Release of glutathione from erythrocytes and other markers of oxidative stress in carbon monoxide poisoning.
Rats exposed to CO in a manner known to cause oxidative stress in brain exhibited a twofold increase in plasma levels of oxidized proteins, thiobarbituric acid-reactive substances (TBARS), oxidized glutathione (GSSG), and reduced glutathione (GSH). Changes were neither directly related to hypoxic stress from carboxyhemoglobin nor significantly influenced by circulating platelets or neutrophils. Treatment with the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester inhibited elevations in GSH and GSSG but not changes in oxidized proteins or TBARS, suggesting that two oxidative mechanisms may be operating in this model and that GSH and GSSG elevations involved nitric oxide-derived oxidants. Elevations of blood GSH and GSSG occurred at different anatomic sites, indicating that no single organ was the source of the increased peptides. Animals that underwent exchange transfusion with a hemoglobin-containing saline solution did not exhibit elevations in GSH and GSSG, suggesting that blood-borne cells released these peptides in response to oxidative stress. In in vitro studies, erythrocytes, but not platelets and leukocytes, responded to oxidative stress from peroxynitrite by releasing GSH, whereas no release was observed in response to nitric oxide or superoxide. Glucose, maltose, and cytochalasin B, agents that protect extracellular components of the hexose transport protein complex from oxidative stress, prevented GSH release. The data indicate that nitric oxide-derived oxidants are involved in CO-mediated oxidative stress within the vascular compartment and that elevations of several compounds may be useful for identifying exposures to CO likely to precipitate brain injury.
Thom
S R
SR
Institute for Environmental Medicine, University of Pennsylvania, Philadelphia 19104-6068, USA. SThom@mail.med.upenn.edu
Kang
M
M
Fisher
D
D
Ischiropoulos
H
H
D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D015415:Biomarkers; D001792:Blood Platelets / Q000378:metabolism; D002249:Carbon Monoxide Poisoning / Q000378:metabolism*; D003571:Cytochalasin B / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004906:Erythrocyte Count; D004910:Erythrocyte Membrane / Q000378:metabolism; D004912:Erythrocytes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D005978:Glutathione / Q000031:analogs & derivatives* / Q000097:blood; D019803:Glutathione Disulfide; D006601:Hexoses / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D015415:Biomarkers; D004791:Enzyme Inhibitors; D006601:Hexoses; D009566:Nitrates; D017392:Thiobarbituric Acid Reactive Substances; C039642:peroxynitric acid; D009569:Nitric Oxide; D003571:Cytochalasin B; C002385:linsidomine; D008981:Molsidomine; D005978:Glutathione; D019803:Glutathione Disulfide; D019331:NG-Nitroarginine Methyl Ester