Effects of GW274150, a novel and selective inhibitor of iNOS activity, in acute lung inflammation

Laura Dugo, Stefania Marzocco, Emanuela Mazzon, Rosanna Di Paola, Tiziana Genovese, Achille P. Caputi, Salvatore Cuzzocrea

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

1. The aim of this study was to investigate the effect of GW274150, a novel, potent and selective inhibitor of inducible nitric oxide synthase (iNOS) activity in a model of lung injury induced by carrageenan administration in the rats. 2. Injection of carrageenan into the pleural cavity of rats elicited an acute inflammatory response characterized by: fluid accumulation in the pleural cavity which contained a large number of polymorphonuclear cells (PMNs) as well as an infiltration of PMNs in lung tissues and subsequent lipid peroxidation, and increased production of nitrite/nitrate (NO x), tumour necrosis factor α (TNF-α) and interleukin-1β (IL-1β). 3. All parameters of inflammation were attenuated in a dose-dependent manner by GW274150 (2.5, 5 and 10 mg kg -1 injected i.p. 5 min before carrageenan). 4. Carrageenan induced an upregulation of the intracellular adhesion molecules-1 (ICAM-1), as well as nitrotyrosine and poly (ADP-ribose) (PAR) as determined by immunohistochemical analysis of lung tissues. 5. The degree of staining for the ICAM-1, nitrotyrosine and PAR was reduced by GW274150. These results clearly confirm that NO from iNOS plays a role in the development of the inflammatory response by altering key components of the inflammatory cascade. 6. GW274150 may offer a novel therapeutic approach for the management of various inflammatory diseases where NO and related radicals have been postulated to play a role.

Original languageEnglish
Pages (from-to)979-987
Number of pages9
JournalBritish Journal of Pharmacology
Volume141
Issue number6
DOIs
Publication statusPublished - Mar 2004

Fingerprint

Carrageenan
Nitric Oxide Synthase Type II
Pneumonia
Pleural Cavity
Poly Adenosine Diphosphate Ribose
Lung
Lung Injury
Nitrites
Interleukin-1
Nitrates
Lipid Peroxidation
Up-Regulation
Tumor Necrosis Factor-alpha
Cell Count
Staining and Labeling
Inflammation
Injections
GW 274150
3-nitrotyrosine
Therapeutics

Keywords

  • Adhesion molecules
  • Inflammation
  • iNOS
  • Peroxynitrite
  • Pleurisy
  • Rat
  • Reactive oxygen species

ASJC Scopus subject areas

  • Pharmacology

Cite this

Effects of GW274150, a novel and selective inhibitor of iNOS activity, in acute lung inflammation. / Dugo, Laura; Marzocco, Stefania; Mazzon, Emanuela; Di Paola, Rosanna; Genovese, Tiziana; Caputi, Achille P.; Cuzzocrea, Salvatore.

In: British Journal of Pharmacology, Vol. 141, No. 6, 03.2004, p. 979-987.

Research output: Contribution to journalArticle

Dugo, Laura ; Marzocco, Stefania ; Mazzon, Emanuela ; Di Paola, Rosanna ; Genovese, Tiziana ; Caputi, Achille P. ; Cuzzocrea, Salvatore. / Effects of GW274150, a novel and selective inhibitor of iNOS activity, in acute lung inflammation. In: British Journal of Pharmacology. 2004 ; Vol. 141, No. 6. pp. 979-987.
@article{51b83985d42a4351abca238daa6f638f,
title = "Effects of GW274150, a novel and selective inhibitor of iNOS activity, in acute lung inflammation",
abstract = "1. The aim of this study was to investigate the effect of GW274150, a novel, potent and selective inhibitor of inducible nitric oxide synthase (iNOS) activity in a model of lung injury induced by carrageenan administration in the rats. 2. Injection of carrageenan into the pleural cavity of rats elicited an acute inflammatory response characterized by: fluid accumulation in the pleural cavity which contained a large number of polymorphonuclear cells (PMNs) as well as an infiltration of PMNs in lung tissues and subsequent lipid peroxidation, and increased production of nitrite/nitrate (NO x), tumour necrosis factor α (TNF-α) and interleukin-1β (IL-1β). 3. All parameters of inflammation were attenuated in a dose-dependent manner by GW274150 (2.5, 5 and 10 mg kg -1 injected i.p. 5 min before carrageenan). 4. Carrageenan induced an upregulation of the intracellular adhesion molecules-1 (ICAM-1), as well as nitrotyrosine and poly (ADP-ribose) (PAR) as determined by immunohistochemical analysis of lung tissues. 5. The degree of staining for the ICAM-1, nitrotyrosine and PAR was reduced by GW274150. These results clearly confirm that NO from iNOS plays a role in the development of the inflammatory response by altering key components of the inflammatory cascade. 6. GW274150 may offer a novel therapeutic approach for the management of various inflammatory diseases where NO and related radicals have been postulated to play a role.",
keywords = "Adhesion molecules, Inflammation, iNOS, Peroxynitrite, Pleurisy, Rat, Reactive oxygen species",
author = "Laura Dugo and Stefania Marzocco and Emanuela Mazzon and {Di Paola}, Rosanna and Tiziana Genovese and Caputi, {Achille P.} and Salvatore Cuzzocrea",
year = "2004",
month = "3",
doi = "10.1038/sj.bjp.0705683",
language = "English",
volume = "141",
pages = "979--987",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
publisher = "Wiley-Blackwell",
number = "6",

}

TY - JOUR

T1 - Effects of GW274150, a novel and selective inhibitor of iNOS activity, in acute lung inflammation

AU - Dugo, Laura

AU - Marzocco, Stefania

AU - Mazzon, Emanuela

AU - Di Paola, Rosanna

AU - Genovese, Tiziana

AU - Caputi, Achille P.

AU - Cuzzocrea, Salvatore

PY - 2004/3

Y1 - 2004/3

N2 - 1. The aim of this study was to investigate the effect of GW274150, a novel, potent and selective inhibitor of inducible nitric oxide synthase (iNOS) activity in a model of lung injury induced by carrageenan administration in the rats. 2. Injection of carrageenan into the pleural cavity of rats elicited an acute inflammatory response characterized by: fluid accumulation in the pleural cavity which contained a large number of polymorphonuclear cells (PMNs) as well as an infiltration of PMNs in lung tissues and subsequent lipid peroxidation, and increased production of nitrite/nitrate (NO x), tumour necrosis factor α (TNF-α) and interleukin-1β (IL-1β). 3. All parameters of inflammation were attenuated in a dose-dependent manner by GW274150 (2.5, 5 and 10 mg kg -1 injected i.p. 5 min before carrageenan). 4. Carrageenan induced an upregulation of the intracellular adhesion molecules-1 (ICAM-1), as well as nitrotyrosine and poly (ADP-ribose) (PAR) as determined by immunohistochemical analysis of lung tissues. 5. The degree of staining for the ICAM-1, nitrotyrosine and PAR was reduced by GW274150. These results clearly confirm that NO from iNOS plays a role in the development of the inflammatory response by altering key components of the inflammatory cascade. 6. GW274150 may offer a novel therapeutic approach for the management of various inflammatory diseases where NO and related radicals have been postulated to play a role.

AB - 1. The aim of this study was to investigate the effect of GW274150, a novel, potent and selective inhibitor of inducible nitric oxide synthase (iNOS) activity in a model of lung injury induced by carrageenan administration in the rats. 2. Injection of carrageenan into the pleural cavity of rats elicited an acute inflammatory response characterized by: fluid accumulation in the pleural cavity which contained a large number of polymorphonuclear cells (PMNs) as well as an infiltration of PMNs in lung tissues and subsequent lipid peroxidation, and increased production of nitrite/nitrate (NO x), tumour necrosis factor α (TNF-α) and interleukin-1β (IL-1β). 3. All parameters of inflammation were attenuated in a dose-dependent manner by GW274150 (2.5, 5 and 10 mg kg -1 injected i.p. 5 min before carrageenan). 4. Carrageenan induced an upregulation of the intracellular adhesion molecules-1 (ICAM-1), as well as nitrotyrosine and poly (ADP-ribose) (PAR) as determined by immunohistochemical analysis of lung tissues. 5. The degree of staining for the ICAM-1, nitrotyrosine and PAR was reduced by GW274150. These results clearly confirm that NO from iNOS plays a role in the development of the inflammatory response by altering key components of the inflammatory cascade. 6. GW274150 may offer a novel therapeutic approach for the management of various inflammatory diseases where NO and related radicals have been postulated to play a role.

KW - Adhesion molecules

KW - Inflammation

KW - iNOS

KW - Peroxynitrite

KW - Pleurisy

KW - Rat

KW - Reactive oxygen species

UR - http://www.scopus.com/inward/record.url?scp=1942472504&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1942472504&partnerID=8YFLogxK

U2 - 10.1038/sj.bjp.0705683

DO - 10.1038/sj.bjp.0705683

M3 - Article

C2 - 14769784

AN - SCOPUS:1942472504

VL - 141

SP - 979

EP - 987

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 6

ER -