl处理的大鼠中，发现有7种蛋白下调。
本研究揭示了呋塞米和KCl处理导致的蛋白质差异表达。因此，结果表明这些药物的使用会导致蛋白质组改变，这涉及心脏传导性，可能会增加SCD风险。
