MAO inhibitors, clorgyline and lazabemide, prevent hydroxyl radical generation caused by brain ischemia/reperfusion in mice.
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.
Suzuki
T
T
Department of Pharmacology, Nippon Roche Research Center, Kamakura, Japan.
Akaike
N
N
Ueno
K
K
Tanaka
Y
Y
Himori
N
N
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D003010:Clorgyline / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010848:Picolinic Acids / Q000494:pharmacology; D015424:Reperfusion
D008996:Monoamine Oxidase Inhibitors; D010848:Picolinic Acids; D015102:3,4-Dihydroxyphenylacetic Acid; D017665:Hydroxyl Radical; C059303:lazabemide; D003010:Clorgyline; D004298:Dopamine