RESUMEN
The leaves of Mikania (Asteraceae) species are used in folk medicine as antispasmodic, antiulcerogenic and antirheumatic agents. Phytochemical screening of the crude hydroalcoholic 70% extract (CHE) of Mikania laevigata Shultz Bip. revealed coumarins, terpenes and organic acids. Antiulcerogenic activity of CHE was evaluated, employing different experimental models in rats, to discern the pharmacological mechanism of action. Both the antisecretory and the cytoprotection hypothesis were evaluated. The crude hydroalcoholic extract (1000 mg/kg body wt., vo) decreased the ulcerative lesion index produced by indomethacin, ethanol, stress and reserpine in rats by 85%, 93%, 82% and 50%, respectively. In the pyloric ligation model, a decrease of hydrogenionic concentration (53%) was observed, suggesting that the pharmacological mechanism has a relationship to antisecretory activity. The antisecretory mechanisms of CHE and the coumarin isolated from M. laevigata were confirmed by acid hypersecretion induced by histamine, pentagastrin and bethanechol. Duodenal administration of CHE (1000 mg/kg body wt.) and coumarin (100 mg/kg body wt.) inhibited only the gastric acid secretion produced by bethanecol. These results suggest that both CHE and coumarin may influence the secretion control mediated by the parasympathetic system.
Asunto(s)
Antiulcerosos/uso terapéutico , Úlcera Duodenal/prevención & control , Mikania , Fitoterapia , Extractos Vegetales/uso terapéutico , Animales , Antiulcerosos/administración & dosificación , Anticoagulantes/administración & dosificación , Anticoagulantes/uso terapéutico , Cumarinas/administración & dosificación , Cumarinas/uso terapéutico , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Úlcera Duodenal/inducido químicamente , Etanol , Indometacina , Masculino , Extractos Vegetales/administración & dosificación , Hojas de la Planta , Ratas , Ratas Wistar , Reserpina , Estrés FisiológicoRESUMEN
The protective effect of a whey protein concentrate (WPC) was studied in three models of stomach ulcerative lesions induction: subcutaneous injection of indomethacin, and stress induced by either intraperitoneal injection of reserpine, or immobilization and holding in the cold (4 degrees C, 2 hours). Adult Wistar rats (300-400 g) were used for acute (single-dose), repetitive, or subchronic (10 days) administration of WPC prior to treatment with the ulcerogenic factors. The best protection was achieved in the indomethacin model for repetitive and subchronic experiments, reaching 50.1% and 44%, respectively, inhibition of the ulcerative lesions, which was significant at 1% probability (P <.01). For the immobilization and cold model, maximum inhibition by WPC was 22.1%, and that for the reserpine model was 23.8%. In both models the inhibition was not significant (P >.05) compared with saline (negative control).
Asunto(s)
Antiulcerosos/farmacología , Mucosa Gástrica/efectos de los fármacos , Proteínas de la Leche/farmacología , Úlcera Gástrica/prevención & control , Animales , Antiinflamatorios no Esteroideos/toxicidad , Antiulcerosos/uso terapéutico , Bovinos , Cimetidina/farmacología , Cimetidina/uso terapéutico , Modelos Animales de Enfermedad , Mucosa Gástrica/patología , Inmovilización , Indometacina/toxicidad , Inyecciones Intraperitoneales , Inyecciones Subcutáneas , Masculino , Leche/química , Proteínas de la Leche/uso terapéutico , Distribución Aleatoria , Ratas , Ratas Wistar , Reserpina/farmacología , Úlcera Gástrica/inducido químicamente , Proteína de Suero de LecheRESUMEN
The purpose of this research was to test the ability of a whey protein concentrate (WPC) to inhibit gastric mucosal ulcerative lesions caused by oral administration to rats of absolute ethanol. Acute administration (single doses) of WPC resulted in 41% inhibition of the ulcerative lesion index (ULI), and 73% inhibition was obtained with repetitive doses. In a 10-days subchronic treatment study, the inhibition was 64%, all relative to a saline treatment (negative control). Alkylation of sulfhydryl compounds by subcutaneous injection of N-ethylmaleimide essentially eliminated the WPC protection. Treating the rats with an intraperitoneal injection of butathionine sulfoximine, which inhibits glutathione synthesis, reduced WPC protection to 35% and 52% for single and double doses, respectively. Taken as a whole, the results indicate that WPC does protect gastric mucosa from ethanol damage and that the protection depends on sulfhydryl compounds present in the WPC, including its capacity to stimulate glutathione synthesis.