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

Abstract

Summary: Monoamine oxidase (MAO) as a source of hy drogen peroxide (H202) was evaluated during ischemia reperfusion in vivo in the rat brain. H202 production was assessed with and without inhibition of MAO during and after 15 min of ischemia. Metabolism of H202 by catalase during ischemia and reperfusion was measured in fore brain homogenates using aminotriazole (A TZ), an irre versible HzOz-dependent inhibitor of catalase. Catechol amine and glutathione concentrations in forebrain were measured with and without MAO inhibitors. During isch emia, forebrain blood flow was reduced to 8% of baseline and HzOz production decreased as measured at the mi croperoxisome. During reperfusion, a rapid increase in H20Z generation occurred within 5 min as measured by a threefold increase in oxidized glutathione (GSSG). The Abbreviations used: ANOVA, analysis of variance; ATZ, 3-amino-l,2,4-triazole; DTNB, 5,5' -dithiobis-(2-nitrobenzoic acid); GSH, reduced glutathione; GSSG, oxidized glutathione; MAO, monoamine oxidase; NEM, N-ethylmaleimide; ROS, re active oxygen species; SOD, superoxide dismutase. 125H202-dependent rates of A TZ inactivation of catalase be tween control and ischemia-reperfusion were similar, in dicating that H202 was more available to glutathione per oxidase than to catalase in this model. MAO inhibitors eliminated the biochemical indications of increased H20Z production and increased the catecholamine concentra tions. 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 H20Z generation early in brain reper fusion, but inhibition of the enzyme does not improve survival in this model despite ablating H202 production. Key Words: Reactive oxygen species-Central nervous system-Glutathione-Catalase-Catecholamines. To protect cells from damage by ROS, antioxi dant systems exist to detoxify these compounds.These systems include nonenzymatic "scavengers"

The Effect of Dexmedetomidine and Propofol on Oxidative Stress and Antioxidizing System Studied on Liver Ischemia-reperfusion Model on Rats

“…Simonson et al also have reported similar results [29]. In our study the level SOD was similar in both the dexmedetomidine group and the I/R group but the GPx levels were significantly higher in the dexmedetomidine group in respect to the I/R group.…”

“…Besides this direct effect, in series of I/R models on different tissue models, the free oxygen radicals produced by autooxidation end pruduct of the increased catecholamines may play a role in the tissue damage. Simonson et al have produced I/R injury on rat brain and have observed the increase in H 2 O 2 levels at the 5th minute of reperfusion and the reason for this increase was the oxidative deanimation of increased catecholamines by the monoamine oxidase (MAO) which increases in tissue by reperfusion [29]. Also in this study the level of oxidised glutathione was three times its normal value.…”

MAO‐B Inhibition by a Single Dose of l‐Deprenyl or Lazabemide Does Not Prevent Neuronal Damage Following Focal Cerebral Ischaemia in Rats

“…MAO inhibitors decrease free radical formation and thus could prevent cerebral damage (Matsui & Kumagae 1991;Simonson et al 1993;Suzuki et al 1995). To our knowledge, however, there are no data, on the possibility of MAO-B inhibitors being protective in focal cerebral ischaemia when administered after the insult.…”

“…Brain ischaemia, and particularly reperfusion after ischaemia, produces significant oxidative stress, which apparently contributes to cell death (Simonson et al 1993;Suzuki et al 1995). MAO inhibitors decrease free radical formation and thus could prevent cerebral damage (Matsui & Kumagae 1991;Simonson et al 1993;Suzuki et al 1995).…”

Biochemical, behavioral, physiologic, and neurodevelopmental changes in mice deficient in monoamine oxidase A or B

“…The second mechanism, contrary to the first, proposes that MAO B activity might be a risk factor in determining outcome following ischemia. The catabolism of bio-amines by monoamine oxidase is reported to increase during ischemia [18] with a resultant increased production in hydrogen peroxide (H 2 O 2 ) [76]. Inhibition of MAO B by L-deprenyl decreases the production of H 2 O 2 [59], and it has been hypothesized that this may attenuate neuronal damage by H 2 O 2 or the highly toxic hydroxyl radical which can be formed from H 2 O 2 by iron-mediated Fenton reactions.…”