Comparative protection against rat intestinal reperfusion injury by a new inhibitor of sPLA2, COX-1 and COX-2 selective inhibitors, and an LTC4 receptor antagonist

Arumugam, Thiruma V., Arnold, Naomi, Proctor, Lavinia M., Newman, Michelle, Reid, Robert C., Hansford, Karl A., Fairlie, David P., Shiels, Ian A. and Taylor, Stephen M. (2003) Comparative protection against rat intestinal reperfusion injury by a new inhibitor of sPLA2, COX-1 and COX-2 selective inhibitors, and an LTC4 receptor antagonist. British Journal of Pharmacology, 140 1: 71-80. doi:10.1038/sj.bjp.0705402


Author Arumugam, Thiruma V.
Arnold, Naomi
Proctor, Lavinia M.
Newman, Michelle
Reid, Robert C.
Hansford, Karl A.
Fairlie, David P.
Shiels, Ian A.
Taylor, Stephen M.
Title Comparative protection against rat intestinal reperfusion injury by a new inhibitor of sPLA2, COX-1 and COX-2 selective inhibitors, and an LTC4 receptor antagonist
Formatted title
Comparative protection against rat intestinal reperfusion injury by a new inhibitor of sPLA2, COX-1 and COX-2 selective inhibitors, and an LTC4 receptor antagonist
Journal name British Journal of Pharmacology   Check publisher's open access policy
ISSN 0007-1188
1476-5381
1359-5075
Publication date 2003-09-01
Sub-type Article (original research)
DOI 10.1038/sj.bjp.0705402
Volume 140
Issue 1
Start page 71
End page 80
Total pages 10
Place of publication London, U.K.
Publisher Macmillan
Language eng
Subject C1
730102 Immune system and allergy
320502 Basic Pharmacology
1115 Pharmacology and Pharmaceutical Sciences
Formatted abstract
 A new group IIa sPLA2 inhibitor was compared with selective inhibitors of COX-1, COX-2 and an LTC4 antagonist for effects on local and remote tissue injuries following ischaemia and reperfusion (I/R) of the small intestine in rats.
 
In an acute model of ischaemia (30 min) and reperfusion (150 min) injury in the absence of inhibitors, there was significant intestinal haemorrhage, oedema and mucosal damage, neutropenia, elevated serum levels of aspartate aminotransferase (AST) and hypotension.
 
Preischaemic treatment with the inhibitor of sPLA2 (Group IIa), at 5 mg kg−1 i.v. or 10 mg kg−1 p.o. significantly inhibited I/R-induced neutropenia, the elevation of serum levels of AST, intestinal oedema and hypotension.
 
Pretreatment with the COX-2 inhibitor celebrex (10 mg kg−1 i.v.) and the LTC4 antagonist zafirlukast (1 mg kg−1 i.v.) also showed marked improvement with I/R-induced AST, oedema and neutropenia. Hypotension was only reduced by the LTC4 antagonist. The COX-1 inhibitor flunixin (1 mg kg−1 i.v.) did not effect improvement in the markers of tissue injury.
 
Histological examination of rat I/R injury showed that all of the drugs offered some protection to the mucosal layer damage compared to no drug treatment. Given i.v., the sPLA2 inhibitor was more effective than either the COX-1 or COX-2 inhibitors in preventing rat I/R injury.
 
These results indicate that a potent new inhibitor of sPLA2 (group IIa) protects the rat small intestine from I/R injury after oral or intravenous administration. COX-2 and LTC4 inhibitors also showed some beneficial effects against intestinal I/R injury. Our study suggests that sPLA2 (Group IIa) may have a pathogenic role in intestinal I/R in rats.
© 2010 The British Pharmacological Society

Keyword Pharmacology & Pharmacy
Gut Ischaemia-reperfusion
Spla(2)
Cox-1
Cox-2
Ltc4
Neutropenia
Inflammation
Histopathology
Pharmacokinetics
Mesenteric Ischemia-reperfusion
Platelet-activating-factor
Iia Phospholipase A(2)
Gut Ischemia
Mucosal Damage
Lung Injury
Bacterial Translocation
Organ Failure
Free-radicals
Group-v
Q-Index Code C1
Additional Notes Published Online: 30 Jan 2009

 
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Created: Wed, 15 Aug 2007, 12:02:56 EST