TY - JOUR
T1 - Carbenoxolone gastroprotective mechanism
T2 - Participation of nitric oxide/ cGMP/K ATP pathway in ethanol-induced gastric injury in the rat
AU - Chávez-Piña, Aracely Evangelina
AU - Tapia-Álvarez, Gabriela Rubí
AU - Reyes-Ramínrez, Adelfo
AU - Navarrete, Andrés
PY - 2011/12
Y1 - 2011/12
N2 - Carbenoxolone, a semi-synthetic triterpenoid, exhibits gastroprotective activity related to the participation of nitric oxide (NO); however, the complete NO/ cGMP/K ATP channels pathway for carbenoxolone is unknown. Therefore the aim of this study was to examine the NO/ cGMP/K ATP channels pathway as the gastroprotective mechanism of carbenoxolone in the ethanol-induced gastric injury model in the rat. Oral administration of carbenoxolone (30mg/kg, p.o.) exhibited gastroprotective effect against ethanol-induced gastric injury in rats. Pretreatment with N G-nitro-l-arginine methyl ester (L-NAME, 70mg/kg, i.p.); 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ, guanylate cyclase inhibitor, 10mg/kg, i.p.); or glibenclamide (K ATP channels inhibitor, 1mg/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/ cGMP/K ATP channels pathway, the principal gastroprotective mechanism of carbenoxolone.
AB - Carbenoxolone, a semi-synthetic triterpenoid, exhibits gastroprotective activity related to the participation of nitric oxide (NO); however, the complete NO/ cGMP/K ATP channels pathway for carbenoxolone is unknown. Therefore the aim of this study was to examine the NO/ cGMP/K ATP channels pathway as the gastroprotective mechanism of carbenoxolone in the ethanol-induced gastric injury model in the rat. Oral administration of carbenoxolone (30mg/kg, p.o.) exhibited gastroprotective effect against ethanol-induced gastric injury in rats. Pretreatment with N G-nitro-l-arginine methyl ester (L-NAME, 70mg/kg, i.p.); 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ, guanylate cyclase inhibitor, 10mg/kg, i.p.); or glibenclamide (K ATP channels inhibitor, 1mg/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/ cGMP/K ATP channels pathway, the principal gastroprotective mechanism of carbenoxolone.
KW - Carbenoxolone
KW - Cyclic GMP
KW - Gastric injury
KW - Nitric oxide
KW - Potassium channels
UR - http://www.scopus.com/inward/record.url?scp=80054909103&partnerID=8YFLogxK
U2 - 10.1111/j.1472-8206.2010.00897.x
DO - 10.1111/j.1472-8206.2010.00897.x
M3 - Artículo
SN - 0767-3981
VL - 25
SP - 717
EP - 722
JO - Fundamental and Clinical Pharmacology
JF - Fundamental and Clinical Pharmacology
IS - 6
ER -