ABSTRACT
The aim of this experimental study was to investigate the effect of diclofenac sodium and ketoprofen, two non-steroidal anti-inflammatory drugs (NSAIDs) with different excretion pathways, and the role of other enteric factors during simultaneous administration of these drugs on the development of mucosal lesions of the small intestine in canines. Twenty-five animals were divided into three groups. Group I included 10 canines, 5 with diclofenac sodium (group Ia) and 5 with ketoprofen administration (group Ib). Group II included 5 animals in which a segment of ileum was surgically isolated from the rest of the small intestine. Group III included 10 animals in two subgroups of 5; a segment of ileum was surgically isolated in both subgroups; groups IIIa received diclofenac and group IIIb ketoprofen. Histological examination of the specimens taken revealed macroscopic and microscopic mucosal lesions in 5/5 animals in group Ia, whereas none of the 5 animals in group Ib had any lesions. Group II did not reveal any mucosal lesions. Three out of 5 animals (60%) administered diclofenac in group IIIa had intestinal mucosal lesions, but none of the 5 revealed lesions in the isolated loop of ileum. No lesions were observed in the isolated loop or in the rest of the intestinal mucosa in the animals in group IIIb. Our results suggest that NSAIDs produce intestinal mucosal lesions not only when administered per mouth but also after intramuscular administration. Diclofenac, unlike ketoprofen, was responsible for the development of lesions in the intestinal mucosa. The role of drugs and/or their metabolites in the intestine and certain other factors must still be determined.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/toxicity , Diclofenac/toxicity , Intestine, Small/drug effects , Intestine, Small/pathology , Ketoprofen/toxicity , Animals , Dogs , Intestinal Mucosa/drug effects , Intestinal Mucosa/pathologyABSTRACT
The aim of this study was to determine the effectiveness of highly selective vagotomy (HSV) or misoprostol, a prostaglandin E1 (PGE1) analog, for protecting the gastroduodenal mucosa (GDM) from the effects of diclofenac sodium (DS). Fifty mongrel dogs were randomly allocated to five groups. HSV alone was performed in group I dogs (controls) to standardize the operation. DS was given intramuscularly for 12 consecutive days to the group II dogs, whereas in the group III dogs HSV was performed, followed a month later by DS administration, as in group II. DS was given in combination with misoprostol for 12 days to the group IV dogs. HSV was performed on the group V dogs, and a month later DS and misoprostol were given, as in group IV. After sacrificing the animals the GDM was examined for macroscopic and histologic lesions. Statistical analysis was made by Fisher's exact test. HSV alone did not protect the gastric or duodenal mucosa from the effects of DS (p = 0.474 and p = 0.62, respectively). Misoprostol alone also did not offer significant protection to the gastric or the duodenal mucosa (p = 0.08 and p = 0.65, respectively). The combination of HSV plus misoprostol protected the gastric mucosa (group V, p = 0.007) but not the duodenal mucosa (group V, p = 0.08). Hence HSV or misoprostol alone offers no protection to the GDM from the effects of DS. The combination of HSV and misoprostol offers significant protection only to gastric mucosa. Enhancement of the mucosal defense mechanisms combined with strong reduction of gastric acidity may offer adequate protection to gastric mucosa from the effects of nonsteroidal antiinflammatory drugs.
