Effect of cyclooxygenase-2 inhibition on human Helicobacter pylori gastritis

Mechanisms underlying gastrointestinal safety and implications for cancer chemoprevention

J. M. Scheiman, J. K. Greenson, J. Lee, B. Cryer

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Cyclooxygenase (COX)-2 expression and prostaglandin production is increased by Helicobacter pylori infection. Non-selective COX inhibitors reduce prostaglandins and mucosal proliferation in infected mucosa and may reduce gastric cancer risk, but ulceration precludes their use. COX-2 inhibitors cause fewer ulcers and may be chemopreventive. Physiological studies of COX-2 inhibitors in humans with H. pylori infection have not been performed. Aim: To study the impact of COX-2 specific inhibition on gastric prostaglandin levels, H. pylori gastritis and proliferation. Methods: Twenty infected (eight males, 12 females; age 38 ± 1.8) and six uninfected (four males, two females; age 36 ± 3.5) healthy volunteers received rofecoxib 25 mg daily for 14 days. Endoscopic biopsies were evaluated for prostaglandin E2 (PGE2) content, gastritis and proliferation. Results: Before drug therapy, compared to uninfected, H. pylori-infected subjects had significantly higher: (a) gastric mucosal PGE2 (pg/mg tissue) in the gastric body and antrum, (b) H. pylori score in body and antrum and (c) mid-gland proliferation index in antrum and body. The COX-2 inhibitor did not significantly affect PGE2 levels, gastritis scores or proliferation indices in the body or antrum in the H. pylori-positive or -negative subjects. Conclusion: The predominant source of increased gastric PGE2 in H. pylori infection appears to be COX-1-derived. In non-ulcerated H. pylori gastritis, COX-2 inhibition does not affect cellular proliferation. Rofecoxib's lack of effect on gastric prostaglandin levels and proliferation in H. pylori-infected mucosa may explain the absence of an increased ulcer risk among COX-2 inhibitor users with H. pylori infection. The lack of significant effect on intermediate biomarkers raises uncertainty regarding the potential of specific COX-2 inhibitors for chemoprevention of gastric cancer.

Original languageEnglish (US)
Pages (from-to)1535-1543
Number of pages9
JournalAlimentary Pharmacology and Therapeutics
Volume17
Issue number12
DOIs
StatePublished - Jun 15 2003

Fingerprint

Chemoprevention
Gastritis
Cyclooxygenase 2
Helicobacter pylori
Safety
Cyclooxygenase 2 Inhibitors
Helicobacter Infections
Dinoprostone
Neoplasms
Stomach
Prostaglandins
Ulcer
Stomach Neoplasms
Mucous Membrane
Prostaglandins H
Pyloric Antrum
Cyclooxygenase 1
Cyclooxygenase Inhibitors
Pylorus
Uncertainty

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

@article{0a920914ba2e4900aacdb7dbcc929c09,
title = "Effect of cyclooxygenase-2 inhibition on human Helicobacter pylori gastritis: Mechanisms underlying gastrointestinal safety and implications for cancer chemoprevention",
abstract = "Cyclooxygenase (COX)-2 expression and prostaglandin production is increased by Helicobacter pylori infection. Non-selective COX inhibitors reduce prostaglandins and mucosal proliferation in infected mucosa and may reduce gastric cancer risk, but ulceration precludes their use. COX-2 inhibitors cause fewer ulcers and may be chemopreventive. Physiological studies of COX-2 inhibitors in humans with H. pylori infection have not been performed. Aim: To study the impact of COX-2 specific inhibition on gastric prostaglandin levels, H. pylori gastritis and proliferation. Methods: Twenty infected (eight males, 12 females; age 38 ± 1.8) and six uninfected (four males, two females; age 36 ± 3.5) healthy volunteers received rofecoxib 25 mg daily for 14 days. Endoscopic biopsies were evaluated for prostaglandin E2 (PGE2) content, gastritis and proliferation. Results: Before drug therapy, compared to uninfected, H. pylori-infected subjects had significantly higher: (a) gastric mucosal PGE2 (pg/mg tissue) in the gastric body and antrum, (b) H. pylori score in body and antrum and (c) mid-gland proliferation index in antrum and body. The COX-2 inhibitor did not significantly affect PGE2 levels, gastritis scores or proliferation indices in the body or antrum in the H. pylori-positive or -negative subjects. Conclusion: The predominant source of increased gastric PGE2 in H. pylori infection appears to be COX-1-derived. In non-ulcerated H. pylori gastritis, COX-2 inhibition does not affect cellular proliferation. Rofecoxib's lack of effect on gastric prostaglandin levels and proliferation in H. pylori-infected mucosa may explain the absence of an increased ulcer risk among COX-2 inhibitor users with H. pylori infection. The lack of significant effect on intermediate biomarkers raises uncertainty regarding the potential of specific COX-2 inhibitors for chemoprevention of gastric cancer.",
author = "Scheiman, {J. M.} and Greenson, {J. K.} and J. Lee and B. Cryer",
year = "2003",
month = "6",
day = "15",
doi = "10.1046/j.1365-2036.2003.01587.x",
language = "English (US)",
volume = "17",
pages = "1535--1543",
journal = "Alimentary Pharmacology and Therapeutics",
issn = "0269-2813",
publisher = "Wiley-Blackwell",
number = "12",

}

TY - JOUR

T1 - Effect of cyclooxygenase-2 inhibition on human Helicobacter pylori gastritis

T2 - Mechanisms underlying gastrointestinal safety and implications for cancer chemoprevention

AU - Scheiman, J. M.

AU - Greenson, J. K.

AU - Lee, J.

AU - Cryer, B.

PY - 2003/6/15

Y1 - 2003/6/15

N2 - Cyclooxygenase (COX)-2 expression and prostaglandin production is increased by Helicobacter pylori infection. Non-selective COX inhibitors reduce prostaglandins and mucosal proliferation in infected mucosa and may reduce gastric cancer risk, but ulceration precludes their use. COX-2 inhibitors cause fewer ulcers and may be chemopreventive. Physiological studies of COX-2 inhibitors in humans with H. pylori infection have not been performed. Aim: To study the impact of COX-2 specific inhibition on gastric prostaglandin levels, H. pylori gastritis and proliferation. Methods: Twenty infected (eight males, 12 females; age 38 ± 1.8) and six uninfected (four males, two females; age 36 ± 3.5) healthy volunteers received rofecoxib 25 mg daily for 14 days. Endoscopic biopsies were evaluated for prostaglandin E2 (PGE2) content, gastritis and proliferation. Results: Before drug therapy, compared to uninfected, H. pylori-infected subjects had significantly higher: (a) gastric mucosal PGE2 (pg/mg tissue) in the gastric body and antrum, (b) H. pylori score in body and antrum and (c) mid-gland proliferation index in antrum and body. The COX-2 inhibitor did not significantly affect PGE2 levels, gastritis scores or proliferation indices in the body or antrum in the H. pylori-positive or -negative subjects. Conclusion: The predominant source of increased gastric PGE2 in H. pylori infection appears to be COX-1-derived. In non-ulcerated H. pylori gastritis, COX-2 inhibition does not affect cellular proliferation. Rofecoxib's lack of effect on gastric prostaglandin levels and proliferation in H. pylori-infected mucosa may explain the absence of an increased ulcer risk among COX-2 inhibitor users with H. pylori infection. The lack of significant effect on intermediate biomarkers raises uncertainty regarding the potential of specific COX-2 inhibitors for chemoprevention of gastric cancer.

AB - Cyclooxygenase (COX)-2 expression and prostaglandin production is increased by Helicobacter pylori infection. Non-selective COX inhibitors reduce prostaglandins and mucosal proliferation in infected mucosa and may reduce gastric cancer risk, but ulceration precludes their use. COX-2 inhibitors cause fewer ulcers and may be chemopreventive. Physiological studies of COX-2 inhibitors in humans with H. pylori infection have not been performed. Aim: To study the impact of COX-2 specific inhibition on gastric prostaglandin levels, H. pylori gastritis and proliferation. Methods: Twenty infected (eight males, 12 females; age 38 ± 1.8) and six uninfected (four males, two females; age 36 ± 3.5) healthy volunteers received rofecoxib 25 mg daily for 14 days. Endoscopic biopsies were evaluated for prostaglandin E2 (PGE2) content, gastritis and proliferation. Results: Before drug therapy, compared to uninfected, H. pylori-infected subjects had significantly higher: (a) gastric mucosal PGE2 (pg/mg tissue) in the gastric body and antrum, (b) H. pylori score in body and antrum and (c) mid-gland proliferation index in antrum and body. The COX-2 inhibitor did not significantly affect PGE2 levels, gastritis scores or proliferation indices in the body or antrum in the H. pylori-positive or -negative subjects. Conclusion: The predominant source of increased gastric PGE2 in H. pylori infection appears to be COX-1-derived. In non-ulcerated H. pylori gastritis, COX-2 inhibition does not affect cellular proliferation. Rofecoxib's lack of effect on gastric prostaglandin levels and proliferation in H. pylori-infected mucosa may explain the absence of an increased ulcer risk among COX-2 inhibitor users with H. pylori infection. The lack of significant effect on intermediate biomarkers raises uncertainty regarding the potential of specific COX-2 inhibitors for chemoprevention of gastric cancer.

UR - http://www.scopus.com/inward/record.url?scp=0038574389&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0038574389&partnerID=8YFLogxK

U2 - 10.1046/j.1365-2036.2003.01587.x

DO - 10.1046/j.1365-2036.2003.01587.x

M3 - Article

VL - 17

SP - 1535

EP - 1543

JO - Alimentary Pharmacology and Therapeutics

JF - Alimentary Pharmacology and Therapeutics

SN - 0269-2813

IS - 12

ER -