RESUMEN
Geraniol is an acyclic monoterpene alcohol commonly used as a flavoring agent. The present study was undertaken to investigate antiulcerogenic effects of geraniol and to determine the possible mechanisms involved in this action. In the model of the ethanol-induced ulcer, treatment of rats with geraniol by oral route significantly inhibited gastric lesions by 70 % (7.50 mg/kg) to 99 % (200 mg/kg). Analysis of the gastric tissue of rats treated with geraniol (7.50 mg/kg) revealed that total glutathione content levels (GSH) increased and levels of myeloperoxidase (MPO) decreased in the gastric mucosa. Oral treatment with geraniol significantly decreased the number of ulcerative lesions induced by ischemia/reperfusion injury by 71 % and the duodenal ulcers induced by cysteamine by 68 %. The action of geraniol was mediated by the activation of defensive mucosa-protective factors such as the nitric oxide (NO) pathway, endogenous prostaglandins, increased mucus production, increased sulfhydryl compounds, antioxidant properties and the stimulation of calcitonin gene-related peptide (CGRP) release through the activation of transient receptor potential vanilloid (TRPV). The multifaceted gastroprotective mechanisms of geraniol represent a promising option for the treatment of gastric and duodenal mucosa injury.
Asunto(s)
Antiulcerosos/uso terapéutico , Úlcera Duodenal/tratamiento farmacológico , Aromatizantes/uso terapéutico , Úlcera Gástrica/tratamiento farmacológico , Terpenos/uso terapéutico , Monoterpenos Acíclicos , Animales , Antiulcerosos/farmacología , Cisteamina , Úlcera Duodenal/etiología , Úlcera Duodenal/patología , Duodeno/efectos de los fármacos , Duodeno/patología , Etanol , Aromatizantes/farmacología , Mucosa Gástrica/metabolismo , Glutatión/metabolismo , Masculino , Moco/metabolismo , Óxido Nítrico/metabolismo , Peroxidasa/metabolismo , Píloro/cirugía , Ratas , Ratas Wistar , Daño por Reperfusión , Estómago/efectos de los fármacos , Estómago/patología , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patología , Terpenos/farmacologíaRESUMEN
Allergic asthma is a chronic inflammatory airway disease with increasing prevalence around the world. Current asthma therapy includes drugs that usually cause significant side effects, justifying the search for new anti-asthmatic drugs. Curine is a bisbenzylisoquinoline alkaloid that modulates calcium influx in many cell types; however, its anti-allergic and putative toxic effects remain to be elucidated. Our aim was to investigate the effects of curine on eosinophil activation and airway hyper-responsiveness (AHR) and to characterize its potential toxic effects. We used a mouse model of allergic asthma induced by sensitization and challenge with ovalbumin (OVA) to evaluate the anti-allergic effects of oral treatment with curine. The oral administration of curine significantly inhibited eosinophilic inflammation, eosinophil lipid body formation and AHR in animals challenged with OVA compared with animals in the untreated group. The curine treatment also reduced eotaxin and IL-13 production triggered by OVA. Verapamil, a calcium channel antagonist, had similar anti-allergic properties, and curine pre-treatment inhibited the calcium-induced tracheal contractile response ex-vivo, suggesting that the mechanism by which curine exerts its effects is through the inhibition of a calcium-dependent response. A toxicological evaluation showed that orally administered curine did not significantly alter the biochemical, hematological, behavioral and physical parameters measured in the experimental animals compared with saline-treated animals. In conclusion, curine showed anti-allergic activity through mechanisms that involve inhibition of IL-13 and eotaxin and of Ca(++) influx, without inducing evident toxicity and as such, has the potential for the development of anti-asthmatic drugs.