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Hydrogen Sulfide Donors Protect Heart Cells

Chemical Biology: Compounds could react with thiol groups in the body to deliver the gas to tissue damaged after a heart attack

by Louisa Dalton
April 17, 2013

Heart Defenders
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Credit: Ming Xian
Thiols in biomolecules trigger new perthiol-based molecules to free hydrogen sulfide. Two of these compounds (shown) protect heart cells in mice, minutes following a heart attack.
Structures of two perthiol compounds.
Credit: Ming Xian
Thiols in biomolecules trigger new perthiol-based molecules to free hydrogen sulfide. Two of these compounds (shown) protect heart cells in mice, minutes following a heart attack.

A big breath of undiluted hydrogen sulfide can kill a person. Yet in recent years, researchers have discovered that the body regularly delivers small, precise doses of the gas to regulate blood pressure and protect cells from inflammation damage, including the damage following a heart attack.

Now chemists have synthesized a class of compounds that can selectively release hydrogen sulfide as possible treatments for damage to heart tissue (ACS Chem. Biol., DOI: 10.1021/cb400090d).

In the minutes following a heart attack, heart cells initially starved of oxygen get hit with even more damage when blood rushes back to the cells carrying inflammatory and oxidizing agents. Studies of rats and mice have shown that hydrogen sulfide protects the vulnerable heart cells from this further damage.

Physicians and researchers would like a method for delivering protective hydrogen sulfide to such vulnerable tissue. However, the gas itself is very difficult to control, says Ming Xian of Washington State University. It escapes from solution quickly, and researchers struggle to control how much reaches tissue. “Researchers need an agent that will release hydrogen sulfide in a controllable way,” he says.

Xian and his colleagues synthesized a group of penicillamine-based perthiol compounds that produce hydrogen sulfide when they react with two common biomolecules in the body, the amino acid cysteine or the peptide glutathione. The thiol groups in cysteine and glutathione trigger this release.

With David J. Lefer at Emory University, Xian found that the compounds protect heart cells in mice. When they injected one molecule into mice after a heart attack, the compound decreased heart tissue damage by 50% compared to animals not receiving the treatment.

Xian also is using the compounds to investigate how hydrogen sulfide protects cells.

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