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

• Published in: The Korean journal of physiology & pharmacology Vol. 23; no. 3; pp. 203 - 217
• Main Authors: Eltobshy, Somaia A G, Hussein, Abdelaziz M, Elmileegy, Asaad A, Askar, Mona H, Khater, Yomna, Metias, Emile F, Helal, Ghada M
• Format: Journal Article
• Language: English
• Published: Korea (South) The Korean Physiological Society and The Korean Society of Pharmacology 01.05.2019
• Subjects: Original; Isoproterenol-myocardial infarction; Connexin 43; HSP70 heat-shock proteins; Heme oxygenase-1
• ISSN: 1226-4512; 2093-3827
• DOI: 10.4196/kjpp.2019.23.3.203

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).