Hydrogen peroxide production by monoamine oxidase during ischemia-reperfusion in the rat brain.
Monoamine oxidase (MAO) as a source of hydrogen peroxide (H2O2) was evaluated during ischemia-reperfusion in vivo in the rat brain. H2O2 production was assessed with and without inhibition of MAO during and after 15 min of ischemia. Metabolism of H2O2 by catalase during ischemia and reperfusion was measured in forebrain homogenates using aminotriazole (ATZ), an irreversible H2O2-dependent inhibitor of catalase. Catecholamine and glutathione concentrations in forebrain were measured with and without MAO inhibitors. During ischemia, forebrain blood flow was reduced to 8% of baseline and H2O2 production decreased as measured at the microperoxisome. During reperfusion, a rapid increase in H2O2 generation occurred within 5 min as measured by a threefold increase in oxidized glutathione (GSSG). The H2O2-dependent rates of ATZ inactivation of catalase between control and ischemia-reperfusion were similar, indicating that H2O2 was more available to glutathione peroxidase than to catalase in this model. MAO inhibitors eliminated the biochemical indications of increased H2O2 production and increased the catecholamine concentrations. Mortality was 67% at 48 h after ischemia-reperfusion, and there was no improvement in survival after inhibition of MAO. We conclude that MAO is an important source of H2O2 generation early in brain reperfusion, but inhibition of the enzyme does not improve survival in this model despite ablating H2O2 production.
Simonson
S G
SG
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
Zhang
J
J
Canada
A T
AT
Su
Y F
YF
Benveniste
H
H
Piantadosi
C A
CA
D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism*
D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D002374:Catalase; D008995:Monoamine Oxidase; D005978:Glutathione; D000640:Amitrole