Pharmacological profile of a novel H(2)S-releasing aspirin.
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.
Sparatore
Anna
A
Istituto di Chimica Farmaceutica e Tossicologica "Pietro Pratesi", University of Milano, Italy. anna.sparatore@unimi.it
Perrino
Elena
E
Tazzari
Valerio
V
Giustarini
Daniela
D
Rossi
Ranieri
R
Rossoni
Giuseppe
G
Erdmann
Kati
K
Erdman
Kati
K
Schröder
Henning
H
Del Soldato
Piero
P
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
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