Mechanisms involved in the gastroprotective activity of esculin on acute gastric lesions in mice.
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.
Rios
Emiliano Ricardo Vasconcelos
ER
Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Rua Coronel Nunes de Melo, 1127, Brazil. emilianovasconcelos@yahoo.com.br
Rocha
Nayrton Flávio Moura
NF
Venâncio
Edith Teles
ET
Moura
Brinell Arcanjo
BA
Feitosa
Mariana Lima
ML
Cerqueira
Gilberto Santos
GS
Soares
Pedro Marcos Gomes
PM
Woods
David John
DJ
de Sousa
Francisca Cléa Florenço
FC
Leal
Luzia Kalyne Almeida Moreira
LK
Fonteles
Marta Maria de França
MM
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
D005765:Gastrointestinal Agents; D004929:Esculin