Sensitive quantification of carbon monoxide in vivo reveals a protective role of circulating hemoglobin in CO intoxication.
Sensitive quantification of carbon monoxide in vivo reveals a protective role of circulating hemoglobin in CO intoxication.
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DOI：
10.1038/s42003-021-01880-1
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发表时间：
2021-03-29
影响因子：
5.9
通讯作者：
Kitagishi H
中科院分区：
文献类型：
--
作者：
Mao Q;Kawaguchi AT;Mizobata S;Motterlini R;Foresti R;Kitagishi H
一氧化碳（CO）是一种气体分子，被称为无声杀手。人们普遍认为，血液碳氧血红蛋白（CO-Hb）的增加是定义CO中毒的最佳生物标志物，而组织中CO蓄积是死亡的最可能直接原因的事实却很少研究。除了气相色谱法外，没有其他可靠的方法来准确测定组织中的CO含量。在这里，我们报告的性质和用途的hemoCD 1，合成的超分子化合物组成的铁（II）卟啉和环糊精二聚体，作为一个简单的比色测定，以量化生物样品中的CO一个可访问的试剂。在正常条件下和暴露于CO后，从大鼠收集的各种器官组织中的测定进行了验证。CO处理后的血液和组织中的CO的动力学曲线表明，CO在组织中的积累被阻止循环Hb，揭示了在CO中毒的Hb的保护作用。此外，hemoCD 1在体内用作CO清除剂，表明其可作为O2通气的有效辅助剂，以消除器官（包括大脑）中积累的残留CO。这些发现开辟了新的治疗前景，以抵消与CO中毒相关的毒性。Mao等人报道了利用合成的超分子化合物hemoCD 1，通过简单的比色测定对一氧化碳进行高灵敏度定量。它可以揭示CO在包括大脑在内的器官中的分布，也可以作为CO清除剂清除器官中积累的残留CO。最后，作者表明循环血红蛋白在CO中毒中起保护作用。
Carbon monoxide (CO) is a gaseous molecule known as the silent killer. It is widely believed that an increase in blood carboxyhemoglobin (CO-Hb) is the best biomarker to define CO intoxication, while the fact that CO accumulation in tissues is the most likely direct cause of mortality is less investigated. There is no reliable method other than gas chromatography to accurately determine CO content in tissues. Here we report the properties and usage of hemoCD1, a synthetic supramolecular compound composed of an iron(II)porphyrin and a cyclodextrin dimer, as an accessible reagent for a simple colorimetric assay to quantify CO in biological samples. The assay was validated in various organ tissues collected from rats under normal conditions and after exposure to CO. The kinetic profile of CO in blood and tissues after CO treatment suggested that CO accumulation in tissues is prevented by circulating Hb, revealing a protective role of Hb in CO intoxication. Furthermore, hemoCD1 was used in vivo as a CO removal agent, showing that it acts as an effective adjuvant to O2 ventilation to eliminate residual CO accumulated in organs, including the brain. These findings open new therapeutic perspectives to counteract the toxicity associated with CO poisoning. Mao et al. report highly sensitive quantification of carbon monoxide with a simple colorimetric assay, exploiting a synthetic supramolecular compound, hemoCD1. It can reveal distribution of CO in organs including the brain and can also serve as a CO scavenger for residual CO accumulated in organs. Finally, the authors showed circulating hemoglobin plays a protective role in CO intoxication.
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