HYDROXYL AND PEROXYL RADICAL TRAPPING BY THE MONOAMINE OXIDASE-B INHIBITORS DEPRENYL AND MDL-72,974A - IMPLICATIONS FOR PROTECTION OF BIOLOGICAL SUBSTRATES

We have examined in vitro radical trapping by the monoamine oxidase-B (MAO-B) inhibitor deprenyl and compared it to the specific MAO-B inhib itor MDL 72,974A. The capacity for the compounds to prevent . OH-media ted oxidation of biological substrates was examined by determining the ir ability to inhibit oxidation of 2-deoxyribose and phosphatidylcholi ne liposomes using the thiobarbituric acid reactive substances (TEARS) assay. MDL 72,974A gave a dose-dependent inhibition of 2-deoxyribose oxidation, while deprenyl generated a strong false positive TEARS reac tion with both the sugar and the liposomes. When lipid peroxidation wa s monitored by conjugated diene formation, deprenyl inhibited oxidatio n while MDL 72,974A was without effect suggesting that trapping of . O H was not responsible for activity. Deprenyl inhibited liposomal perox idation initiated with the water-soluble peroxyl radical generator 2,2 '-azobis (2-amidinopropane) (ABAP) with an IC50 of 78 mu M as compared to 4.2 mM for MDL 72,974A. A similar difference was observed using th e lipophilic peroxyl radical generator 2,2'-azobis (2,4-dimethylvalero nitrile) (AMVN). The data indicate that radical trapping by the MAO-B inhibitors provides differential protection against biological substra tes and may involve trapping of secondary peroxyl radicals rather than . OH. Copyright (C) 1997 by Elsevier Science Inc.