title: H(2)S-releasing aspirin protects against aspirin-induced gastric injury via reducing oxidative stress.
abstract: The aim of this study was to examine the effect of ACS14, a hydrogen sulfide (H(2)S)-releasing derivative of aspirin (Asp), on Asp-induced gastric injury. Gastric hemorrhagic lesions were induced by intragastric administration of Asp (200 mg/kg, suspended in 0.5% carboxymethyl cellulose solutions) in a volume of 1 ml/100 g body weight. ACS14 (1, 5 or 10 mg/kg) was given 30 min before the Asp administration. The total area of gastric erosions, H(2)S concentration and oxidative stress in gastric tissues were measured three hours after administration of Asp. Treatment with Asp (200 mg/kg), but not ACS14 (430 mg/kg, at equimolar doses to 200 mg/kg Asp), for 3 h significantly increased gastric mucosal injury. The damage caused by Asp was reversed by ACS14 at 1-10 mg/kg in a concentration-dependent manner. ACS14 abrogated Asp-induced upregulation of COX-2 expression, but had no effect on the reduced PGE(2) level. ACS14 reversed the decreased H(2)S concentrations and blood flow in the gastric tissue in Asp-treated rats. Moreover, ACS14 attenuated Asp-suppressed superoxide dismutase-1 (SOD-1) expression and GSH activity, suggesting that ACS14 may stimulate antioxidants in the gastric tissue. ACS14 also obviously inhibited Asp-induced upregulation of protein expression of oxidases including XOD, p47(phox) and p67(phox). In conclusion, ACS14 protects Asp induced gastric mucosal injury by inhibiting oxidative stress in the gastric tissue.
authors.affiliation: Department of Physiology, Xuzhou Medical College, Xuzhou, Jiangsu, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Cui
authors.forename: Cheng-Jie
authors.initials: CJ
authors.lastname: Song
authors.forename: Jin-Song
authors.initials: JS
authors.lastname: Bian
authors.forename: Anna
authors.initials: A
authors.lastname: Sparatore
authors.forename: Piero Del
authors.initials: PD
authors.lastname: Soldato
authors.forename: Xin-Yu
authors.initials: XY
authors.lastname: Wang
authors.forename: Chang-Dong
authors.initials: CD
authors.lastname: Yan
mesh_terms: D000818:Animals; D001241:Aspirin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D015232:Dinoprostone / Q000378:metabolism; D004220:Disulfides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000737:chemistry*; D008297:Male; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D014969:Xanthine Oxidase / Q000235:genetics / Q000378:metabolism
chemical_list: C577776:2-acetyloxybenzoic acid 4-(3-thioxo-3H-1,2-dithiol-5-yl)phenyl ester; D003692:Delayed-Action Preparations; D004220:Disulfides; D010750:Phosphoproteins; C079789:neutrophil cytosol factor 67K; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D014969:Xanthine Oxidase; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D005978:Glutathione; D015232:Dinoprostone; D001241:Aspirin; D006862:Hydrogen Sulfide