Article date: March 2004
By: Laura Dugo, Stefania Marzocco, Emanuela Mazzon, Rosanna Di Paola, Tiziana Genovese, Achille P Caputi, Salvatore Cuzzocrea in Volume 141, Issue 6, pages 979-987
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 (NOx), 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.
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 (NOx), 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.
British Journal of Pharmacology (2004) 141, 979–987. doi:10.1038/sj.bjp.0705683
DOI: 10.1038/sj.bjp.0705683
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