Summary of Overcomes Simultaneous Carbon Monoxide and Hydrogen Cyanide Poisoning:
A team of researchers led by Professor Hiroaki Kitagishi from Doshisha University in Japan have developed a novel heme-model compound called “hemoCD-Twins” which acts as an antidote for CO and HCN poisoning. The compound dissolves into two heme models in saline solution, with hemoCD-P capturing CO strongly and hemoCD-I scavenging CN- effectively. This has the potential to save the lives of people exposed to toxic gases in building fires, as there is currently no therapeutic approach available to overcome simultaneous CO and HCN poisoning. The team has demonstrated hemoCD-Twins to be a very effective and rapid antidote with a high degree of safety and storage stability. They hope that within 5-10 years, hemoCD-Twins can be incorporated in ambulances, emergency hospitals, and other facilities to save lives from gas poisoning. This work was funded by MEXT/JSPS KAKENHI, Translational Research Program from Japan Agency for Medical Research and Development, the Uehara Memorial Foundation, and Takahashi Industrial and Economic Research Foundation.

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A Novel Dual Antidote for Protection From Building Fire Gases

Buildings across the globe are prone to catching fires in unfortunate situations. Other than the flames, the burning materials generate highly toxic carbon monoxide (CO) and hydrogen cyanide (HCN) gases, which can be fatal upon ingestion. Once inhaled, these gases bind strongly to hemoglobin, cytochromes, and iron containing compounds known as “hemes,” and block normal aerobic respiration. It is believed that once an individual is exposed to these life-threatening toxins, it is impossible to effectively remove them from the body. In fact, at present, there is no therapeutic approach available to overcome simultaneous CO and HCN poisoning. This poses a significant challenge in saving the lives of people exposed to toxic gases in building fires.

In a recent breakthrough, a team of researchers led by Professor Hiroaki Kitagishi from the Faculty of Science and Engineering, Doshisha University, Japan has developed a synthetic heme-model compound termed “hemoCD-Twins,” that acts as an antidote for CO and HCN poisoning. Prof. Kitagishi and his collaborators—Dr. Qiyue Mao from Doshisha University, Dr. Xuansu Zhao from the Building Research Institute, Japan, Dr. Akiko Kiriyama from Doshisha Women’s College of Liberal Arts, Japan, and Dr. Roberto Motterlini from University Paris Est Creteil, France—have detailed the development of this novel antidote in their recent research article published today (February 20, 2023) in the Proceedings of the National Academy of Sciences (PNAS). In saline solution, hemoCD Twins dissolves into two heme models, of which hemoCD-P captures CO very strongly, and hemoCD-I effectively scavenges CN^–.

Highly toxic CO and HCN are simultaneously released during building fires. A new heme compound acts known as “hemoCD-Twins,” which is a mixture of heme-model compounds, rapidly expels CO and HCN from the body, acting as a powerful antidote. Credit: Prof. Hiroaki Kitagishi

Motivation Behind the Development of HemoCD-Twins

What was the motivation behind the development of this life-saving compound? Prof. Kitagishi recalls, “We have been studying synthetic heme-model compounds (hemoCDs) for over two decades. The series of hemoCDs, which comprises a mixture of synthetic organic compounds—porphyrin and cyclodextrins—has been our original heme-model system that realizes the biological functions of hemes using completely synthetic materials. One fine morning during the course of our research, I embarked on the idea that hemoCDs could be best used as antidotes against simultaneous poisoning by CO and HCN.”

The team has also demonstrated hemoCD-Twins to be a very effective and rapid antidote against CO and HCN simultaneous poisoning in mice models. They found that in mice, this compound resulted in an 85% survival rate and rapid recovery. Moreover, this dual antidote exhibited very low toxicity and rapid elimination via urinary excretion. In addition, hemoCD-Twins had an immediate antidotal effect, a high degree of safety, and storage stability.