Hydrogen Peroxide Production by Monoamine Oxidase during Ischemia-Reperfusion in the Rat Brain

Monoamine oxidase (MAO) as a source of hydrogen peroxide (H 2 O 2 ) was evaluated during ischemiareperfusion in vivo in the rat brain. H 2 O 2 production was assessed with and without inhibition of MAO during and after 15 min of ischemia. Metabolism of H 2 O 2 by catalase during ischemia and reperfusion was measured in forebrain homogenates using aminotriazole (ATZ), an irreversible H 2 O 2 -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 H 2 O 2 production decreased as measured at the microperoxisome. During reperfusion, a rapid increase in H 2 O 2 generation occurred within 5 min as measured by a threefold increase in oxidized glutathione (GSSG). The H 2 O 2 -dependent rates of ATZ inactivation of catalase between control and ischemia–reperfusion were similar, indicating that H 2 O 2 was more available to glutathione peroxidase than to catalase in this model. MAO inhibitors eliminated the biochemical indications of increased H 2 O 2 production and increased the catecholamine concentrations. Mortality was 67% at 48 h after ischemiareperfusion, and there was no improvement in survival after inhibition of MAO. We conclude that MAO is an important source of H 2 O 2 generation early in brain reperfusion, but inhibition of the enzyme does not improve survival in this model despite ablating H 2 O 2 production.