Abstract
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.
Highlights
Carbon monoxide (CO) is a gaseous molecule known as the silent killer
Once formed, CO-hemoCD1 could not be reconverted to its deoxy form despite continuous N2 bubbling for 60 min, while CO-Hb returned to its deoxy form after N2 treatment (Supplementary Fig. S1)
CO content in hepatocytes exposed to the CO releaser followed by met-Hb was very similar to that of cells exposed to CORM401-E alone (Supplementary Fig. S12). These results indicate that CO initially accumulated in cells was subsequently transferred to Hb. These results suggest that Hb is capable of removing CO stored in cells, which was confirmed by the CO quantification assay using hemoCD1, and that this mechanism could occur in vivo, supporting a possible protective role of Hb against CO intoxication
Summary
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. 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. If the animals were first bled to reduce blood volume and transfused with red blood cells (RBC) saturated with CO, all dogs survived despite reaching CO-Hb levels of 60%16 These findings strongly indicate that inhalation of gaseous CO is highly toxic whereas CO-Hb is not, challenging the commonly accepted notion that the percentage of CO-Hb is the appropriate marker to establish the toxicity of CO inhalation. As we investigated and discuss in this paper, the headspace analysis by GC tends to underestimate the amount of CO, highlighting that a convenient and reliable method for measuring CO contained in organs/tissues is needed
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