The time course of hydroxyl radical formation following spinal cord injury: the possible role of the iron-catalyzed Haber-Weiss reaction.
This study explores whether the hydroxyl radical (*OH)-one of the most destructive reactive oxygen species-plays a role in secondary spinal cord injury (SCI). First, we measured the time course of *OH formation in rat spinal tissue after impact SCI by administering salicylate as a trapping agent into the intrathecal space of the cord and measuring the hydroxylation products of salicylate, 2,3- and 2,5-dihydroxybenzoic acid (2,3- and 2,5-DHBA) by HPLC. The 2,3-DHBA concentration was significantly higher in injured spinal tissue than in sham controls at 5 min, 1 and 3 h, but not at 5 h post-injury. Second, we generated *OH by administering H(2)O(2) and FeCl(2)/EDTA (Fenton's reagents) at the concentrations produced by SCI into the gray matter of the cord for 4 h and found that it induced significant cell loss at 24 h post-*OH exposure. Mn (III) tetrakis (4-benzoic acid) porphyrin(MnTBAP)-a broad spectrum reactive species scavenger-significantly reduced *OH-induced cell death. Finally, we generated superoxide and administered FeCl(3)/EDTA in the intrathecal space of the cord at the concentration produced by SCI and measured extracellular *OH formation in the gray matter of the cord by microdialysis sampling. We found that the levels of *OH significantly increased compared to the pre-administration level, indicating that *OH can be produced in vivo by the iron-catalyzed Haber-Weiss reaction. All together, we demonstrated that *OH is an endogenous secondary damaging agent following SCI and the metal-catalyzed Haber-Weiss reaction may contribute to early *OH formation after SCI.
Liu
Danxia
D
Department of Neurology, University of Texas Medical Branch, Galveston, 77555-0653, USA. dliu@utmb.edu
Liu
Jing
J
Sun
Dachuan
D
Wen
Jing
J
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D005296:Ferrous Compounds / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000378:metabolism*; D007501:Iron / Q000494:pharmacology / Q000502:physiology; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000378:metabolism*; D013997:Time Factors; D019820:Xanthine / Q000494:pharmacology
C045076:Fenton's reagent; D005296:Ferrous Compounds; D016166:Free Radical Scavengers; D008665:Metalloporphyrins; D016877:Oxidants; C097284:manganese(III)-tetrakis(4-benzoic acid)porphyrin; D019820:Xanthine; D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide; D007501:Iron; C029451:ferrous chloride