AIR BLAST-INDUCED PULMONARY OXIDATIVE STRESS - INTERPLAY AMONG HEMOGLOBIN, ANTIOXIDANTS, AND LIPID-PEROXIDATION

Blast overpressure (BOP) is a phenomenon that describes the instantane ous rise in atmospheric pressure above ambient, resulting from the fir ing of large caliber weapons or from military or civilian explosions. Exposure to BOP results in injury to the gas-filled organs, such as th e lungs, which exhibit a contusion-type injury. We examined the effect s 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 l ung that was characterized by 1) a 3.5-fold decrease in total antioxid ant reserves, 2) a depletion of the major water-soluble antioxidants a scorbate and glutathione (GSH) by 50 and 75%, respectively, 3) a deple tion of lipid-soluble antioxidant vitamin E by 30%, 4) a 2.5-fold incr ease of fluorescent end products of lipid peroxidation, and 5) an incr eased methemoglobin (metHb) content at 60 min after exposure. To eluci date the role of released hemoglobin (Hb) in blast-induced oxidative s tress, we studied the interactions of oxyhemoglobin (oxyHb), metHb, an d the oxoferryl from of Hb free radical species with two physiological ly important reductants, ascorbate and GSH. We found that both ascorba te and GSH were able to convert oxyHb to metHb in a reaction that yiel ded the one-electron oxidation intermediates semidehydro-ascorbyl radi cal and glutathionyl radical, respectively. This reaction did not occu r under anaerobic conditions, suggesting that oxyHb-bound O-2 acted as the electron acceptor. OxyHb induced peroxidation of cis-parinaric ac id in the presence but not absence of ascorbate or GSH. Thus the proox idant action of water-soluble antioxidants via redox cycling of oxyHb and metHb may promote oxidative stress rather than prevent it.