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A new antioxidant compound H-290/51 attenuates upregulation of constitutive isoform of heme oxygenase (HO-2) following trauma to the rat spinal cord.

Abstract
Influence of a new antioxidant compound H-290/51 on carbon monoxide (CO) production following spinal cord injury was examined using immunohistochemistry of the constitutive isoform of heme oxygenase-2 (HO-2) in a rat model. Subjection of rats to 5 h spinal cord injury by making an incision into the right dorsal horn of the T10-11 segments resulted in upregulation of HO-2 in the injured and adjacent T9 and T12 segments. At this time, disruption of the blood-spinal cord barrier (BSCB) permeability, edema formation and cell injury were more pronounced. Pretreatment with H-290/51 (50 mg/kg, p.o., 30 min before trauma) significantly attenuated the HO-2 immunoreactivity along with breakdown of the BSCB permeability, edema and cell injury. These results for the first time demonstrate that the antioxidant compound H-290/51 is capable of attenuating HO-2 expression and thereby influencing CO production. Furthermore, our observations indicate that oxidative stress is involved in CO production, as reflected by HO-2 expression, which is injurious to the cord and H-290/51 exerts powerful neuroprotective effects in spinal cord injury.
AuthorsH S Sharma, P Alm, P O Sjöquist, J Westman
JournalActa neurochirurgica. Supplement (Acta Neurochir Suppl) Vol. 76 Pg. 153-7 ( 2000) ISSN: 0065-1419 [Print] Austria
PMID11449996 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antioxidants
  • H290-51
  • Indoles
  • Carbon Monoxide
  • Heme Oxygenase (Decyclizing)
  • heme oxygenase-2
Topics
  • Animals
  • Antioxidants (pharmacology)
  • Carbon Monoxide (metabolism)
  • Edema (pathology, physiopathology)
  • Heme Oxygenase (Decyclizing) (antagonists & inhibitors, metabolism)
  • Indoles (pharmacology)
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord (enzymology, pathology, physiopathology)
  • Spinal Cord Ischemia (enzymology, pathology)
  • Up-Regulation (drug effects)

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