Korean J Physiol Pharmacol.  2019 May;23(3):203-217. 10.4196/kjpp.2019.23.3.203.

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

Affiliations
  • 1Department of Physiology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt. menhag@mans.edu.eg
  • 2Medical Experimental Research Center, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.
  • 3Department of Medical Biochemistry, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.

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).

Keyword

Connexin 43; Heme oxygenase-1; HSP70 heat-shock proteins; Isoproterenol-myocardial infarction

MeSH Terms

Adult
Animals
Antioxidants
Body Weight
Cobalt
Connexin 43
Connexins
Creatine
Electrocardiography
Glutathione
Hand
Heart Rate
Heat-Shock Proteins
Heme Oxygenase-1*
Heme*
HSP70 Heat-Shock Proteins
Humans
Isoproterenol
Male
Muscles
Myocardial Infarction*
Myocardium
Oxidoreductases
Rats
Tromethamine
Up-Regulation*
Antioxidants
Cobalt
Connexin 43
Connexins
Creatine
Glutathione
HSP70 Heat-Shock Proteins
Heat-Shock Proteins
Heme
Heme Oxygenase-1
Isoproterenol
Oxidoreductases
Tromethamine
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