Gastroenterology

Gastroenterology

Volume 102, Issue 5, May 1992, Pages 1605-1611
Gastroenterology

Effects of nonsteroidal anti-inflammatory drugs and misoprostol on gastroduodenal epithelial proliferation in arthritis

https://doi.org/10.1016/0016-5085(92)91720-OGet rights and content

Abstract

In this study, quantitation of the epithelial proliferation status of gastric glands and duodenal crypts was performed using endoscopic biopsy specimens from patients with rheumatological conditions requiring long-term anti-inflammatory and analgesic therapy, testing the hypothesis that long-term administration of nonsteroidal anti-inflammatory drugs (NSAIDs) may lead to enhanced epithelial cell proliferation in the stomach and duodenum. After a 1-week washout period from NSAID administration, specimens were taken from endoscopically normal gastric antrum and duodenum, and microdissection was used to quantitate mitoses in these sites. Endoscopy and biopsy were then repeated after 2 weeks of NSAID administration, during which patients received in addition either the prostaglandin E1 analogue misoprostol (10 patients) or a placebo (10 patients). Mitotic counts in gastric glands increased similarly and significantly in the two groups from (mean ± SEM) 4.45 ± 0.57 to 7.69 ± 1.08 (P < 0.001) in the NSAID + placebo-treated group and from 4.31 ± 0.53 to 7.68 ± 1.08 (P = 0.006) in the NSAID + misoprostol-treated group. Similar changes took place in the duodenal crypts, from 5.44 ± 0.68 to 8.60 ± 1.28 (P = 0.013) in the NSAID + placebo-treated group and from 4.68 ± 0.56 to 6.35 ± 0.63 (P = 0.011) in the NSAID + misoprostoltreated group. NSAIDs increased the proportion of glands and crypts with bifid or more complex architectural forms. In a small group of patients, misoprostol alone did not alter mitotic rate in glands or crypts over 4 weeks. Thus, NSAIDs increase the rate of proliferation in endoscopically normal gastric and duodenal epithelium of patients with arthritis. This may form one of the mechanisms underlying gastric and duodenal adaptation to NSAIDs.

References (38)

  • RA Goodlad et al.

    Morphometry and cell proliferation in endoscopic biopsies: evaluation of a technique

    Gastroenterology

    (1991)
  • GL Eastwood et al.

    Effect of chronic aspirin ingestion on epithelial proliferation in rat fundus, antrum and duodenum

    Gastroenterology

    (1982)
  • H Kuwayama et al.

    Effects of water immersion restraint stress and chronic indomethacin ingestion on gastric antral and fundic epithelial proliferation

    Gastroenterology

    (1985)
  • CJ Shorrock et al.

    The effects of indomethacin on gastroduodenal morphology and mucosal pH gradient in the healthy human stomach

    Gastroenterology

    (1990)
  • DY Graham et al.

    Prevention of NSAID-induced gastric ulcer with misoprostol: multi-centre, double-blind, placebo-controlled trial

    Lancet

    (1988)
  • ED Jacobson

    Direct and adaptive cytoprotection

    Dig Dis Sci

    (1986)
  • BH Thomas et al.

    Failure to observe pathology in the rat following chronic dosing with acetaminophen and acetylsalicylic acid

    Res Commun Pathol Pharmacol

    (1972)
  • DJB St. John et al.

    Adaptation of the gastric mucosa to repeated administration of aspirin in the rat

    Am J Dig Dis

    (1973)
  • A Baumgartner et al.

    Indomethacin and turnover of gastric mucosal cells in the rat

    Am J Physiol

    (1986)
  • Cited by (33)

    View all citing articles on Scopus
    1

    S. Levi was supported by the British Digestive Foundation.

    View full text