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

Content Provider	PubMed Central
Author	Dugo, Laura Marzocco, Stefania Mazzon, Emanuela Paola, Rosanna Di Genovese, Tiziana Caputi, Achille P. Salvatore, Cuzzocrea
Copyright Year	2004
Abstract	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. 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). 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). 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. 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. 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.
Related Links	http://dx.doi.org/10.1038/sj.bjp.0705683
Ending Page	987
Page Count	9
Starting Page	979
File Format	PDF
ISSN	00071188
Journal	British Journal of Pharmacology
Issue Number	6
Volume Number	141
Language	English
Publisher Date	2004-03-01
Access Restriction	Open
Subject Keyword	Pharmacology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Pharmacology

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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