Sensitive quantification of carbon monoxide in vivo reveals a protective role of circulating hemoglobin in CO intoxication.

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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.

Fig. 8
A Normal conditions. Endogenous CO continuously produced in cells is stored in tissues, diffuses to Hb, and is exhaled. B Initial stage of CO inhalation. Inhaled CO forms CO-Hb in RBC and diffused to tissues. C A steady state during CO inhalation. CO accumulated in tissues gradually transfers to Hb in RBC based on the higher CO affinity of Hb versus intracellular CO targets (see Table 1 and text for details).

Mao, Q., Kawaguchi, A.T., Mizobata, S. et al. Sensitive quantification of carbon monoxide in vivo reveals a protective role of circulating hemoglobin in CO intoxication. Commun Biol 4, 425 (2021).

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