video: New discovery could lead to carbon monoxide (CO) poisoning antidote in humans. This material relates to a paper that appeared in the Dec. 7, 2016, issue of Science Translational Medicine, published by AAAS. The paper, by I. Azarov at Vascular Medicine Institute, University of Pittsburgh in Pittsburgh, Pa., and colleagues was titled, "Five-coordinate H64Q neuroglobin as a ligand-trap antidote for carbon monoxide poisoning." view more
Credit: University of Pittsburgh Medical Center
Researchers have designed a scavenger molecule that can trap and remove carbon monoxide (CO) from the bloodstream within minutes, protecting mice from this common "silent killer." The molecule may one day offer an injectable antidote to CO poisoning that could be rapidly administered by paramedics in the home or hospital, the scientists say. A toxic byproduct of burning fuel in cars, stoves, and other engines, CO is a leading cause of poisoning death worldwide, sending about 50,000 people to the emergency room each year in the U.S. alone. The colorless and odorless gas sticks to hemoglobin, which carries oxygen in red blood cells, preventing oxygen from reaching vital organs. In search of an antidotal therapy, which is currently unavailable, Ivan Azarov and colleagues turned to a hemoglobin-like protein found in the brain called neuroglobin. They tweaked the molecule to bind CO about 500 times more strongly than hemoglobin binds CO. While neuroglobin also attaches to oxygen, the engineered version bound to CO about 1,000 times more tightly than to oxygen, suggesting it selectively targets the dangerous compound. When infused into mice exposed to lethal levels of CO poisoning, the modified neuroglobin removed CO from red blood cells within minutes and rapidly cleared from the blood into urine, improving survival and restoring heart rate and blood pressure to normal. The scavenger molecule also proved more potent than pure oxygen therapy, a widely used treatment for CO poisoning. The authors emphasize that their CO antidote will require further testing for safety in large animal models.
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Journal
Science Translational Medicine