Gorbunov N V, Elsayed N M, Kisin E R, Kozlov A V, Kagan V E
Department of Respiratory Research, Walter Reed Army Institute of Research, Washington, District of Columbia 20307, USA.
Am J Physiol. 1997 Feb;272(2 Pt 1):L320-34. doi: 10.1152/ajplung.1997.272.2.L320.
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.
爆炸超压（BOP）是一种描述大气压力瞬间高于环境压力的现象，它由大口径武器发射或军事或民用爆炸引起。暴露于爆炸超压会导致肺部等充气器官受伤，表现为挫伤型损伤。我们研究了大鼠在暴露于低水平爆炸超压（62±3 kPa）后5分钟和60分钟时爆炸超压的影响。结果发现，这种暴露会导致肺部产生氧化应激，其特征为：1）总抗氧化储备减少3.5倍；2）主要水溶性抗氧化剂抗坏血酸和谷胱甘肽（GSH）分别消耗50%和75%；3）脂溶性抗氧化剂维生素E消耗30%；4）脂质过氧化荧光终产物增加2.5倍；5）暴露后60分钟时高铁血红蛋白（metHb）含量增加。为了阐明释放的血红蛋白（Hb）在爆炸诱导的氧化应激中的作用，我们研究了氧合血红蛋白（oxyHb）、高铁血红蛋白（metHb）以及Hb自由基物种的高铁血红素与两种生理上重要的还原剂抗坏血酸和谷胱甘肽之间的相互作用。我们发现，抗坏血酸和谷胱甘肽都能够在一个反应中将氧合血红蛋白转化为高铁血红蛋白，该反应分别产生单电子氧化中间体半脱氢抗坏血酸自由基和谷胱甘肽自由基。此反应在厌氧条件下不发生，这表明与氧合血红蛋白结合的O2充当了电子受体。在有抗坏血酸或谷胱甘肽存在但无其不存在的情况下，氧合血红蛋白会诱导顺式紫黄质酸的过氧化。因此，水溶性抗氧化剂通过氧合血红蛋白和高铁血红蛋白的氧化还原循环产生的促氧化作用可能会促进氧化应激而非预防它。
