[abstract] PREVENTION OF H2O2 GENERATION BY MONOAMINE OXIDASE PROTECTS AGAINST CNS O2 TOXICITY

Abstract

Toxicity to the central nervous system (CNS) by hyperbaric oxygen (HBO) presumably relates to increased production of reactive oxygen species and oxidation of key enzymes and lipids. The sites of generation of reactive oxygen species during HBO, however, have not been fully characterized in the brain. We investigated the relationship between protection from CNS O2 toxicity by a monoamine oxidase (MAO) inhibitor, pargyline, and regional generation of H2O2 in the brain in the presence of an irreversible inhibitor of catalase, aminotriazole (ATZ). After 30 min of HBO at 50 meters, pargyline significantly protected rats from CNS O2 toxicity while ATZ enhanced toxicity. The mortality of rats treated with HBO + ATZ, HBO alone, HBO + pargyline, and HBO + ATZ + pargyline was 9/12, 6/12, 0/12, and 0/12 respectively. In animals pretreated with ATZ, regional brain catalase activity decreased over time, but the enzyme activities in six brain regions were inactivated more rapidly by HBO. Since the inactivation of catalase by ATZ is H2O2 dependent, the decrease in enzyme activities is related quantitatively to the intracellular production of hydrogen peroxide during HBO. Pargyline (40 mg/kg, i.p.), administered to the rats 30 min before HBO inhibited brain MAO by more than 90% and prevented ATZ inhibition of catalase during HBO in all six brain regions (P< 0.05). These findings indicate that increased H2O2 by oxidative deamination of monoarnines during HBO is a major contributor to the pathogenesis of CNS O2 toxicity in rats.