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Original Article

Korean Journal of Physiology and Pharmacology 2019; 23(3): 203-217

Published online May 1, 2019 https://doi.org/10.4196/kjpp.2019.23.3.203

Copyright © Korean J Physiol Pharmacol.

Effects of heme oxygenase-1 upregulation on isoproterenol-induced myocardial infarction

Somaia A.G. Eltobshy1, Abdelaziz M. Hussein1,*, Asaad A. Elmileegy1, Mona H. Askar1, Yomna Khater2, Emile F. Metias1, and Ghada M. Helal3

1Department of Physiology, 2Medical Experimental Research Center, and 3Department of Medical Biochemistry, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The present study was designed to examine the effect of heme oxygenase-1 (HO-1) induction by cobalt protoporphyrin (CoPP) on the cardiac functions and morphology, electrocardiogram (ECG) changes, myocardial antioxidants (superoxide dismutase [SOD] and glutathione [GSH]), and expression of heat shock protein (Hsp) 70 and connexin 43 (Cx-43) in myocardial muscles in isoproterenol (ISO) induced myocardial infarction (MI). Thirty two adult male Sprague Dawely rats were divided into 4 groups (each 8 rats): normal control (NC) group, ISO group: received ISO at dose of 150 mg/kg body weight intraperitoneally (i.p.) for 2 successive days; ISO + Trizma group: received (ISO) and Trizma (solvent of CoPP) at dose of 5 mg/kg i.p. injection 2 days before injection of ISO, with ISO at day 0 and at day 2 after ISO injections; and ISO + CoPP group: received ISO and CoPP at a dose of 5 mg/kg dissolved in Trizma i.p. injection as Trizma. We found that, administration of ISO caused significant increase in heart rate, corrected QT interval, ST segment, cardiac enzymes (lactate dehydrogenase, creatine kinase-muscle/brain), cardiac HO-1, Hsp70 with significant attenuation in myocardial GSH, SOD, and Cx-43. On the other hand, administration of CoPP caused significant improvement in ECG parameters, cardiac enzymes, cardiac morphology; antioxidants induced by ISO with significant increase in HO-1, Cx-43, and Hsp70 expression in myocardium. In conclusions, we concluded that induction of HO-1 by CoPP ameliorates ISO-induced myocardial injury, which might be due to up-regulation of Hsp70 and gap junction protein (Cx-43).

Keywords: Connexin 43, Heme oxygenase-1, HSP70 heat-shock proteins, Isoproterenol-myocardial infarction