It may smell of flatulence and have a reputation for being highly toxic, but when used in the right dosage, hydrogen sulfide may offer health benefits in a range of diseases such as diabetes, heart attack and dementia.
A new compound (AP39), developed at the University of Exeter, could hold the key to future therapies, by targeting delivery of very small amounts of the substance to the right (or key) places inside cells.
Scientists in Exeter have already found that the compound 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 ageing, researchers said. Mitochondria determine whether cells live or die and they regulate inflammation. In the clinic, dysfunctional mitochondria are strongly linked to disease severity.
"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," Professor Matt Whiteman of Exeter Medical School, said.
"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," said Whiteman.
"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," Dr Mark Wood of Biosciences, at the University of Exeter, added.
The research is being conducted in several models of disease, and pre-clinical results are promising. For example, in models of cardiovascular disease, research shows that more than 80% of the powerhouse mitochondria cells survive under otherwise highly destructive conditions, if the AP39 is administered. Whiteman and Wood are now working towards advancing the research to a stage where it can be tested in humans.
The study was published in the journal Medicinal Chemistry Communications. A follow-up study, published in The Nitric Oxide Journal with collaborators from the University of Texas Medical Branch, also found that the compound selectively prevented mitochondrial DNA in mitochondria.