Effect of glutathione monoethyl ester on glutathione level and cardiac energetics in reperfused pig heart.
The GSH level in myocardial tissue represents an important defense mechanism against oxygen toxicity. Since the ischemia-induced depletion of GSH might favour the cytotoxicity of oxygen-derived free radicals produced during reperfusion, we assessed the effects of the GSH donor, glutathione monoethylester, in anaesthetized pigs subjected to 90 minutes of coronary occlusion followed by 30 minutes reperfusion. The drug was infused intracoronarily at a dose of 1 mg/ml (0.5 ml/min) throughout the experimental period. After coronary occlusion and reperfusion, we found a decrease in GSH, ADP, ATP and phosphocreatine levels in reperfused compared with non-ischemic tissue. Less evident were the differences in mitochondrial function, there being only a reduction in the reperfused tissue of the respiratory control index and state 3 respiration values when pyruvate was used as substrate. The infusion with glutathione monoethylester decreased the depletion of tissue GSH and improved the GSH/GSSG ratio, particularly in the non-ischemic tissue. Moreover, the drug decreased the mitochondrial dysfunction at the level of pyruvate utilization and partially prevented the fall in ATP in the reperfused tissue. This study confirms a possible protective effect of glutathione monoethylester in the prevention of reperfusion-induced myocardial damage.
Guarnieri
C
C
Department of Biochemistry G. Moruzzi, University of Bologna, Italy.
Turinetto
B
B
Colì
G
G
Muscari
C
C
Cattabriga
I
I
Vaona
I
I
Finelli
C
C
Pigini
F
F
Caldarera
C M
CM
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D005260:Female; D005609:Free Radicals; D005978:Glutathione / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism*; D013552:Swine
D005609:Free Radicals; D010725:Phosphocreatine; D000244:Adenosine Diphosphate; C042431:S-ethyl glutathione; D000255:Adenosine Triphosphate; D005978:Glutathione