Nonsteroidal anti‐inflammatory drugs induce hypermotilinemia and disturbance of interdigestive migrating contractions in instrumented dogs

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) induce gastric ulcers due to inhibition of prostaglandin production. Prostaglandins have an influence on physiological gastrointestinal motility, but the relationships between NSAID-induced gastric ulcer, gastrointestinal motility and motilin are unknown. Fifteen dogs were allocated randomly to three groups in which either gelatin, meloxicam or indomethacin was administered. Fecal occult blood and gastrointestinal motility were monitored continuously for 6 days. In addition, analyses of the plasma motilin concentration, gastrointestinal endoscopy and gastric emptying, and detection of motilin cells were performed. Gastrointestinal motility was disturbed in the indomethacin group, presenting as disappearance of interdigestive migrating contractions (IMCs) 3 days before gastric ulcers were detected. Delayed gastric emptying and hypermotilinemia were observed significantly more often in the indomethacin group compared with the other groups. Motilin cell-crypt/villi ratio in the indomethacin group significantly decreased in the duodenum and jejunum, compared with the other groups. No significant changes in any tests were observed in the meloxicam group, when compared with the gelatin group. These findings suggest that the disturbance of IMCs caused by hypermotilinemia, with changes in motilin cell distribution, and delayed gastric emptying induced by indomethacin may contribute to the development of gastric ulcers.

Mechanisms of gastroprotective effect of eugenol in indomethacin‐induced ulcer in rats

“…This is due to improved gastric mucosal blood flow that enhances tissue oxygen and nutrient delivery allowing resistance to ulcer injury. Also, K ATP channel modulation prevents gastric hypermotility that may contribute to the ulcerogenic effect of NSAIDs (Narita et al, 2006).…”

Melatonin Attenuates Noise Stress-induced Gastrointestinal Motility Disorder and Gastric Stress Ulcer: Role of Gastrointestinal Hormones and Oxidative Stress in Rats

“…The results show that motilin is connected with ulcer and GI motility induced by nonsteroidal anti-inflammatory drugs. 52 The motilin level in rats is also related to ulcerated antral mucosa tissue. 53 Enterochromaffin cells in GI tract could secrete MT and motilin.…”

Single-dose safety and pharmacokinetic evaluation of fluorocoxib A: pilot study of novel cyclooxygenase-2-targeted optical imaging agent in a canine model

“…HPLC analysis with ultraviolet detection was performed on a Waters 2695 Separation Module in-line with a Waters 2487 Dual Wavelength Absorbance detector to confirm the identity and purity of the synthesized fluorocoxib A product. 26,27 We used a fluorescence detector set at 581 nm in our HPLC system. The free dye and fluorocoxib A are distinguishable by their retention times (2.5 and 5.1 min, respectively) under the HPLC conditions used.…”

“…26 Ester and amide derivatives of indomethacin, such as fluorocoxib A, show selective COX-2 inhibition, resulting in substantial anti-inflammatory activity with markedly reduced GI toxicity in rodents. 27 It is generally accepted that efficacy of NSAIDs is mainly dependent on COX-2 inhibition, whereas adverse events related to the GI tract (irritation and ulceration of stomach) and inhibition of hemostatic mechanisms are mainly related to COX-1 inhibition.…”