Production of hydroxyl radical in the hippocampus after CO hypoxia or hypoxic hypoxia in the rat.
Carbon monoxide poisoning produces both immediate and delayed neuronal injury in selective regions of the brain that is not readily explained on the basis of tissue hypoxia. One possibility is that cellular injury during and after CO poisoning is related to the production of reactive oxygen species (ROS) by the brain. In this study, we hypothesized that the extent of ROS generation in the brain would be greater after CO than after hypoxic hypoxia due to intracellular uptake of CO. We assessed hydroxyl radical (OH.) production by comparing the nonenzymatic hydroxylation of salicylic acid to 2,3-dihydroxybenzoic acid (2,3-DHBA) in the hippocampus of the rat by microdialysis during either CO hypoxia or an exposure to hypoxic hypoxia that produced similar PO2 and cerebral blood flow (CBF) values in the region of microdialysis. We found neither control animals nor animals exposed to 30 min of hypoxic hypoxia at a mean tissue PO2 of 15 mmHg demonstrated significant increases in 2,3-DHBA production in the hippocampus over the 2-h the exposure. In contrast, CO exposed rats which also developed brain PO2 values in the range of 15 mmHg showed highly significant increases in 2,3-DHBA production. We conclude that cerebral oxidative stress in the hippocampus of the rat during CO hypoxia in vivo is not a direct effect of decreased tissue oxygen concentration.
Piantadosi
C A
CA
F.G. Hall Center for Hypobaric and Hyperbaric Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Zhang
J
J
Demchenko
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IT
D000818:Animals; D002249:Carbon Monoxide Poisoning / Q000378:metabolism* / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D006454:Hemoglobins / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D062385:Hydroxybenzoates / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism*; D006900:Hydroxylation; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D018384:Oxidative Stress; D010101:Oxygen Consumption; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012459:Salicylates / Q000378:metabolism; D020156:Salicylic Acid
D006454:Hemoglobins; D062385:Hydroxybenzoates; D017382:Reactive Oxygen Species; D012459:Salicylates; D017665:Hydroxyl Radical; C009135:2,3-dihydroxybenzoic acid; D020156:Salicylic Acid