Air blast-induced pulmonary oxidative stress: interplay among hemoglobin, antioxidants, and lipid peroxidation.
Blast overpressure (BOP) is a phenomenon that describes the instantaneous rise in atmospheric pressure above ambient, resulting from the firing of large caliber weapons or from military or civilian explosions. Exposure to BOP results in injury to the gas-filled organs, such as the lungs, which exhibit a contusion-type injury. We examined the effects of BOP in rats at 5 and 60 min after exposure to a low-level BOP (62 +/- 3 kPa). The exposure was found to cause oxidative stress in the lung that was characterized by 1) a 3.5-fold decrease in total antioxidant reserves, 2) a depletion of the major water-soluble antioxidants ascorbate and glutathione (GSH) by 50 and 75%, respectively, 3) a depletion of lipid-soluble antioxidant vitamin E by 30%, 4) a 2.5-fold increase of fluorescent end products of lipid peroxidation, and 5) an increased methemoglobin (metHb) content at 60 min after exposure. To elucidate the role of released hemoglobin (Hb) in blast-induced oxidative stress, we studied the interactions of oxyhemoglobin (oxyHb), metHb, and the oxoferryl from of Hb free radical species with two physiologically important reductants, ascorbate and GSH. We found that both ascorbate and GSH were able to convert oxyHb to metHb in a reaction that yielded the one-electron oxidation intermediates semidehydroascorbyl radical and glutathionyl radical, respectively. This reaction did not occur under anaerobic conditions, suggesting that oxyHb-bound O2 acted as the electron acceptor. OxyHb induced peroxidation of cis-parinaric acid in the presence but not absence of ascorbate or GSH. Thus the prooxidant action of water-soluble antioxidants via redox cycling of oxyHb and metHb may promote oxidative stress rather than prevent it.
Gorbunov
N V
NV
Department of Respiratory Research, Walter Reed Army Institute of Research, Washington, District of Columbia 20307, USA.
Elsayed
N M
NM
Kisin
E R
ER
Kozlov
A V
AV
Kagan
V E
VE
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001205:Ascorbic Acid / Q000378:metabolism; D001711:Biotransformation; D001753:Blast Injuries / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D005978:Glutathione / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism*; D008054:Lipid Peroxides / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008297:Male; D008706:Methemoglobin / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010108:Oxyhemoglobins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013438:Sulfhydryl Compounds / Q000378:metabolism; D014810:Vitamin E / Q000378:metabolism
D000975:Antioxidants; D006454:Hemoglobins; D008054:Lipid Peroxides; D010108:Oxyhemoglobins; D013438:Sulfhydryl Compounds; D014810:Vitamin E; D008706:Methemoglobin; D005978:Glutathione; D001205:Ascorbic Acid