Existence of a threshold for hydroxyl radical generation independent of hypoxia in rat striatum during carbon monoxide poisoning
Existence of a threshold for hydroxyl radical generation independent of hypoxia in rat striatum during carbon monoxide poisoning
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DOI：
10.1007/s00204-010-0637-2
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发表时间：
2011-09-01
影响因子：
6.1
通讯作者：
Mukai, Toshiji
中科院分区：
文献类型：
--
作者：
Hara, Shuichi;Mizukami, Hajime;Mukai, Toshiji
我们研究了缺氧在一氧化碳（CO）诱导的纹状体羟自由基（（OH）-O-aEuro cent）产生中的作用，羟自由基可能导致CO中毒引起的脑损伤。自由活动的大鼠暴露于1,000和3,000 ppm的CO或8和5%O-2 40分钟造成浓度依赖性缺氧条件下的碳氧血红蛋白（COHb），脱氧血红蛋白，氧合血红蛋白，和O-2含量在动脉血。低氧条件下，3,000 ppm的CO和5%的O-2之间似乎是相当的，虽然pH值和部分O-2压力（PO 2）的变化是复杂的和浓度无关的。在纹状体中，CO和低O-2分别以浓度依赖性和浓度非依赖性方式降低组织PO 2水平，但暴露结束时的水平在所有组中相当。这也是纹状体血流量增加的情况。虽然细胞外谷氨酸（兴奋性），牛磺酸（抑制性）和丙氨酸（非神经递质）的增加，在纹状体对CO和低O-2的反应是复杂的，3,000 ppm的CO和5%的O-2具有可比的效果。因此，3，000 ppm CO和5%O-2似乎诱导了相当的缺氧条件。然而，前者比后者更强烈地刺激纹状体中（OH）-O-α-受体的产生。此外，与引起（OH）-O-a浓度依赖性增加的低O-2相反，1，000 ppm CO没有影响。研究结果表明，纹状体（OH）-O-α-Euro cent的产生由于CO中毒可能是独立的缺氧本身，并可能存在一个阈值。
We examined the role of hypoxia in the carbon monoxide (CO)-induced generation of the hydroxyl radical ((OH)-O-aEuro cent) in the striatum, which could contribute to brain damage due to CO poisoning. Exposure of free-moving rats to 1,000 and 3,000 ppm CO or 8 and 5% O-2 for 40 min caused concentration-dependent hypoxic conditions in terms of carboxyhemoglobin (COHb), deoxyhemoglobin, oxyhemoglobin, and O-2 contents in arterial blood. The hypoxic conditions seemed comparable between 3,000 ppm CO and 5% O-2, although alterations of pH and partial O-2 pressure (PO2) were complex and concentration independent. In the striatum, CO and low O-2 decreased tissue PO2 levels in a concentration-dependent and concentration-independent manner, respectively, but levels at the end of exposure were comparable among all groups. This was also the case for the increase in striatal blood flow. Although the increases in extracellular glutamate (excitatory), taurine (inhibitory), and alanine (non-neurotransmitter), in the striatum in response to CO and low O-2 were complex, 3,000 ppm CO and 5% O-2 had comparable effects. Thus, 3,000 ppm CO and 5% O-2 seemed to induce comparable hypoxic conditions. Nevertheless, the former more strongly stimulated (OH)-O-aEuro cent generation in the striatum than the latter. In addition, in contrast to low O-2 which caused a concentration-dependent increase in (OH)-O-aEuro cent, 1,000 ppm CO had no effect. The findings suggest that striatal (OH)-O-aEuro cent generation due to CO poisoning may be independent of hypoxia per se and that a threshold might exist.