Protection against oxygen toxicity by intravenous injection of liposome-entrapped catalase and superoxide dismutase.
Protection against oxygen toxicity by intravenous injection of liposome-entrapped catalase and superoxide dismutase.
复制标题
通过静脉注射脂质体包埋的过氧化氢酶和超氧化物歧化酶来防止氧中毒。
DOI：
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发表时间：
1984
影响因子：
15.9
通讯作者：
B. Freeman
中科院分区：
文献类型：
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作者：
J. Turrens;J. Crapo;B. Freeman
在暴露前和暴露中静脉注射含有过氧化氢酶和超氧化物歧化酶的脂质体，使100%氧暴露大鼠的存活率从69.5 +/- 1.5 h提高到118.1 +/- 9.9 h（平均+/- SEM， P < 0.05）。100%氧气条件下存活时间的增加也与胸膜腔内液体的显著减少有关。注射含有过氧化氢酶和超氧化物歧化酶的脂质体的大鼠在100%氧气条件下提高了存活率，与注射盐水的对照组相比，尸检时肺湿重增加（2.9 +/- 0.2 g/肺比4.8 +/- 0.4 g/肺，平均+/- SE， P < 0.05）。静脉注射对照脂质体以及悬浮缓冲液中的过氧化氢酶和超氧化物歧化酶使平均胸腔积液量减少89%，对生存时间无显著影响。单次静脉注射含有过氧化氢酶或超氧化物歧化酶的脂质体2 h后，肺过氧化氢酶和超氧化物歧化酶活性分别提高3.1倍和1.7倍。空气暴露大鼠和100%氧暴露大鼠肺中超氧化物歧化酶活性也显著高于对照组，在对照组和氧暴露大鼠停止注射含酶脂质体24 h后，每12 h检测一次酶活性，持续36 h。在不含脂质体的情况下，静脉注射游离超氧化物歧化酶和过氧化氢酶，不增加相应的肺酶活性，影响胸腔积液量、肺湿重、或者延长暴露于100%氧气的大鼠的平均存活时间。肺和血浆中脂质体增强的125i标记过氧化氢酶的清除符合单室模型的一级动力学。当以脂质体增强过氧化氢酶活性清除率或放射性作为药代动力学研究参数时，增强肺过氧化氢酶的半衰期分别为1.9和2.6 h。脂质体包裹过氧化氢酶和超氧化物歧化酶活性在循环中的半衰期分别为2.5 h和4 h，而静脉注射过氧化氢酶和超氧化物歧化酶的循环半衰期分别为23 min和6 min。
Survival of rats exposed to 100% oxygen was increased from 69.5 +/- 1.5 to 118.1 +/- 9.9 h (mean +/- SEM, P less than 0.05) when liposomes containing catalase and superoxide dismutase were injected intravenously before and during exposure. The increased survival time in 100% oxygen was also associated with significantly less fluid in the pleural cavity. Rats injected with catalase- and superoxide dismutase-containing liposomes, which had increased survival in 100% oxygen, had increased lung wet weight upon autopsy compared with saline-injected controls (2.9 +/- 0.2 g/lung vs. 4.8 +/- 0.4 g/lung, mean +/- SE, P less than 0.05). Intravenous injection of control liposomes along with catalase and superoxide dismutase in the suspending buffer decreased the mean pleural effusion volume 89% and had no significant effect on survival time. Lung catalase and superoxide dismutase activities were increased 3.1- and 1.7-fold, respectively, 2 h after a single intravenous injection of liposomes containing catalase or superoxide dismutase. Superoxide dismutase activity was also significantly greater than controls in both air- and 100% oxygen-exposed rat lungs, when enzyme activity was assayed 24 h after cessation of injection of control and oxygen-exposed rats with enzyme-containing liposomes every 12 h for 36 h. Free superoxide dismutase and catalase injected intravenously in the absence of liposomes did not increase corresponding lung enzyme activities, affect pleural effusion volume, lung wet weight, or extend the mean survival time of rats exposed to 100% oxygen. The clearance of liposome-augmented 125I-labeled catalase from lung and plasma obeyed first order kinetics according to a one-compartment model. When clearance of liposome-augmented catalase activity or radioactivity were the parameters used for pharmacokinetic studies, the half-life of augmented lung catalase was 1.9 and 2.6 h, respectively. The half-life of liposome-entrapped catalase and superoxide dismutase activity in the circulation was 2.5 and 4 h, respectively, while intravenously injected catalase and superoxide dismutase had a circulation half-life of 23 and 6 min, respectively.