title: Mechanisms involved in the gastroprotective activity of esculin on acute gastric lesions in mice.
abstract: This work describes the gastroprotective actions of esculin (6,7-dihydroxycoumarin-6-o-glucoside) against indomethacin- or ethanol-induced lesions and verifies the role of nitric oxide, ATP-dependent K(+) channels, prostaglandins, transient receptor potential vanilloid 1 and antioxidant effects in the gastroprotective mechanism of esculin in the ethanol-induced gastric lesion model. The intragastric administration of esculin at doses of 12.5, 25 and 50 mg/kg was able to protect the gastric mucosa against ethanol (0.2 mL/animal p.o.), and esculin at doses of 25 and 50 mg/kg protected against indomethacin-induced lesions (20mg/kg p.o.). Administration of l-NAME (10mg/kg i.p.), glibenclamide (10mg/kg i.p.) or indomethacin (10mg/kg p.o.), but not capsazepine (5mg/kg p.o.), was able to reduce the gastroprotection promoted by esculin (25mg/kg) on the ethanol-induced lesions. Measurements of nitrite, a NO metabolite, were increased in the group that was pretreated with esculin. In terms of antioxidant activity as a gastroprotective mechanism of esculin, the results show that pre-treatment with esculin decreased the amount of GSH, increased SOD activity, did not interfere with the CAT activity and decreased both the MPO activity and the MDA amount. In conclusion, pre-treatment with esculin confers significant gastroprotective and antioxidant activity and leads to a reduction in gastric injury; the mechanisms underlying these effects include stimulation of endogenous prostaglandins, nitric oxide synthesis, opening of K(ATP) channels and reduction of free radicals or modulation of antioxidant enzyme systems.
authors.affiliation: Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Rua Coronel Nunes de Melo, 1127, Brazil. emilianovasconcelos@yahoo.com.br
authors.forename: Emiliano Ricardo Vasconcelos
authors.initials: ER
authors.lastname: Rios
authors.forename: Nayrton Flávio Moura
authors.initials: NF
authors.lastname: Rocha
authors.forename: Edith Teles
authors.initials: ET
authors.lastname: Venâncio
authors.forename: Brinell Arcanjo
authors.initials: BA
authors.lastname: Moura
authors.forename: Mariana Lima
authors.initials: ML
authors.lastname: Feitosa
authors.forename: Gilberto Santos
authors.initials: GS
authors.lastname: Cerqueira
authors.forename: Pedro Marcos Gomes
authors.initials: PM
authors.lastname: Soares
authors.forename: David John
authors.initials: DJ
authors.lastname: Woods
authors.forename: Francisca Cléa Florenço
authors.initials: FC
authors.lastname: de Sousa
authors.forename: Luzia Kalyne Almeida Moreira
authors.initials: LK
authors.lastname: Leal
authors.forename: Marta Maria de França
authors.initials: MM
authors.lastname: Fonteles
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004929:Esculin / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000378:metabolism; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D015227:Lipid Peroxidation; D008297:Male; D051379:Mice; D013270:Stomach / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology
chemical_list: D005765:Gastrointestinal Agents; D004929:Esculin