LeGrand T S, Aw T Y
Department of Molecular and Cellular Physiology, Louisiana State University Medical Center, Shreveport 71130, USA.
Am J Physiol. 1998 Feb;274(2):G376-84. doi: 10.1152/ajpgi.1998.274.2.G376.
We showed that hypoxia alters glutathione (GSH)-dependent detoxication and induces mucosal metabolic instability. To determine the impact of these changes and the role of reductant supply in intestinal lipid peroxide disposition, pair-fed (16 g/day) Sprague-Dawley rats were exposed to air (20.9% O2; n = 6) or 10% O2 (n = 6) for 10 days. Jejunal and ileal everted sacs were exposed to 75 microM peroxidized fish oil with or without 10 mM glucose or 1 mM GSH. Peroxide transport was determined as the abluminal recovery of thiobarbituric acid-reactive substances. Peroxide recovery in hypoxic intestine was twice that in normoxic intestine. Addition of GSH and glucose did not affect peroxide recovery, indicating reduced intracellular GSH-dependent metabolism and enhanced output by the hypoxic intestine. Glucose uptake by normoxic and hypoxic intestine is similar, whereas its utilization for detoxication is decreased in hypoxic cells. Determination of NADPH supply indicates that decreased glucose availability for NADPH production during hypoxia impairs GSH disulfide reduction, compromises hydroperoxide metabolism, and increases peroxide output from hypoxic intestine.
我们发现，缺氧会改变谷胱甘肽（GSH）依赖性解毒作用，并引发黏膜代谢不稳定。为了确定这些变化的影响以及还原剂供应在肠道脂质过氧化物处置中的作用，将成对喂养（每天16克）的斯普拉格-道利大鼠暴露于空气（20.9%氧气；n = 6）或10%氧气（n = 6）中10天。将空肠和回肠外翻囊暴露于75微摩尔过氧化鱼油中，添加或不添加10毫摩尔葡萄糖或1毫摩尔GSH。过氧化物转运通过硫代巴比妥酸反应性物质的腔外回收率来测定。缺氧肠道中的过氧化物回收率是常氧肠道中的两倍。添加GSH和葡萄糖并不影响过氧化物回收率，这表明缺氧肠道中细胞内GSH依赖性代谢降低，输出增强。常氧和缺氧肠道对葡萄糖的摄取相似，而缺氧细胞中其用于解毒的利用率降低。对NADPH供应的测定表明，缺氧期间用于NADPH生成的葡萄糖可用性降低会损害GSH二硫化物的还原，损害氢过氧化物代谢，并增加缺氧肠道的过氧化物输出。
