TY - JOUR
T1 - Pharmacological evidence for the participation of NO-cGMP-K ATP pathway in the gastric protective effect of curcumin against indomethacin-induced gastric injury in the rat
AU - Díaz-Triste, Nadia Estela
AU - González-García, Martha Patricia
AU - Jiménez-Andrade, Juan Miguel
AU - Castañeda-Hernández, Gilberto
AU - Chávez-Piña, Aracely Evangelina
N1 - Funding Information:
Authors acknowledge the support of National Polytechnic Institute with Projects SIP-20131157 and SIP-SNI-2011/01 , to the National Council for Science and Technology with Project CONACyT 178027 . Nadia Estela Díaz-Triste was a CONACyT fellow.
PY - 2014/5/5
Y1 - 2014/5/5
N2 - Curcumin, main compound obtained from rizhoma of Curcuma longa, shows antitumoral, antioxidant, anticarcinogenic and gastric protective properties. Recently, it has been demonstrated that curcumin exerts its gastric protective action due to an increase in gastric nitric oxide (NO) levels. However, it is unknown whether these increased NO levels are associated with activation of intracellular signaling pathways. Thus, the purpose of this study was to investigate the role of NO-cGMP-KATP pathway in the gastric protective effect of curcumin during indomethacin-induced gastric injury in the rat. Adult female Wistar rats were gavaged with curcumin (3-300 mg/kg, p.o.) or omeprazole (30 mg/kg, p.o.) 30 min before indomethacin insult (30 mg/kg, p.o.). Other groups of rats were administered L-NAME (70 mg/kg, i.p.; inhibitor of nitric oxide synthase), ODQ (10 mg/kg, i.p.; inhibitor of soluble guanylate cyclase) or glibenclamide (1 mg/kg, i.p.; blocker of ATP-sensitive potassium (KATP) channels) 30 min before curcumin (30 mg/kg, p.o.). 3 h after indomethacin administration, rats were sacrificed and gastric injury was evaluated by determining total damaged area. A sample of gastric tissue was harvested and processed to quantify organic nitrite levels. Curcumin significantly protected against indomethacin-induced gastric injury and this effect was comparable to gastroprotective effect by omeprazole. L-NAME, ODQ and glibenclamide significantly prevented the curcumin-mediated gastric protective effect in the indomethacin-induced gastric injury model. Furthermore, curcumin administration induced a significant increase in gastric nitric oxide levels as compared to vehicle administration. Our results show for the first time that curcumin activates NO/cGMP/KATP pathway during its gastro protective action.
AB - Curcumin, main compound obtained from rizhoma of Curcuma longa, shows antitumoral, antioxidant, anticarcinogenic and gastric protective properties. Recently, it has been demonstrated that curcumin exerts its gastric protective action due to an increase in gastric nitric oxide (NO) levels. However, it is unknown whether these increased NO levels are associated with activation of intracellular signaling pathways. Thus, the purpose of this study was to investigate the role of NO-cGMP-KATP pathway in the gastric protective effect of curcumin during indomethacin-induced gastric injury in the rat. Adult female Wistar rats were gavaged with curcumin (3-300 mg/kg, p.o.) or omeprazole (30 mg/kg, p.o.) 30 min before indomethacin insult (30 mg/kg, p.o.). Other groups of rats were administered L-NAME (70 mg/kg, i.p.; inhibitor of nitric oxide synthase), ODQ (10 mg/kg, i.p.; inhibitor of soluble guanylate cyclase) or glibenclamide (1 mg/kg, i.p.; blocker of ATP-sensitive potassium (KATP) channels) 30 min before curcumin (30 mg/kg, p.o.). 3 h after indomethacin administration, rats were sacrificed and gastric injury was evaluated by determining total damaged area. A sample of gastric tissue was harvested and processed to quantify organic nitrite levels. Curcumin significantly protected against indomethacin-induced gastric injury and this effect was comparable to gastroprotective effect by omeprazole. L-NAME, ODQ and glibenclamide significantly prevented the curcumin-mediated gastric protective effect in the indomethacin-induced gastric injury model. Furthermore, curcumin administration induced a significant increase in gastric nitric oxide levels as compared to vehicle administration. Our results show for the first time that curcumin activates NO/cGMP/KATP pathway during its gastro protective action.
KW - Curcumin
KW - Gastric injury
KW - Guanylate cyclase
KW - Indomethacin
KW - Nitric oxide
KW - Potassium channel
UR - http://www.scopus.com/inward/record.url?scp=84896936504&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2014.02.030
DO - 10.1016/j.ejphar.2014.02.030
M3 - Artículo
SN - 0014-2999
VL - 730
SP - 102
EP - 106
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1
ER -