Abstract
The pharmacological profile of a new, safe, and effective hydrogen sulfide (H(2)S)-releasing derivative of aspirin (ACS14) is described. We report the synthesis of ACS14, and of its deacetylated metabolite (ACS21), the preliminary pharmacokinetics, and its in vivo metabolism, with the H(2)S plasma levels after intravenous administration in the rat. ACS14 maintains the thromboxane-suppressing activity of the parent compound, but seems to spare the gastric mucosa, by affecting redox imbalance through increased H(2)S/glutathione formation, heme oxygenase-1 promoter activity, and isoprostane suppression.
MeSH terms
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3T3 Cells
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Animals
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Aorta, Thoracic / enzymology
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Aorta, Thoracic / pathology
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Aspirin / administration & dosage
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Aspirin / analogs & derivatives*
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Aspirin / chemistry
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Aspirin / pharmacokinetics*
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Chromatography, High Pressure Liquid
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Disulfides / administration & dosage
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Disulfides / chemistry
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Disulfides / pharmacokinetics*
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Gastric Mucosa / pathology
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Glutathione / metabolism
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Heme Oxygenase-1 / genetics*
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Hydrogen Sulfide / blood*
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Isoprostanes / metabolism
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Male
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Mice
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Myocardium / enzymology*
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Myocardium / pathology
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Promoter Regions, Genetic / genetics
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Rats
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Rats, Wistar
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Thromboxanes / antagonists & inhibitors*
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Thromboxanes / blood
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Transcriptional Activation / drug effects
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Transfection
Substances
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2-acetyloxybenzoic acid 4-(3-thioxo-3H-1,2-dithiol-5-yl)phenyl ester
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Disulfides
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Isoprostanes
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Thromboxanes
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Heme Oxygenase-1
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Glutathione
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Aspirin
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Hydrogen Sulfide