Administration of zinc complex of acetylsalicylic acid after the onset of myocardial injury protects the heart by upregulation of antioxidant enzymes.
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.
Department of Cardiac Surgery, University of Heidelberg, INF 326 (2. OG), 69120, Heidelberg, Germany. korkmaz@uni-heidelberg.de.
Sevil
S
Korkmaz-Icöz
Department of Cardiac Surgery, University of Heidelberg, INF 326 (2. OG), 69120, Heidelberg, Germany.
Ayhan
A
Atmanli
Heart and Vascular Center, Semmelweis University, 1122, Budapest, Hungary.
Tamás
T
Radovits
Department of Cardiac Surgery, University of Heidelberg, INF 326 (2. OG), 69120, Heidelberg, Germany.
Shiliang
S
Li
Department of Cardiac Surgery, University of Heidelberg, INF 326 (2. OG), 69120, Heidelberg, Germany.
Peter
P
Hegedüs
Department of Cardiac Surgery, University of Heidelberg, INF 326 (2. OG), 69120, Heidelberg, Germany.|Heart and Vascular Center, Semmelweis University, 1122, Budapest, Hungary.
Mihály
M
Ruppert
Department of Cardiac Surgery, University of Heidelberg, INF 326 (2. OG), 69120, Heidelberg, Germany.
Paige
P
Brlecic
Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, Kyoto, 607-8414, Japan.
Yutaka
Y
Yoshikawa
Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, Kyoto, 607-8414, Japan.
Hiroyuki
H
Yasui
Department of Cardiac Surgery, University of Heidelberg, INF 326 (2. OG), 69120, Heidelberg, Germany.
Matthias
M
Karck
Department of Cardiac Surgery, University of Heidelberg, INF 326 (2. OG), 69120, Heidelberg, Germany.
Gábor
G
Szabó
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001241:Aspirin / Q000008:administration & dosage*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006335:Heart Injuries / Q000188:drug therapy* / Q000378:metabolism; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D015854:Up-Regulation / Q000187:drug effects*; D015032:Zinc / Q000008:administration & dosage*
D000975:Antioxidants; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D005979:Glutathione Peroxidase; C523860:glutathione peroxidase 4, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000254:Sodium-Potassium-Exchanging ATPase; D015032:Zinc; D001241:Aspirin
Isoproterenol; Myocardial ischemia; Zinc complex of acetylsalicylic acid