Normally thought of as a poison, carbon monoxide (CO) is a “colorless, odorless, tasteless gas produced by burning gasoline, wood, propane, charcoal or other fuel.”
At high concentrations, CO can build up in the blood, displace oxygen in red blood cells, and cause tissue damage. Possible side effects include headaches, weakness, dizziness, nausea, vomiting, shortness of breath, confusion, blurry vision, and loss of consciousness.
However, a group of scientists from the Massachusetts Institute of Technology (MIT), Harvard Medical School, the University of Iowa, and other universities, published results of a study in the Science Translational Medicine journal on June 29, 2022 describing how a family of “gas-trapping materials (GEMs)” could be used to deliver CO to the gastrointestinal (GI) tract as a treatment for “diseases affecting the GI mucosa such as inflammatory bowel disease or radiation injury.”
One of the authors of the study, Leo E. Otterbein, Professor of Surgery at Beth Israel Deaconess Medical Center, stated that while the gas is toxic at high levels, carbon monoxide is becoming accepted as a potential therapeutic that can modulate inflammation, according to STAT news.
Coffee, gummy bears, and pop rocks
James D. Byrne, first author of the research article and an Assistant Professor of Oncology and Biomedical Engineering at University of Iowa Health Care who conducted his postdoctoral training at MIT, stated that his inspiration for developing GEMs was derived from whipping siphons at Starbucks.
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By building their own similar device pressurized to up to 200 psi (pounds per square inch), or about seven times the pressure of a car tire, they were able to trap CO gas inside small bubbles in a foam GEM.
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The selected medium has widespread applications due to its ability to be easily transported to different parts of the world.
Another viable delivery system was based on a gummy-bear-type system, with a gel used to trap CO. Byrnes described the system as an “ionic crosslinker sodium alginate within calcium chloride solution.”
Pop rocks also piqued the interest of the researchers, who delved into YouTube videos about how they are made and set out to create solid GEMs allowing for the controlled release of CO gas into the gut.
Giovanni Traverso, an Assistant Professor in the Department of Mechanical Engineering at MIT and another author of the study, stated, “One of the key goals from the outset was really to use source reagents or ingredients that are low cost, one for scalability and for a product to be viable not just efficacious.”
Carbon monoxide therapies
Perhaps the most obvious delivery method of therapeutic CO is through inhalation, but previous studies have revealed several challenges. One such challenge is “variability in patient ventilation, environmental safety concerns for patients and healthcare workers,” in addition to “the need for large amounts of compressed CO gas in cylinders that pose a health hazard due to the potential for cylinder leak or rapid depressurization.”
The formulations developed by the researchers were tested in “three small animal models associated with inflammation and oxidative stress–induced tissue injury: acetaminophen (APAP)–induced acute liver injury, experimental colitis, and radiation-induced proctitis.”
Acetaminophen is more commonly known as Tylenol, and experimental colitis resembles inflammatory diseases of the gut, such as ulcerative colitis and Crohn׳s disease.
Delivering CO through the gut is advantageous not only because of the “high diffusivity of CO across the epithelial barrier of the stomach and intestines,” the authors stated, but also on account of “local anti-inflammatory effects.”
When the foam is delivered through the rectum to the affected areas in the gut, less CO is needed to achieve the desired effect. Furthermore, since blood drains from the gut into the liver, administered CO can help to treat liver inflammation.
Other applications of CO administration include the treatment of infections and cancers, as well as diseases affecting the heart, lungs, and kidneys. Dr. Otterbein added that inhaled CO had been shown to help patients in respiratory distress, and is currently undergoing clinical trials in patients with lung disease.
He commented that there were “30 people walking around who were treated with carbon monoxide during their kidney transplants.”
Further research will involve producing a longer-acting formulation that can optimally be taken once daily. The foam can be delivered through either the mouth or rectum, and rectal formulations are generally well-tolerated.
However, safety and efficacy research is needed, especially of the use of the GEMs in humans.
