Site-specific lesion formation, inflammation and inducible nitric oxide synthase expression by indomethacin in the rat intestine

Steven M. Evans, F. László, Brendan J R Whittle

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The involvement of nitric oxide (NO) formed by the inducible isoform of NO synthase (iNOS) has been investigated in the development of rat intestinal lesions following indomethacin administration. Over a 72-h period, indomethacin (10 mg kg-1, s.c.) provoked a time-dependent increase in expression of iNOS (assessed by the conversion of radiolabelled l-arginine to citrulline) and enhancement of vascular leakage of radiolabelled human serum albumin in the jejunum which commenced 18 h after indomethacin. Similar effects were not observed in the ileum, colon or caecum. In addition, macroscopic lesions were detectable and myeloperoxidase activity (an index of neutrophil recruitment) were increased in the rat jejunum 18-24 h after indomethacin, but remained at basal levels in the ileum and colon. These findings suggest that indomethacin provokes a site-selective expression of iNOS in the rat jejunum which correlates with lesion formation and vascular leakage, whereas both the ileum and colon are spared. (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)281-285
Number of pages5
JournalEuropean Journal of Pharmacology
Volume388
Issue number3
DOIs
Publication statusPublished - Feb 4 2000

Fingerprint

Nitric Oxide Synthase Type II
Indomethacin
Intestines
Inflammation
Jejunum
Ileum
Protein Isoforms
Colon
Nitric Oxide Synthase
Blood Vessels
Citrulline
Neutrophil Infiltration
Serum Albumin
Peroxidase
Arginine
Nitric Oxide

Keywords

  • Inflammation, intestinal
  • Nitric oxide (NO)
  • Non-steroid anti-inflammatory drug

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Site-specific lesion formation, inflammation and inducible nitric oxide synthase expression by indomethacin in the rat intestine. / Evans, Steven M.; László, F.; Whittle, Brendan J R.

In: European Journal of Pharmacology, Vol. 388, No. 3, 04.02.2000, p. 281-285.

Research output: Contribution to journalArticle

@article{26d1db40af9d4fc3b4229a223f5f9a84,
title = "Site-specific lesion formation, inflammation and inducible nitric oxide synthase expression by indomethacin in the rat intestine",
abstract = "The involvement of nitric oxide (NO) formed by the inducible isoform of NO synthase (iNOS) has been investigated in the development of rat intestinal lesions following indomethacin administration. Over a 72-h period, indomethacin (10 mg kg-1, s.c.) provoked a time-dependent increase in expression of iNOS (assessed by the conversion of radiolabelled l-arginine to citrulline) and enhancement of vascular leakage of radiolabelled human serum albumin in the jejunum which commenced 18 h after indomethacin. Similar effects were not observed in the ileum, colon or caecum. In addition, macroscopic lesions were detectable and myeloperoxidase activity (an index of neutrophil recruitment) were increased in the rat jejunum 18-24 h after indomethacin, but remained at basal levels in the ileum and colon. These findings suggest that indomethacin provokes a site-selective expression of iNOS in the rat jejunum which correlates with lesion formation and vascular leakage, whereas both the ileum and colon are spared. (C) 2000 Elsevier Science B.V.",
keywords = "Inflammation, intestinal, Nitric oxide (NO), Non-steroid anti-inflammatory drug",
author = "Evans, {Steven M.} and F. L{\'a}szl{\'o} and Whittle, {Brendan J R}",
year = "2000",
month = "2",
day = "4",
doi = "10.1016/S0014-2999(99)00869-9",
language = "English",
volume = "388",
pages = "281--285",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",
number = "3",

}

TY - JOUR

T1 - Site-specific lesion formation, inflammation and inducible nitric oxide synthase expression by indomethacin in the rat intestine

AU - Evans, Steven M.

AU - László, F.

AU - Whittle, Brendan J R

PY - 2000/2/4

Y1 - 2000/2/4

N2 - The involvement of nitric oxide (NO) formed by the inducible isoform of NO synthase (iNOS) has been investigated in the development of rat intestinal lesions following indomethacin administration. Over a 72-h period, indomethacin (10 mg kg-1, s.c.) provoked a time-dependent increase in expression of iNOS (assessed by the conversion of radiolabelled l-arginine to citrulline) and enhancement of vascular leakage of radiolabelled human serum albumin in the jejunum which commenced 18 h after indomethacin. Similar effects were not observed in the ileum, colon or caecum. In addition, macroscopic lesions were detectable and myeloperoxidase activity (an index of neutrophil recruitment) were increased in the rat jejunum 18-24 h after indomethacin, but remained at basal levels in the ileum and colon. These findings suggest that indomethacin provokes a site-selective expression of iNOS in the rat jejunum which correlates with lesion formation and vascular leakage, whereas both the ileum and colon are spared. (C) 2000 Elsevier Science B.V.

AB - The involvement of nitric oxide (NO) formed by the inducible isoform of NO synthase (iNOS) has been investigated in the development of rat intestinal lesions following indomethacin administration. Over a 72-h period, indomethacin (10 mg kg-1, s.c.) provoked a time-dependent increase in expression of iNOS (assessed by the conversion of radiolabelled l-arginine to citrulline) and enhancement of vascular leakage of radiolabelled human serum albumin in the jejunum which commenced 18 h after indomethacin. Similar effects were not observed in the ileum, colon or caecum. In addition, macroscopic lesions were detectable and myeloperoxidase activity (an index of neutrophil recruitment) were increased in the rat jejunum 18-24 h after indomethacin, but remained at basal levels in the ileum and colon. These findings suggest that indomethacin provokes a site-selective expression of iNOS in the rat jejunum which correlates with lesion formation and vascular leakage, whereas both the ileum and colon are spared. (C) 2000 Elsevier Science B.V.

KW - Inflammation, intestinal

KW - Nitric oxide (NO)

KW - Non-steroid anti-inflammatory drug

UR - http://www.scopus.com/inward/record.url?scp=0342546047&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0342546047&partnerID=8YFLogxK

U2 - 10.1016/S0014-2999(99)00869-9

DO - 10.1016/S0014-2999(99)00869-9

M3 - Article

C2 - 10675738

AN - SCOPUS:0342546047

VL - 388

SP - 281

EP - 285

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

IS - 3

ER -