We know that healthy mitochondria, the energy factories of cells, rely on proper reduction and oxidation to keep us converting food to energy and staving off mitochondrial pathologies. Any number of compounds have been created to try and keep that going as we age. They determine whether cells live or die and they regulate inflammation.
One new compound, (AP39), targets delivery of very small amounts of hydrogen sulfide inside cells. Hydrogen sulfide. H2S. Sewer gas. It's that fart smell. The U.S. Department of Labor Occupational Safety&Health Administration (OSHA) says it is highly toxic and dangerous because it is flammable and explosive, along with causing rapid unconsciousness at higher levels. But it's natural, so that will make alternative medicine proponents happy; one man's herb is another man's fart smell.
At the right tiny dosage, the AP39 hydrogen sulfide protects mitochondria – the “powerhouse” of cells, which drive energy production in blood vessel cells. Preventing or reversing mitochondrial damage is a key strategy for treatments of a variety of conditions such as stroke, heart failure, diabetes and arthritis, dementia and aging.
Hydrogen sulfide is naturally produced in the body and could have significant implications for future therapies for a variety of diseases. Credit: University of Exeter.
Professor Matt Whiteman, of the University of Exeter Medical School, said, “When cells become stressed by disease, they draw in enzymes to generate minute quantities of hydrogen sulfide. This keeps the mitochondria ticking over and allows cells to live. If this doesn’t happen, the cells die and lose the ability to regulate survival and control inflammation. We have exploited this natural process by making a compound, called AP39, which slowly delivers very small amounts of this gas specifically to the mitochondria. Our results indicate that if stressed cells are treated with AP39, mitochondria are protected and cells stay alive.”
Dr. Mark Wood added, “Although hydrogen sulfide is well known as a pungent, foul-smelling gas in rotten eggs and flatulence, it is naturally produced in the body and could in fact be a healthcare hero with significant implications for future therapies for a variety of diseases.”
The research is being conducted in several models of disease. The results are pre-clinical but in models of cardiovascular disease,more than 80 percent of the powerhouse mitochondria cells survive under otherwise highly destructive conditions, if the AP39 is administered. They also found that the compound selectively prevented mitochondrial DNA in mitochondria. Once damaged, this DNA cannot be repaired, leaving individuals more vulnerable to disease symptoms.
Early indications in small-scale studies, presented at this year’s 3rd International Conference on Hydrogen Sulfide in Biology and Medicine in Kyoto, also show that in high blood pressure, AP39 reversed blood vessel stiffening and lowered blood pressure. It also dramatically improved chances of survival after a heart attack by slowing the heartbeat, improving its efficiency.
Dads, save a life, be a hydrogen sulfide donor. It will also make your kids giggle. Moms, stay classy instead.
Citation: Sophie Le Trionnaire, Alexis Perry, Bartosz Szczesny, Csaba Szabo, Paul G. Winyard, Jacqueline L. Whatmore, Mark E. Wood and Matthew Whiteman , 'The synthesis and functional evaluation of a mitochondria-targeted hydrogen sulfide donor, (10-oxo-10-(4-(3-thioxo-3H-1,2-dithiol-5-yl)phenoxy)decyl)triphenylphosphonium bromide (AP39)', Med. Chem. Commun., 2014,5, 728-736 DOI: 10.1039/C3MD00323J. Source: University of Exeter.
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