Toxicology International

Furosemide and Potassium Chloride‑induced Alteration in Protein Profile of Left Ventricle and its Associated Risk for Sudden Cardiac Death


Affiliations

  • School of Biological Sciences, Madurai Kamaraj University, Department of Biochemistry, Madurai, Tamil Nadu, India

Abstract

Background: 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. Materials and Methods: 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. Results: 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. Conculsion: 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.

Keywords

Cardiac conductivity, proteomic alteration, sudden cardiac death

Full Text:

References

Francis J. Prevention of sudden cardiac death. Indian Pacing Electrophysiol J 2011;11:91‑2.

Chugh SS, Jui J, Gunson K, Stecker EC, John BT, Thompson B, et al. Current burden of sudden cardiac death: Multiple source surveillance versus retrospective death certificate‑based review in a large U.S. community. J Am Coll Cardiol 2004;44:1268‑75.

Russo P, Barba G, Venezia A, Siani A. Dietary potassium in cardiovascular prevention: Nutritional and clinical implications. Curr Med Chem‑Immun Endoc and Metab Agents 2005;5:21‑31.

Maeder M, Rickli H, Sticherling C, Widmer R, Ammann P. Hypokalaemia and sudden cardiac death‑lessons from implantable cardioverter defibrillators. Emerg Med J 2007;24:206‑8.

Vanden Hoek TL, Morrison LJ, Shuster M, Donnino M, Sinz E, Lavonas EJ, et al. Part 12: Cardiac arrest in special situations: 2010 American heart association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 2010;122:S829‑61.

Rokutan H, Suckow C, von Haehling S, Strassburg S, Bockmeyer B, Doehner W, et al. Furosemide induces mortality in a rat model of chronic heart failure. Int J Cardiol 2012;160:20‑5.

McCurley JM, Hanlon SU, Wei SK, Wedam EF, Michalski M, Haigney MC. Furosemide and the progression of left ventricular dysfunction in experimental heart failure. J Am Coll Cardiol 2004;44:1301‑7.

Remme WJ, Swedberg K; Task Force for the Diagnosis and Treatment of Chronic Heart Failure, European Society of Cardiology. Guidelines for the diagnosis and treatment of chronic heart failure. Eur Heart J 2001;22:1527‑60.

He FJ, Marciniak M, Carney C, Markandu ND, Anand V, Fraser WD, et al. Effects of potassium chloride and potassium bicarbonate on endothelial function, cardiovascular risk factors, and bone turnover in mild hypertensives. Hypertension 2010;55:681‑8.

Martinez DV, Rocha R, Matsumura M, Oestreicher E, Ochoa‑Maya M, Roubsanthisuk W, et al. Cardiac damage prevention by eplerenone: Comparison with low sodium diet or potassium loading. Hypertension 2002;39:614‑8.

Kuwahara M, Chiku K, Shiono T, Tsubone H, Sugano S. ECG changes under hyperkalemia with nephrectomy in the rat. J Electrocardiol 1992;25:215‑9.

Shieh CC, Coghlan M, Sullivan JP, Gopalakrishnan M. Potassium channels: Molecular defects, diseases, and therapeutic opportunities. Pharmacol Rev 2000;52:557‑94.

McGregor E, Dunn MJ. Proteomics of the heart: Unraveling disease. Circ Res 2006;98:309‑21.

Zhu D, Deng XW. A non‑coding RNA locus mediates environment‑conditioned male sterility in rice. Cell Res 2012;22:791‑2.

Neuhoff V, Arold N, Taube D, Ehrhardt W. Improved staining of proteins in polyacrylamide gels including isoelectric focusing gels with clear background at nanogram sensitivity using Coomassie Brilliant Blue G‑250 and R‑250. Electrophoresis 1988;9:255‑62.

Ananthi S, Chitra T, Bini R, Prajna NV, Lalitha P, Dharmalingam K.Comparative analysis of the tear protein profile in mycotic keratitis patients. Mol vis 2008;14:500‑7.

McEvoy GK. (ed.) American hospital formulary service‑Drug information. Bethesda, MD: American Society of Health‑System Pharmacists, Inc; 2002 (Plus Supplements). p. 2568‑9.

Norman GJ, Morris JS, Karelina K, Weil ZM, Zhang N, Al‑Abed Y, et al. Cardiopulmonary arrest and resuscitation disrupts cholinergic anti‑inflammatory processes: A role for cholinergic α7 nicotinic receptors. J Neurosci 2011;31:3446‑52.

El‑Sherif N, Turitto G. Electrolyte disorders and arrhythmogenesis.Cardiol J 2011;18:233‑45.

Stason WB, Cannon PJ, Heinemann HO, Laragh JH. Furosemide. A clinical evaluation of its diuretic action. Circulation 1966;34:910‑20.

Mount, DB, Zandi‑Nejad K. Disorders of potassium balance. In: Brenner and Rector’s The Kidney, 8st edn. Philadelphia: Saunders; 2008. p. 547‑87.

Simpson JA, Brunt KR, Collier CP, Iscoe S. Hyperinflation‑induced cardiorespiratory failure in rats. J Appl Physiol (1985) 2009;107:275‑82.

Rastergar A, Soleimani M. Hypokalaemia and hyperkalaemia. Postgrad Med J 2001;77:759‑64.

Murugan PS, Ramprasath T, Selvam GS. Cardioprotective role of Acalypha indica extract on Isoproterenol induced myocardial infarction in rats. J Pharm Res 2011;4:2129‑32.

Ivetic A, Ridley AJ. Ezrin/radixin/moesin proteins and Rho GTPase signaling in leucocytes. Immunology 2004;112:165‑76.

NCBI database. KCNG2 potassium voltage‑gated channel, subfamily G, member 2 [Homo sapiens (human)]. Available from: (http://www.ncbi.nlm.nih.gov/gene/26251). Gene ID: 26251 [Last updated on 2013 Mar 16, Last accessed on 2013 Mar 18].

Leonoudakis D, Conti LR, Radeke CM, McGuire LM, Vandenberg CA. A multiprotein trafficking complex composed of SAP97, CASK, Veli, and Mint1 is associated with inward rectifier Kir2 potassium channels. J Biol Chem 2004;279:19051‑63.

Jazii FR, Najafi Z, Malekzadeh R, Conrads TP, Ziaee AA, Abnet C, et al. Identification of squamous cell carcinoma associated proteins by proteomics and loss of beta tropomyosin expression in esophageal cancer. World J Gastroentrol 2006;12:7104‑12.

Cassar‑Malek I, Jurie C, Bernard C, Barnola I, Micol D, Hocquette JF. Pasture‑feeding of Charolais steers influences skeletal muscle metabolism and gene expression. J Physiol Pharmacol 2009;60:83‑90.

Prabhakar R, Boivin GP, Hoit B, Wieczorek DF. Rescue of high expression beta‑tropomyosin transgenic mice by 5‑propyl‑2‑thiouracil. Regulating the alpha‑myosin heavy chain promoter. J Biol Chem 1999;274:29558‑63.


Refbacks

  • There are currently no refbacks.