INDOMETHACIN DAMAGE TO RAT GASTRIC MUCOSA IS MARKEDLY DEPENDENT ON LUMINAL pH

Abstract

1. There is good evidence that acid is a prerequisite for aspirin induced gastric mucosal damage; however, there is inconsistent information available for non-salicylate NSAID. The present study examines the effect of gastric luminal pH on indomethacin-induced gastric mucosal damage. 2. Macroscopic gastric mucosal damage induced by indomethacin (40 mg/kg) or vehicle, administered intraduodenally to male pylorus-ligated rats (n = 5-10/group), was assessed at four different levels of luminal pH (2,4,5.5 and 7) by means of digital planimetry. 3. There was a marked difference in the extent of damage induced by indomethacin at the different luminal pH levels (P = 0.001). There was no difference between the percentage of haemorrhagic lesions at pH 2 and 4 (P > 0.05), nor between pH 5.5 and 7 (P > 0.05). However, the damage at the high levels of luminal acidity (pH 2 and 4) was strikingly different from that at pH 5.5 and 7 (P < 0.05). 4. Gastric mucosal damage induced by indomethacin, a non-salicylate NSAID, is augmented by the presence of high concentration of acid in the gastric lumen. The main finding, that indomethacin injury is markedly less above pH 4, may have clinical implications in the prevention of NSAID-induced mucosal injury.

Influence of sex and Helicobacter pylori on development and healing of gastroduodenal lesions in non-steroidal anti-inflammatory drug users

“…42 These subsequently progress by a process of deepening under the influence of acid peptic attack in the stomach or other factors such as infection in the small intestine. 42 In the stomach, it appears necessary to reach a pH minimum of four to prevent this acid peptic attack, 45 an observation consistent with the greater effect of omeprazole than ranitidine on both ulcers and erosions. Other studies suggest that higher than normal doses of H 2 antagonists are of greater efficacy than seen in our studies.…”

Intragastric acid control in non‐steroidal anti‐inflammatory drug users: comparison of esomeprazole, lansoprazole and pantoprazole

“…4 Also, it appears that NSAID-induced gastric mucosal damage may be greater when pH is <4.0. 5 The clinical correlate of the pivotal role of gastric acid in the development of gastroduodenal mucosal injury is that proton pump inhibitor (PPI) co-therapy has been shown to heal, maintain healing and reduce the risk of developing NSAIDrelated ulcers [6][7][8][9][10][11] and to decrease NSAID-related upper gastrointestinal (GI) symptoms. 8,9,12,13 Practice guidelines often recommend co-prescribing an acid inhibitor, such as a PPI, with NSAIDs in patients at risk of developing GI complications.…”

High Serum Pepsinogen I and beta Helicobacter pylori Infection Are Risk Factors for Aspirin-Induced Gastroduodenal Injury

“…Gastric hyperchlorhydria is an essential pathogen for upper GI mucosal injury, including NSAIDs/aspirin-associated gastroduodenal damage [7,8]. Traditional measurement of gastric acidity by aspirating gastric juice is invasive and troublesome; these factors restrict its clinical use.…”