Dr. Mark Roth

Dr. Mark Roth

by James J. Galligan, Ph.D., Associate Chair,
Department of Pharmacology and Toxicology

You may have seen a recent news article about near death experiences on CNN.  Associated with this report was a story about the potential life saving effects of the supposedly toxic gas, hydrogen sulfide (H2S).  This is the gas that gives rotten eggs their characteristic smell and it was long thought that H2S was not only foul smelling but a deadly gas.  However, the CNN story goes on to discuss the work of Dr. Mark Roth who is studying the potentially protective and life saving effects of H2S.

Dr. Roth has shown in laboratory animals that H2S may protect cells and tissues against the toxic effects of ischemia (low oxygen supply to tissues and cells).  Ischemica occurs during a heart attack or stroke which block blood flow to the heart or brain respectively.  H2S may protect cells against the dangerous chemical reactions that occur in cells when their oxygen supply is reduced.

Hydrogen Sulfide 3d

Hydrogen Sulfide 3d

This is an interesting story as it highlights a potential function of one of the so-called gasotransmitters that are synthesized in cells of animals and humans.  These gasotransmitters include nitric oxide (NO) (not to be confused with nitrous oxide, “Laughing gas”), carbon monoxide (CO) (yes, the carbon monoxide that is the toxic component of automobile exhaust and the carbon monoxide detected by your in home carbon monoxide detector) and H2S.

NO is produced by the enzyme nitric oxide synthase and NO is produced in the nervous system, in blood vessels and by immune cells.  NO functions as a neurotransmitter in the brain and in the gastrointestinal tract.  NO also relaxes blood vessels to increase blood flow to tissues and it is released by immune cells as part of their defense mechanism against invading bacteria and viruses.

CO is produced by the enzyme heme oxygenase (HO) and CO is also a signaling molecule in the brain, the gastrointestinal tract and in blood vessels.  H2S is produced by three different enzymes: cystathionine-b-synthase (CBS), cystathionine-g-lyase (CGL), and 3-mercaptopyruvate sulfurtransferase (3MST).  H2S is also a signaling molecule in the brain, gut and blood vessels.  H2S is an antioxidant that reduces levels of the dangerous oxygen radicals that are paradoxically produced during ischemia and particularly during reperfusion of tissues when the blood supply is restored.  The oxygen radicals activate apoptosis (the programmed cell death mechanism) that is responsible for the permanent tissue injury that occurs during ischemia and subsequent reperfusion.  H2S may act as an endogenous anti-oxidant but, as Dr. Roth’s work has shown, exogenous H2S may also be a good anti-oxidant.

This story also points out the importance of basic research.  No one would have predicted that the foul smelling and toxic rotten egg gas would have the potential to be a life saving treatment.  However, basic laboratory science revealed the complexity of the H2S system and how its activation could protect tissues against ischemic injury.  The emerging H2S story is another example of how new drugs or other treatments for human disease can come from the most unlikely sources.

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