RESUMO
Antisecretory drugs such as histamine H2-receptor antagonists and proton pump inhibitors are commonly used for the treatment of upper gastrointestinal mucosal lesions induced by nonsteroidal anti-inflammatory drugs (NSAIDs). However, it has recently been reported that these drugs exacerbate NSAID-induced small intestinal lesions in rats. Unfortunately, there are few effective agents for the treatment of this complication. We examined the effects of mucosal protective agents (MPAs) (misoprostol, irsogladine, and rebamipide) and mucin of porcine stomach on diclofenac-induced intestinal lesions and the exacerbation of the lesions by ranitidine or omeprazole. The effects of the drugs on intestinal motility and mucus distribution/content were also examined. Male Wistar rats (180-220 g) were used. Each drug was administered orally under fed conditions. Diclofenac (1-10 mg/kg) produced multiple lesions in the small intestine dose-dependently. Both ranitidine (30 mg/kg) and omeprazole (100 mg/kg) significantly increased the intestinal lesions induced by low doses (3 and 6 mg/kg) of diclofenac. Misoprostol (0.03-0.3 mg/kg), irsogladine (3-30 mg/kg), and rebamipide (30-300 mg/kg), as well as mucin (30-300 mg/kg) inhibited the formation of intestinal lesions caused by a high dose (10 mg/kg) of diclofenac alone and prevented the exacerbation of diclofenac-induced lesions by antisecretory drugs. Diclofenac (10 mg/kg) markedly increased the intestinal motility and decreased the mucosal mucus, and the decrease of mucus was significantly inhibited by the MPAs. These results indicate the usefulness of the MPAs for the treatment of intestinal lesions induced by NSAIDs alone or by coadministration with antisecretory drugs, and suggest that mucus plays an important role in the protection of intestinal mucosa by the MPAs.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Antiulcerosos/efeitos adversos , Fármacos Gastrointestinais/uso terapêutico , Enteropatias/prevenção & controle , Mucosa Intestinal/efeitos dos fármacos , Intestino Delgado/efeitos dos fármacos , Substâncias Protetoras/uso terapêutico , Alanina/administração & dosagem , Alanina/análogos & derivados , Alanina/uso terapêutico , Animais , Antiulcerosos/uso terapêutico , Diclofenaco/efeitos adversos , Relação Dose-Resposta a Droga , Mucinas Gástricas/administração & dosagem , Mucinas Gástricas/uso terapêutico , Fármacos Gastrointestinais/administração & dosagem , Enteropatias/induzido quimicamente , Enteropatias/patologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Intestino Delgado/metabolismo , Intestino Delgado/patologia , Masculino , Misoprostol/administração & dosagem , Misoprostol/uso terapêutico , Muco/efeitos dos fármacos , Muco/metabolismo , Omeprazol/efeitos adversos , Omeprazol/uso terapêutico , Substâncias Protetoras/administração & dosagem , Inibidores da Bomba de Prótons/efeitos adversos , Inibidores da Bomba de Prótons/uso terapêutico , Quinolonas/administração & dosagem , Quinolonas/uso terapêutico , Ranitidina/efeitos adversos , Ranitidina/uso terapêutico , Ratos , Ratos Wistar , Sus scrofa , Triazinas/administração & dosagem , Triazinas/uso terapêuticoRESUMO
A double-blind, five phase, cross-over clinical trial was used to compare a mucin-based artificial saliva (Saliva Orthana) with its non-mucin base and water. Thirty patients, acting as their own controls, took part. Saliva Orthana offered significantly greater relief from xerostomia compared with its base or water, and was significantly better at relieving soreness than water. In terms of overall preference, it was ranked significantly higher than either alternative.