Prevention of H2O2 generation by monoamine oxidase protects against CNS O2 toxicity.
Toxicity to the central nervous system (CNS) by hyperbaric oxygen (HBO) presumably relates to increased production of reactive oxygen species. The sites of generation of reactive oxygen species during HBO, however, have not been fully characterized in the brain. We investigated the relationship between regional generation of hydrogen peroxide (H2O2) in the brain in the presence of an irreversible inhibitor of catalase, aminotriazole (ATZ), and protection from CNS O2 toxicity by a monoamine oxidase (MAO) inhibitor, pargyline. At 6 ATA of oxygen, pargyline significantly protected rats from CNS O2 toxicity whereas ATZ enhanced O2 toxicity. In animals pretreated with ATZ, HBO inactivated 21-40% more catalase than air exposure in the six brain regions studied. Because ATZ-mediated inactivation of catalase was H2O2 dependent, the decrease in catalase activity during hyperoxia was proportional to the intracellular production of H2O2. Pargyline, administered 30 min before HBO, inhibited MAO by greater than 90%, prevented ATZ inhibition of catalase activity during HBO, and reversed the augmentation of CNS O2 toxicity by ATZ. These findings indicate that H2O2 generated by MAO during hyperoxia is important to the pathogenesis of CNS O2 toxicity in rats.
Zhang
J
J
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
Piantadosi
C A
CA
D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects; D002374:Catalase / Q000037:antagonists & inhibitors; D002395:Catecholamines / Q000378:metabolism; D002493:Central Nervous System Diseases / Q000139:chemically induced / Q000517:prevention & control*; D004247:DNA / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism*; D006931:Hyperbaric Oxygenation / Q000009:adverse effects; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000633:toxicity*; D010293:Pargyline / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D002395:Catecholamines; D008996:Monoamine Oxidase Inhibitors; D004247:DNA; D010293:Pargyline; D006861:Hydrogen Peroxide; D002374:Catalase; D008995:Monoamine Oxidase; D010100:Oxygen; D000640:Amitrole