Toxic effect of hemoglobin on spinal cord neurons in culture

J Neurotrauma. 1998 Aug;15(8):645-53. doi: 10.1089/neu.1998.15.645.


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.

MeSH terms

  • Analysis of Variance
  • Animals
  • Catalase / drug effects
  • Cell Death
  • Cells, Cultured
  • Enzyme Inhibitors
  • Fetus
  • Glutathione / drug effects
  • Glutathione / metabolism
  • Hemoglobins / pharmacology
  • Hemoglobins / toxicity*
  • L-Lactate Dehydrogenase / metabolism
  • Mice
  • Mice, Inbred Strains
  • Neurons / drug effects*
  • Neurons / pathology
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology
  • Spinal Cord / drug effects*
  • Spinal Cord / pathology
  • Spinal Cord Injuries / chemically induced*
  • Spinal Cord Injuries / pathology
  • Spinal Cord Injuries / physiopathology
  • Superoxide Dismutase / metabolism


  • Enzyme Inhibitors
  • Hemoglobins
  • L-Lactate Dehydrogenase
  • Catalase
  • Superoxide Dismutase
  • Glutathione