title: Carbenoxolone gastroprotective mechanism: participation of nitric oxide/(c) GMP/K(ATP)  pathway in ethanol-induced gastric injury in the rat.
abstract: Carbenoxolone, a semi-synthetic triterpenoid, exhibits gastroprotective activity related to the participation of nitric oxide (NO); however, the complete NO/(c) GMP/K(ATP) channels pathway for carbenoxolone is unknown. Therefore the aim of this study was to examine the NO/(c) GMP/K(ATP) channels pathway as the gastroprotective mechanism of carbenoxolone in the ethanol-induced gastric injury model in the rat. Oral administration of carbenoxolone (30 mg/kg, p.o.) exhibited gastroprotective effect against ethanol-induced gastric injury in rats. Pretreatment with N(G) -nitro-l-arginine methyl ester (L-NAME, 70 mg/kg, i.p.); 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ, guanylate cyclase inhibitor, 10 mg/kg, i.p.); or glibenclamide (K(ATP) channels inhibitor, 1 mg/kg, i.p.) reversed the gastroprotective effect of carbenoxolone for ethanol-induced gastric injury. Furthermore, gastric prostaglandins and NO levels increased after carbenoxolone administration in ethanol-induced gastric injury in rats. In conclusion, our results suggest that the increase of NO levels in gastric tissue after pretreatment with carbenoxolone activates the NO/(c)GMP/K(ATP) channels pathway, the principal gastroprotective mechanism of carbenoxolone.
authors.affiliation: Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, Ciudad Universitaria. Coyoacán 04510, México.
authors.forename: Aracely Evangelina
authors.initials: AE
authors.lastname: Chávez-Piña
authors.forename: Gabriela Rubí
authors.initials: GR
authors.lastname: Tapia-Álvarez
authors.forename: Adelfo
authors.initials: A
authors.lastname: Reyes-Ramínrez
authors.forename: Andrés
authors.initials: A
authors.lastname: Navarrete
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D002229:Carbenoxolone / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity*; D054086:KATP Channels / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D000897:Anti-Ulcer Agents; D054086:KATP Channels; D011453:Prostaglandins; D009569:Nitric Oxide; D000431:Ethanol; D006152:Cyclic GMP; D002229:Carbenoxolone