title: Pharmacological profile of a novel H(2)S-releasing aspirin.
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.
authors.affiliation: Istituto di Chimica Farmaceutica e Tossicologica "Pietro Pratesi", University of Milano, Italy. anna.sparatore@unimi.it
authors.forename: Anna
authors.initials: A
authors.lastname: Sparatore
authors.forename: Elena
authors.initials: E
authors.lastname: Perrino
authors.forename: Valerio
authors.initials: V
authors.lastname: Tazzari
authors.forename: Daniela
authors.initials: D
authors.lastname: Giustarini
authors.forename: Ranieri
authors.initials: R
authors.lastname: Rossi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Rossoni
authors.forename: Kati
authors.initials: K
authors.lastname: Erdmann
authors.forename: Kati
authors.initials: K
authors.lastname: Erdman
authors.forename: Henning
authors.initials: H
authors.lastname: Schröder
authors.forename: Piero
authors.initials: P
authors.lastname: Del Soldato
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001013:Aorta, Thoracic / Q000201:enzymology / Q000473:pathology; D001241:Aspirin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004220:Disulfides / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D005753:Gastric Mucosa / Q000473:pathology; D005978:Glutathione / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006862:Hydrogen Sulfide / Q000097:blood*; D028421:Isoprostanes / Q000378:metabolism; D008297:Male; D051379:Mice; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D013931:Thromboxanes / Q000037:antagonists & inhibitors* / Q000097:blood; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection
chemical_list: C577776:2-acetyloxybenzoic acid 4-(3-thioxo-3H-1,2-dithiol-5-yl)phenyl ester; D004220:Disulfides; D028421:Isoprostanes; D013931:Thromboxanes; D051547:Heme Oxygenase-1; D005978:Glutathione; D001241:Aspirin; D006862:Hydrogen Sulfide