title: Toxic effect of hemoglobin on spinal cord neurons in culture.
abstract: The vulnerability of spinal cord neurons to hemoglobin was quantitatively assessed in primary cultures derived from fetal mice. Exposure to hemoglobin for 28 h in a serum-free medium resulted in concentration-dependent neuronal death, with an EC50 of 0.9 microM; glia were not injured. Neuronal death was decreased by the ferric iron chelator deferoxamine, the alpha-tocopherol analogue Trolox C, ascorbate, and exogenous catalase, but was potentiated by superoxide dismutase. Neuronal death was also increased by depletion of cellular glutathione with the gamma-glutamylcysteine synthetase inhibitor buthionine sulfoxamine; inhibition of endogenous catalase with 3-amino-1,2,4-triazole had no significant effect. These results suggest that hemoglobin is toxic to spinal neurons via an iron-dependent, oxidative mechanism involving a hydrogen peroxide intermediate, and support the hypothesis that hemoglobin release may contribute to neuronal loss after spinal cord trauma.
authors.affiliation: Division of Emergency Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
authors.forename: R F
authors.initials: RF
authors.lastname: Regan
authors.forename: Y
authors.initials: Y
authors.lastname: Guo
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002374:Catalase / Q000187:drug effects; D016923:Cell Death; D002478:Cells, Cultured; D004791:Enzyme Inhibitors; D005333:Fetus; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D006454:Hemoglobins / Q000494:pharmacology / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology; D013119:Spinal Cord Injuries / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D006454:Hemoglobins; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione