Protection of the Gastroduodenal Mucosa from the Effects of Diclofenac Sodium: Role of Highly Selective Vagotomy and Misoprostol

Abstract

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.

Gastroprotectants in small animal veterinary practice – a review of the evidence. Part 1: cyto‐protective drugs

“…In dogs, a dose of 8 to 20 μg/kg misoprostol every 6 hours alone was not found to protect the gastro‐duodenal mucosa from injury induced by a dose of 1 mg/kg diclofenac sodium intramuscularly every 24 hours, though it offered gastric protection when combined with highly selective vagotomy (Giannoukas et al . ). In a more recent study (Roškar et al .…”

“…This was not the case for misoprostol and diclofenac (Giannoukas et al . ), and the evidence for prevention of injury with meloxicam use was tenuous (Roškar et al . ).…”

“…Despite the apparent positive effects of misoprostol in prevention of aspirin-induced gastrointestinal injury, this has not been confirmed with other NSAIDs. In dogs, a dose of 8 to 20 μg/kg misoprostol every 6 hours alone was not found to protect the gastro-duodenal mucosa from injury induced by a dose of 1 mg/ kg diclofenac sodium intramuscularly every 24 hours, though it offered gastric protection when combined with highly selective vagotomy (Giannoukas et al 1996). In a more recent study (Roškar et al 2011), a dose of 100 μg/kg misoprostol orally every 8 hours did not result in improvement of prostaglandin serum concentration when administered with meloxicam, compared to dogs that received meloxicam alone.…”

A comparative experimental study of the effects of diclofenac and ketoprofen on the small-bowel mucosa of canines

“…Their weight ranged from 8 to 25 kg. Dogs were chosen because of (a) the necessity for fairly large animals, (b) the similarity of the dog's digestive system to that of man, and (c) its particular sensitivity to NSAIDs [8].…”

Anti-inflammatory, antinociceptive and ulcerogenic activity of a zinc-diclofenac complex in rats

“…Thus, some approaches have been devised to reduce the incidence of these side effects, including the use of different routes of administration (5), H 2 receptor antagonists (6), pro-drugs (7), omeprazole and sucralfate (8), misoprostol (9), and selective cyclooxygenase 2 inhibitors (10).…”