Superiority of zinc complex of acetylsalicylic acid to acetylsalicylic acid in preventing postischemic myocardial dysfunction

Sevil Korkmaz, Ayhan Atmanli, Shiliang Li, Tamás Radovits, Peter Hegedűs, Enikő Barnucz, Kristóf Hirschberg, Sivakkanan Loganathan, Yutaka Yoshikawa, Hiroyuki Yasui, Matthias Karck, Gábor Szabó

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Abstract

The pathophysiology of ischemic myocardial injury involves cellular events, reactive oxygen species, and an inflammatory reaction cascade. The zinc complex of acetylsalicylic acid (Zn(ASA)2) has been found to possess higher anti-inflammatory and lower ulcerogenic activities than acetylsalicylic acid (ASA). Herein, we studied the effects of both ASA and Zn(ASA)2 against acute myocardial ischemia. Rats were pretreated with ASA (75 mg/kg) or Zn(ASA)2 (100 mg/kg) orally for five consecutive days. Isoproterenol (85 mg/kg, subcutaneously [s.c.]) was applied to produce myocardial infarction. After 17–22 h, animals were anesthetized with sodium pentobarbital (60 mg/kg, intraperitoneally [i.p.]) and both electrical and mechanical parameters of cardiac function were evaluated in vivo. Myocardial histological and gene expression analyses were performed. In isoproterenoltreated rats, Zn(ASA)2 treatment normalized significantly impaired left-ventricular contractility index (Emax 2.6 ± 0.7mmHg/mL vs. 4.6 ± 0.5 mmHg/mL, P<0.05), increased stroke volume (30 ± 3 mL vs. 50 ± 6 mL, P<0.05), decreased systemic vascular resistance (7.2 ± 0.7 mmHg/min/mL vs. 4.2 ± 0.5 mmHg/min/mL, P<0.05) and reduced inflammatory infiltrate into the myocardial tissues. ECG revealed a restoration of elevated ST-segment (0.21 ± 0.03mV vs. 0.09 ± 0.02 mV, P<0.05) and prolonged QT-interval (79.2 ± 3.2ms vs. 69.5 ± 2.5 ms, P<0.05) by Zn(ASA)2. ASA treatment did not result in an improvement of these parameters. Additionally, Zn(ASA)2 significantly increased the mRNA-expression of superoxide dismutase 1 (+73 ± 15%), glutathione peroxidase 4 (+44 ± 12%), and transforming growth factor (TGF)-β1 (+102 ± 22%). In conclusion, our data demonstrate that oral administration of zinc and ASA in the form of bis(aspirinato)zinc(II) complex is superior to ASA in preventing electrical, mechanical, and histological changes after acute myocardial ischemia. The induction of antioxidant enzymes and the anti-inflammatory cytokine TGF-β1 may play a pivotal role in the mechanism of action of Zn(ASA)2.

Original languageEnglish
Pages (from-to)1247-1255
Number of pages9
JournalExperimental Biology and Medicine
Volume240
Issue number9
DOIs
Publication statusPublished - Jan 1 2015

Keywords

  • Acetylsalicylic acid
  • Antioxidant
  • Cardiac function
  • Isoproterenol
  • Myocardial ischemia
  • Zinc complex of acetylsalicylic acid

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Korkmaz, S., Atmanli, A., Li, S., Radovits, T., Hegedűs, P., Barnucz, E., Hirschberg, K., Loganathan, S., Yoshikawa, Y., Yasui, H., Karck, M., & Szabó, G. (2015). Superiority of zinc complex of acetylsalicylic acid to acetylsalicylic acid in preventing postischemic myocardial dysfunction. Experimental Biology and Medicine, 240(9), 1247-1255. https://doi.org/10.1177/1535370215570184