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Hydrogen sulfide mediates the vasoactivity of garlic
Gloria A. Benavides*,,
Giuseppe L. Squadrito*,,
Robert W. Mills*,
Hetal D. Patel,
T. Scott Isbell,,
Rakesh P. Patel,,
Victor M. Darley-Usmar,,
Jeannette E. Doeller*,, and
David W. Kraus*,,,¶
Departments of *Environmental Health Sciences, Biology, and Pathology and Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL 35294
Edited by Solomon H. Snyder, Johns Hopkins University School of Medicine, Baltimore, MD, and approved September 12, 2007
Received for publication June 18, 2007.
Abstract:
The consumption of garlic is inversely correlated with the progressionof cardiovascular disease, although the responsible mechanismsremain unclear. Here we show that human RBCs convert garlic-derivedorganic polysulfides into hydrogen sulfide (H2S), an endogenouscardioprotective vascular cell signaling molecule. This H2Sproduction, measured in real time by a novel polarographic H2Ssensor, is supported by glucose-maintained cytosolic glutathionelevels and is to a large extent reliant on reduced thiols inor on the RBC membrane. H2S production from organic polysulfidesis facilitated by allyl substituents and by increasing numbersof tethering sulfur atoms. Allyl-substituted polysulfides undergonucleophilic substitution at the carbon of the allyl substituent,thereby forming a hydropolysulfide (RSnH), a key intermediateduring the formation of H2S. Organic polysulfides (R-Sn-R';n > 2) also undergo nucleophilic substitution at a sulfuratom, yielding RSnH and H2S. Intact aorta rings, under physiologicallyrelevant oxygen levels, also metabolize garlic-derived organicpolysulfides to liberate H2S. The vasoactivity of garlic compoundsis synchronous with H2S production, and their potency to mediaterelaxation increases with H2S yield, strongly supporting ourhypothesis that H2S mediates the vasoactivity of garlic. Ourresults also suggest that the capacity to produce H2S can beused to standardize garlic dietary supplements.
¶To whom correspondence should be addressed at: Departments of Biology and Environmental Health Sciences, University of Alabama at Birmingham, Ryals 530B, 1665 University Boulevard, Birmingham, AL 35294-0022. E-mail: dwkraus{at}uab.edu
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,
Giuseppe L. Squadrito*,
,
T. Scott Isbell
,
Rakesh P. Patel
carbon of the allyl substituent, thereby forming a hydropolysulfide (RSnH), a key intermediate during the formation of H2S. Organic polysulfides (R-Sn-R'; n > 2) also undergo nucleophilic substitution at a sulfur atom, yielding RSnH and H2S. Intact aorta rings, under physiologically relevant oxygen levels, also metabolize garlic-derived organic polysulfides to liberate H2S. The vasoactivity of garlic compounds is synchronous with H2S production, and their potency to mediate relaxation increases with H2S yield, strongly supporting our hypothesis that H2S mediates the vasoactivity of garlic. Our results also suggest that the capacity to produce H2S can be used to standardize garlic dietary supplements. 
