Hyperoxia increases H2O2 production by brain in vivo.
Hyperoxia increases H2O2 production by brain in vivo.
复制标题
DOI：
10.1152/jappl.1987.63.1.353
复制
发表时间：
1987-07
影响因子：
3.3
通讯作者：
T. Yusa;J. Beckman;J. Crapo;B. Freeman
中科院分区：
文献类型：
--
作者：
T. Yusa;J. Beckman;J. Crapo;B. Freeman
体内注射3-氨基-1，2，4-三氮唑后，高氧和高压氧增加了非麻醉大鼠脑内过氧化氢(H_2O_2)的产生速率，这是通过H_2O_2介导的内源性过氧化氢酶活性失活来衡量的。3-氨基-1，2，4-三氮唑注射后30、60和120分钟，呼吸空气(0.2 ATA O2)的大鼠脑内过氧化氢酶活性分别下降到对照组的75%、61%和40%。暴露于0.6 ATA O2(3 ATA空气)、1.0 ATA O2(常压100%O2)和3.0 ATA O2(3 ATA 100%O2)的大鼠过氧化氢酶失活速率与0.2 ATA O2(室内空气)相比呈线性增加。用乙醇(4g/kg)预处理大鼠可防止过氧化氢酶失活，乙醇是活性过氧化氢酶-过氧化氢中间体的竞争性底物，化合物I。这证实了3-氨基-1，2，4-三氮唑使过氧化氢酶失活是由于形成过氧化氢酶-过氧化氢中间体，化合物I。过氧化氢酶失活的线性速率允许根据公式计算脑内过氧化氢酶的平均稳态过氧化氢浓度：[过氧化氢]=6.6 pm+5.6 ATA-1 X pm X[O2]，其中[O2]是大鼠呼吸的ATA中的氧浓度。因此，暴露在室内空气中的大鼠大脑中的过氧化氢浓度计算出约为7.7 PM，当氧分压增加到100%O2时增加60%，在3ATA 100%O2时增加300%，在那里中枢神经系统毒性症状最先显现。这些研究支持这样一种观点，即过氧化氢是O2引起的中枢神经系统损伤的重要介质。
Hyperoxia and hyperbaric hyperoxia increased the rate of cerebral hydrogen peroxide (H2O2) production in unanesthetized rats in vivo, as measured by the H2O2-mediated inactivation of endogenous catalase activity following injection of 3-amino-1,2,4-triazole. Brain catalase activity in rats breathing air (0.2 ATA O2) decreased to 75, 61, and 40% of controls due to endogenous H2O2 production at 30, 60, and 120 min, respectively, after intraperitoneal injection of 3-amino-1,2,4-triazole. The rate of catalase inactivation increased linearly in rats exposed to 0.6 ATA O2 (3 ATA air), 1.0 ATA O2 (normobaric 100% O2) and 3.0 ATA O2 (3 ATA 100% O2) compared with 0.2 ATA O2 (room air). Catalase inactivation was prevented by pretreatment of rats with ethanol (4 g/kg), a competitive substrate for the reactive catalase-H2O2 intermediate, compound I. This confirmed that catalase inactivation by 3-amino-1,2,4-triazole was due to formation of the catalase-H2O2 intermediate, compound I. The linear rate of catalase inactivation allows estimates of the average steady-state H2O2 concentration within brain peroxisomes to be calculated from the formula: [H2O2] = 6.6 pM + 5.6 ATA-1 X pM X [O2], where [O2] is the concentration of oxygen in ATA that the rats are breathing. Thus the H2O2 concentration in brains of rats exposed to room air is calculated to be about 7.7 pM, rises 60% when O2 tension is increased to 100% O2, and increases 300% at 3 ATA 100% O2, where symptoms of central nervous system toxicity first become apparent. These studies support the concept that H2O2 is an important mediator of O2-induced injury to the central nervous system.