title: Pharmacological evidence for the participation of NO-cGMP-KATP pathway in the gastric protective effect of curcumin against indomethacin-induced gastric injury in the rat.
abstract: 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 (3-300mg/kg, p.o.) or omeprazole (30mg/kg, p.o.) 30min before indomethacin insult (30mg/kg, p.o.). Other groups of rats were administered L-NAME (70mg/kg, i.p.; inhibitor of nitric oxide synthase), ODQ (10mg/kg, i.p.; inhibitor of soluble guanylate cyclase) or glibenclamide (1mg/kg, i.p.; blocker of ATP-sensitive potassium (KATP) channels) 30min before curcumin (30mg/kg, p.o.). 3h 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.
authors.affiliation: Departamento de Farmacología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México, D.F., México.
authors.forename: Nadia Estela
authors.initials: NE
authors.lastname: Díaz-Triste
authors.affiliation: Departamento de Farmacología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México, D.F., México.
authors.forename: Martha Patricia
authors.initials: MP
authors.lastname: González-García
authors.affiliation: Unidad Académica Multidisciplinaria Reynosa Aztlán, Universidad Autónoma de Tamaulipas, Reynosa, Tamaulipas, México.
authors.forename: Juan Miguel
authors.initials: JM
authors.lastname: Jiménez-Andrade
authors.affiliation: Departamento de Farmacología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México, D.F., México.
authors.forename: Gilberto
authors.initials: G
authors.lastname: Castañeda-Hernández
authors.affiliation: Laboratorio de Farmacología, Programa Institucional en Biomedicina Molecular, Escuela Nacional de Medicina y Homeopatía del Instituto Politécnico Nacional, Guillermo Massieu Helguera no. 239, Fraccionamiento "La Escalera", Ticomán, C.P. 07320 México, D.F., México. Electronic address: achavezp@ipn.mx.
authors.forename: Aracely Evangelina
authors.initials: AE
authors.lastname: Chávez-Piña
mesh_terms: D000818:Animals; D003474:Curcumin / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism*; D019610:Cytoprotection / Q000187:drug effects; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D007213:Indomethacin / Q000009:adverse effects*; D054086:KATP Channels / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D013270:Stomach / Q000166:cytology / Q000187:drug effects* / Q000293:injuries
chemical_list: D054086:KATP Channels; D009573:Nitrites; D009569:Nitric Oxide; D006152:Cyclic GMP; D003474:Curcumin; D007213:Indomethacin
keywords: Curcumin; Gastric injury; Guanylate cyclase; Indomethacin; Nitric oxide; Potassium channel