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Research News: Success After COmbing for a Cure: HemoCD1 Against Carbon Monoxide Poisoning

July 29, 2021

Researchers synthesize hemoglobin-like molecules effective against carbon monoxide poisoning

Exposure to carbon monoxide (CO) beyond permissible limits can cause serious health emergencies, including permanent brain damage. Although conventional methods alleviate the worst of the symptoms, they still do not aid in effective elimination of CO accumulated in the tissues of the affected individuals. However, in a new breakthrough study, a group of researchers from Japan has now found success in eliminating this accumulated CO using a novel synthesized biomolecule, called hemoCD1.

More than 50,000 patient admissions in the emergency department, along with more than one trillion yen in associated costs, annually—such is the impact of CO poisoning in Japan, alone! With accidental fires and industrial effluents adding CO to the atmosphere in increasing concentrations, threatening human health, the world is in dire need of effective ways to tackle this menace.

Currently, patients presenting with CO poisoning in hospitals are treated with oxygen ventilation. However, previous research has already shown that CO has high affinity for circulating hemoglobin, forming carboxyhemoglobin, thus hitching a ride to all the tissues in the body, including the brain. It is also alarming to note that oxygen ventilation does not solve the problem of CO accumulation in the tissues, particularly in the brain. Such accumulated CO wreaks havoc, sometimes causing permanent brain damage.

Fortunately, Prof. Hiroaki Kitagishi from the Department of Molecular Chemistry and Biochemistry, Faculty of Science and Engineering, Doshisha University, Japan, has identified this serious problem and decided to form an international research team to find a solution. The other members of this research team include Ms. Qiyue Mao from Doshisha University, Dr. Akira T. Kawaguchi from Tokai University, Japan, and Drs. Roberto Motterlini and Roberta Foresti from French National Institute of Health and Medical Research, France.  The researchers had their eureka moment with the synthesis of a hemoglobin-like molecule called, hemoCD1! Their breakthrough findings have been published as a research article in Communications Biology.

Speaking about personal motivation for the study, Prof. Kitagishi says, “In our laboratory, we had been trying to construct artificial heme protein model compounds by organic synthesis. Eventually, we developed hemoCD1, a first and only-one hemoglobin/myoglobin model compound that binds oxygen and CO in water like hemoglobin. We had identified the very specific and high CO binding ability of hemoCD1. Around 10 years ago, we had discovered that hemoCD1 injected to the animal body captured CO and was smoothly excreted in the urine together with CO. This result was quite surprising, and we decided to use hemoCD1 as a selective CO removal agent in the mammalian body.”

Initially, the team of researchers systematically studied how CO inhaled from the external environment circulated in the blood and accumulated in the tissues. Then, the team applied conventional oxygen ventilation to study how this allows CO to be flushed out of the system. In tandem, they synthesized and characterized hemoCD1. Further, they used hemoCD1, along with oxygen ventilation, to observe the effects in animal models of CO poisoning.

What the researchers discovered was remarkable! Firstly, they established that oxygen ventilation does not effectively solve the problem of inhaled and accumulated CO in the tissues, particularly in the brain (Figure 1.). Secondly, they characterized the synthesized hemoCD1 to be similar to naturally occurring hemoglobin, but 100 times more effective in water, for capturing accumulated CO. Thirdly, compared to unbound hemoCD1, CO-bound hemoCD1 showed significantly different light absorbance, thus making it an ideal detector of CO levels (Figure 2.). Finally, when used in conjunction with oxygen ventilation, hemoCD1 was seen to effectively flush out accumulated CO, from the brain tissue too, as excreted urine (Figure 3.). Looks like the solution for tackling CO poisoning could have been found!

Excited about the success of their study, Prof. Kitagishi states, “HemoCD1 injected into the body acts as a sacrificial compound of hemoglobin and other heme proteins in the body. We believe that hemoCD1 will be used worldwide as the CO-removing agent in fire and toxic gas accidents.

The world can indeed hope for fast-tracked clinical applications of the lifesaving hemoCD1 against CO poisoning.

Figure 1. Carbon monoxide combines with hemoglobin in the blood, forming carboxyhemoglobin, thus entering circulation, and undergoing toxic accumulation in different tissues

Image courtesy: Hiroaki Kitagishi from Doshisha University

Figure 2. HemoCD1 is a synthesized molecule, similar to hemoglobin, which can be medically applied against carbon monoxide poisoning

Image courtesy: Hiroaki Kitagishi from Doshisha University

Figure 3. Injected hemoCD1, along with oxygen supply, circulates in the blood as oxy-hemoCD1, which on encountering carbon monoxide (CO) accumulated in tissues, is converted to CO-hemoCD1, which gets readily excreted in the urine

Image courtesy: Hiroaki Kitagishi from Doshisha University

Reference

Title of original paper: Sensitive quantification of carbon monoxide in vivo reveals a protective role of circulating hemoglobin in CO intoxication
Journal Communications Biology
DOI: 10.1038/s42003-021-01880-1    

Funding information

This study was funded by MEXT/JSPS KAKENHI through grant numbers, JP15H02569, JP17H02208, JP18KK0156, JP19K22260, JP19K22972, and JP20H02871; the MEXT-Supported Program for the Strategic Research Foundation at Private Universities (2015–2019); the Takeda Science Foundation; the NOVARTIS Foundation for the Promotion of Science, the Suntory Foundation for Life Sciences; and the JGC-S Scholarship Foundation, In addition, this study was financially supported by Otsuka Toshimi Scholarship Foundation; a Visiting Fellowship from IMRB/Inserm; and a grant from the Agence National de la Recherche, through ANR-19-CE18-003201SWEET-CO.

Profile

Dr. Hiroaki Kitagishi is a Professor in the Department of Molecular Chemistry and Biochemistry, Faculty of Science and Engineering, Doshisha University, Japan. He is a renowned expert in the fields of supramolecular, organic, bioinorganic, and biological chemistry, with over 15 years of professional experience. His salient findings, over the years, have been published in the form of more than 60 articles, academic reviews, etc. in reputed national and international journals.

Hiroaki Kitagishi

Professor, Faculty of Science and Engineering, Department of Molecular Chemistry and Biochemistry

Media contact

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Kyotanabe, Kyoto 610-0394, JAPAN
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