Administration of zinc complex of acetylsalicylic acid after the onset of myocardial injury protects the heart by upregulation of antioxidant enzymes

J Physiol Sci. 2016 Mar;66(2):113-25. doi: 10.1007/s12576-015-0403-6. Epub 2015 Oct 23.

Abstract

We recently demonstrated that the pre-treatment of rats with zinc and acetylsalicylic acid complex in the form of bis(aspirinato)zinc(II) [Zn(ASA)2] is superior to acetylsalicylic acid in protecting the heart from acute myocardial ischemia. Herein, we hypothesized that Zn(ASA)2 treatment after the onset of an acute myocardial injury could protect the heart. The rats were treated with a vehicle or Zn(ASA)2 after an isoproterenol injection. Isoproterenol-induced cardiac damage [inflammatory infiltration into myocardial tissue, DNA-strand breakage evidenced by TUNEL-assay, increased 11-dehydro thromboxane (TX)B2-levels, elevated ST-segment, widened QRS complex and prolonged QT-interval] was prevented by the Zn(ASA)2 treatment. In isoproterenol-treated rats, load-independent left ventricular contractility parameters were significantly improved after Zn(ASA)2. Furthermore, Zn(ASA)2 significantly increased the myocardial mRNA-expression of superoxide dismutase-1, glutathione peroxidase-4 and decreased the level of Na(+)/K(+)/ATPase. Postconditioning with Zn(ASA)2 protects the heart from acute myocardial ischemia. Its mechanisms of action might involve inhibition of pro-inflammatory prostanoids and upregulation of antioxidant enzymes.

Keywords: Isoproterenol; Myocardial ischemia; Zinc complex of acetylsalicylic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / metabolism*
  • Aspirin / administration & dosage*
  • Glutathione Peroxidase / metabolism
  • Heart Injuries / drug therapy*
  • Heart Injuries / metabolism
  • Heart Ventricles / drug effects*
  • Heart Ventricles / metabolism
  • Male
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / metabolism
  • Myocardium / metabolism
  • Phospholipid Hydroperoxide Glutathione Peroxidase
  • Rats
  • Rats, Sprague-Dawley
  • Sodium-Potassium-Exchanging ATPase / metabolism
  • Superoxide Dismutase / metabolism
  • Superoxide Dismutase-1
  • Up-Regulation / drug effects*
  • Zinc / administration & dosage*

Substances

  • Antioxidants
  • Phospholipid Hydroperoxide Glutathione Peroxidase
  • Glutathione Peroxidase
  • glutathione peroxidase 4, rat
  • Superoxide Dismutase
  • Superoxide Dismutase-1
  • Sodium-Potassium-Exchanging ATPase
  • Zinc
  • Aspirin