title: gamma-Glutamylcysteine ethyl ester for myocardial protection in dogs during ischemia and reperfusion.
abstract: OBJECTIVE
  The aim of this study was to examine the infarct-limiting effects of gamma-glutamylcysteine ethyl ester, a newly discovered synthetic precursor of glutathione biosynthesis, in a canine model of myocardial infarction.
  
  
  BACKGROUND
  Reduced glutathione plays an important role in protecting cells against damage induced by reactive oxygen species during myocardial ischemia and reperfusion. Gamma-glutamylcysteine ethyl ester is capable of penetrating into cells in its intact form and increasing intracellular glutathione levels.
  
  
  METHODS
  Dogs were subjected to a 90-min coronary occlusion followed by 5 h of reperfusion. An intravenous bolus injection of gamma-glutamylcysteine ethyl ester (3 or 10 mg/kg body weight) was administered immediately before reperfusion. Regional myocardial blood flow was measured with the use of colored microspheres.
  
  
  RESULTS
  Gamma-glutamylcysteine ethyl ester effectively reduced infarct size in a dose-dependent manner (mean +/- SEM 26.4 +/- 3.5% in the low dose group [3 mg/kg, n = 10] and 19.0 +/- 3.4% in the high dose group [10 mg/kg, n = 10]; each p < 0.05 vs. the value in the control group [40.6 +/- 4.8%, n = 10]). There were no differences between the control and treated groups in hemodynamic variables or regional myocardial blood flow either during the ischemic period or after reperfusion. The reduced glutathione content of ischemic myocardium in the control group (0.62 +/- 0.11 mumol/g, p < 0.01) was significantly lower than that in nonischemic myocardium (1.46 +/- 0.07 mumol/g), and it was preserved by treatment in a dose-dependent manner (3 mg/kg, 0.83 +/- 0.06 mumol/g; 10 mg/kg, 0.92 +/- 0.14 mumol/g; each p < 0.05 vs. control level). There were no differences in oxidized glutathione content between nonischemic and ischemic myocardium or among the three groups.
  
  
  CONCLUSIONS
  Gamma-glutamylcysteine ethyl ester, a precursor of glutathione, significantly attenuates myocardial ischemia and reperfusion injury when administered immediately before reperfusion.
authors.affiliation: First Department of Medicine, Osaka University School of Medicine, Suita, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Hoshida
authors.forename: T
authors.initials: T
authors.lastname: Kuzuya
authors.forename: N
authors.initials: N
authors.lastname: Yamashita
authors.forename: M
authors.initials: M
authors.lastname: Nishida
authors.forename: S
authors.initials: S
authors.lastname: Kitahara
authors.forename: M
authors.initials: M
authors.lastname: Hori
authors.forename: T
authors.initials: T
authors.lastname: Kamada
authors.forename: M
authors.initials: M
authors.lastname: Tada
mesh_terms: D000818:Animals; D003326:Coronary Circulation / Q000502:physiology; D004151:Dipeptides / Q000008:administration & dosage / Q000627:therapeutic use*; D004285:Dogs; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D007275:Injections, Intravenous; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000517:prevention & control*; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D013997:Time Factors
chemical_list: D004151:Dipeptides; C067744:N-gamma-glutamylcysteine ethyl ester; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005978:Glutathione