Satoh H, Kondo R, Shinoda T, Idaka S, Ishigami K, Shiotani S
Department of Veterinary Pharmacology, Faculty of Agriculture, Tottori University, Tottori, Japan.
J Physiol Pharmacol. 2016 Aug;67(4):563-573.
Recent progress in endoscopic techniques has revealed that non-steroidal anti-inflammatory drugs (NSAIDs) often cause ulcers in the small intestine in humans, but effective therapy is not available at present. In the present study, we investigated the effects of feeding condition and the amount of dietary fiber (DF) in the diet on the formation of gastrointestinal ulcers induced by NSAIDs in dogs. Several types of diets containing various percentages of DF were given to dogs. Indomethacin (1 or 3 mg/kg, p.o.), ketoprofen (2 mg/kg, s.c.), or fulnixin (1 mg/kg, s.c.) was administered once daily at 10 a.m. after a morning meal or without a morning meal (fasted condition) for 3 - 7 days. Gastrointestinal lesions were examined 24 h after the final dose of the drugs. When indomethacin (3 mg/kg) was administered after a morning meal (fed condition) for 7 days, it produced many lesions in the small intestine. However, when it was given in the fasted condition without the morning meal, the lesions were markedly decreased. All the NSAIDs given after feeding of regular dry food containing 6% DF once a day for 3 days produced many lesions in the small intestine. The lesions were decreased or increased in dogs given prescription diets containing low DF (1.1%) and high DF (15.4%), respectively. Furthermore, lesions were not observed in dogs given canned diet containing very low DF (< 0.1%), whereas lesions appeared again in dogs given canned diet supplemented with cellulose (3 or 10%) but not with pectin (10%). These results suggested that both feeding condition and insoluble DF, such as cellulose in the diet, play an important role in the formation of NSAID-induced small intestinal lesions, and that a diet with no or low amounts of DF may decrease gastrointestinal side-effects associated with the use of NSAIDs.
内镜技术的最新进展表明，非甾体抗炎药（NSAIDs）在人类中常导致小肠溃疡，但目前尚无有效的治疗方法。在本研究中，我们调查了喂养条件和饮食中膳食纤维（DF）的量对NSAIDs诱导的犬胃肠道溃疡形成的影响。给犬喂食含有不同百分比DF的几种类型的饮食。吲哚美辛（1或3mg/kg，口服）、酮洛芬（2mg/kg，皮下注射）或氟尼辛（1mg/kg，皮下注射）在早餐后上午10点或不进食早餐（禁食状态）下每天给药一次，持续3至7天。在最后一剂药物给药24小时后检查胃肠道病变。当吲哚美辛（3mg/kg）在早餐后（进食状态）给药7天时，在小肠中产生了许多病变。然而，当在禁食状态下不进食早餐给药时，病变明显减少。所有NSAIDs在每天喂食一次含6%DF的常规干粮3天后给药，均在小肠中产生了许多病变。分别给予含低DF（1.1%）和高DF（15.4%）的处方饮食的犬，病变减少或增加。此外，给予含极低DF（<0.1%）的罐装饮食的犬未观察到病变，而给予补充纤维素（3%或10%）但不补充果胶（10%）的罐装饮食的犬再次出现病变。这些结果表明，喂养条件和饮食中的不溶性DF，如纤维素，在NSAIDs诱导的小肠病变形成中起重要作用，并且无DF或低DF的饮食可能会减少与使用NSAIDs相关的胃肠道副作用。
