MAO Inhibitors, Clorgyline and Lazabemide, Prevent Hydroxyl Radical Generation Caused by Brain Ischemia/Reperf usion in Mice

Abstract

The effects of clorgyline, the MAO-A inhibitor, and lazabemide, the MAO-B inhibitor, on the levels of the hydroxyl radicals appearing in the cerebral ventricles of mice during brain ischemia/reperfusion were examined by using a salicylate trapping method. The amount of hydroxyl radicals formed peaked at 20 min after reperfusion (approximately 150% vs. basal level). The dopamine level markedly increased shortly after the initiation of an ischemic insult and thereafter waned. By contrast, the concentration of 3,4-dihydroxyphenylacetic acid (DOPAC) level decreased during a 40-min period of ischemia, gradually returning to the preischemic basal level upon reperfusion. The ischemia reperfusion-induced hydroxyl radical generation was attenuated by 3 mg/kg of clorgyline and lazabemide. Furthermore, mice pretreated with these MAO inhibitors showed decreased DOPAC levels in comparison with those of their respective vehicle-treated control groups; recovery of the reduced DOPAC level was also delayed. In conclusion, it is likely that both type A and type B MAOs participate in the generation of hydroxyl radicals during brain ischemia/reperfusion. This finding suggests the possible use of MAO inhibitors as neuroprotective agents for treating ischemic injury.

Antioxidant properties and protective effects of a standardized extract of Hypericum perforatum on hydrogen peroxide-induced oxidative damage in PC12 cells

“…The antioxidant properties of traditional antidepressant drugs have been evaluated. The MAO-A inhibitors clorgyline and deprenyl, potently inhibit hydroxyl radical generation (Suzuki et al, 1995). Likewise, bifemelane, a compound used in the treatment of emotional disturbances associated with aging and cerebrovascular disease, prevents hydroxyl radical formation and inhibits superoxide production (Yoshida et al, 1994).…”

Catecholamine Metabolism: A Contemporary View with Implications for Physiology and Medicine

“…The usually suggested mechanisms involve MAO-induced formation of hydroxyl radicals and autooxidation of the large amounts of catecholamines released from stores during the initial insult (Jewett et al, 1989;Damsma et al, 1990;Simonson et al, 1993;Suzuki et al, 1995;Kunduzova et al, 2002;Bianchi et al, 2003). Although rarely considered, MAO-catalyzed production of toxic catecholaldehydes during reoxygenation could also contribute to the injury.…”

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.…”

“…Whether the therapeutic effects are only palliative in nature or due to true neuroprotection is controversial. The neuroprotective influence of l-deprenyl is supported by data from cell culture and numerous in vivo models, including cerebral ischaemia (Salo & Tatton, 1992, Lahtinen et al 1997.The exact neuroprotective mechanism of l-deprenyl is not known, but it might be related to diminished oxidative stress (Matsui & Kumagae 1991;Wu et al 1993;Suzuki et al 1995). One of the early responses to cerebral ischaemia is a massive release of neurotransmitters, including the catecholamines dopamine and noradrenaline (Globus et al 1988).…”

“…The exact neuroprotective mechanism of l-deprenyl is not known, but it might be related to diminished oxidative stress (Matsui & Kumagae 1991;Wu et al 1993;Suzuki et al 1995). One of the early responses to cerebral ischaemia is a massive release of neurotransmitters, including the catecholamines dopamine and noradrenaline (Globus et al 1988).…”