Inhibition of brain monoamine oxidase activity by the generation of hydroxyl radicals - Potential implications in relation to oxidative stress

Monoamine oxidase (MAO) is an enzyme involved in brain catabolism of monoam ine neurotransmitters whose oxidative deamination results in the production of hydrogen peroxide. It has been documented that hydrogen peroxide derive d from MAO activity represents a special source of oxidative stress in the brain. In this study we investigated the potential effects of the productio n of hydroxyl radicals ((OH)-O-.) on MAO-A and MAO-B activities using mitoc hondrial preparations obtained from rat brain. Ascorbic acid (100 muM) and Fe2+ (0.2, 0.4, 0.8, and 1.6 muM) were used to induce the production of (OH )-O-.. Results showed that the generation of (OH)-O-. significantly reduced both MAO-A (85-53%) and MAO-B (77-39%) activities, exhibiting a linear cor relation between both MAO-A and MAO-B activities and the amount of (OH)-O-. produced. The reported inhibition was found to be irreversible for both MA O-A and MAO-B. Assuming the proven contribution of MAO activity to brain ox idative stress, this inhibition appears to reduce this contribution when an overproduction of (OH)-O-. occurs. (C) 2001 Elsevier Science Inc. All righ ts reserved.