Regional H2O2 concentration in rat brain after hyperoxic convulsions.
O2 toxicity of the central nervous system (CNS) may be a result of enhanced generation of reactive O2 species such as superoxide and H2O2 at high PO2. In this study, we measured H2O2 production in six regions of the rat brain before and after convulsions induced by hyperbaric hyperoxia (HBO). H2O2 concentration was determined ex vivo using a method based on the H2O2-dependent decline in catalase activity in the presence of the irreversible inhibitor of compound I, 3-amino-1,2,4-triazole. Regional catalase activity in the brain ranged from 0.029 +/- 0.004 to 0.055 +/- 0.004 mumol O2.min-1.micrograms DNA-1 in cerebellum and medulla-pons, respectively. In the presence of aminotriazole, catalase activity declined after HBO-induced convulsions to 26-45% of normoxic values. The rates of inactivation of catalase were used to predict average steady-state values for H2O2 concentration in different brain structures. Estimated H2O2 concentrations during HBO varied from 31 to 51 pM in cerebellum and posterior subcortex and represented increases of 2.2-7.3 times normoxic values. These findings suggest that H2O2 is an important mediator of selective neuronal vulnerability to CNS O2 toxicity.
Piantadosi
C A
CA
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
Tatro
L G
LG
D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism*; D006931:Hyperbaric Oxygenation; D008297:Male; D008433:Mathematics; D009994:Osmolar Concentration; D011048:Polarography; D051381:Rats; D012640:Seizures / Q000209:etiology / Q000378:metabolism*; D014018:Tissue Distribution
D006861:Hydrogen Peroxide; D002374:Catalase; D000640:Amitrole