Effects of N-acetylcysteine in the rat heart reperfused after low-flow ischemia: evidence for a direct scavenging of hydroxyl radicals and a nitric oxide-dependent increase in coronary flow.
The capacity of N-acetylcysteine to directly scavenge hydroxyl radical produced by rat hearts reperfused after 90 min of low-flow ischemia was assessed by the hydroxylation of 4-hydroxybenzoate into 3,4-dihydroxybenzoate using a gas chromatography-mass spectrometric assay. Reperfused hearts showed a massive release of 3,4-dihydroxybenzoate, lactate dehydrogenase, and total glutathione, contained less reduced and oxidized glutathione, but maintained spontaneous beating and coronary flow rates close to preischemic values. Compared to untreated hearts: reperfused hearts treated with N-acetylcysteine from the start of ischemia (i) released four times less 3,4-dihydroxybenzoate, but similar amounts of lactate dehydrogenase or glutathione, (ii) showed a nitric oxide-dependent increase in coronary flow rate, and (iii) contained less oxidized glutathione, but similar amounts of reduced glutathione. Reperfused hearts receiving N-acetylcysteine since the last 5 min of ischemia had also a four-times lower 3,4-dihydroxybenzoate release, but their coronary flow rate response was similar to that of untreated hearts. These results indicate that N-acetylcysteine can directly scavenge hydroxyl radicals produced by reperfused ischemic hearts, although this effect is not associated with any protective effects as indicated by the lactate dehydrogenase and glutathione release and cannot explain the nitric oxide-dependent reperfusion hyperemia.
Department of Nutrition, University of Montréal, Québec, Canada.
J
J
Brunet
M J
MJ
Boily
S
S
Cordeau
C
C
Des Rosiers
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism; D019803:Glutathione Disulfide; D006321:Heart / Q000187:drug effects; D062385:Hydroxybenzoates / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D016166:Free Radical Scavengers; D062385:Hydroxybenzoates; D009569:Nitric Oxide; D017665:Hydroxyl Radical; C009091:protocatechuic acid; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; D019803:Glutathione Disulfide; D000111:Acetylcysteine