Relationship between PAF-acether and thromboxane A2 biosynthesis in endotoxin-induced intestinal damage in the rat

Prostaglandins
N K Boughton-SmithB J Whittle

Abstract

PAF-receptor antagonists are known to inhibit gastrointestinal damage induced by endotoxin. In the present study, the interaction between the biosynthesis of PAF and thromboxane (TX) A2, as putative mediators of the acute intestinal damage induced by endotoxin, has been investigated in the anaesthetised rat. Bolus intravenous administration of lipopolysaccharide from E. coli (5-50 mg/kg) induced dose-related jejunal damage, assessed using both macroscopic and histological techniques. This damage was accompanied by significant increases in the jejunal formation of PAF determined by bioassay, and of TXB2, determined by radioimmunoassay. Pretreatment with the structurally-unrelated thromboxane synthase inhibitors, 1-benzyl imidazole (10-50 mg/kg) or OKY 1581 (25 mg/kg) substantially reduced both jejunal damage and TXB2 formation, but did not inhibit PAF formation. Likewise, pretreatment with indomethacin (5 mg/kg) or BW 755C (50 mg/kg) reduced jejunal damage and TXB2 formation but did not affect PAF formation. Pretreatment (2h) with dexamethasone (4 mg/kg) reduced jejunal damage and the formation of both TXB2 and PAF. Intravenous infusion of PAF (100 ng/kg/min for 10 min) induced jejunal damage and significantly increased the form...Continue Reading

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Citations

Jan 1, 1992·Agents and Actions·N K Boughton-SmithB J Whittle
Dec 4, 1990·European Journal of Pharmacology·N K Boughton-SmithS Moncada
Jun 23, 1995·European Journal of Pharmacology·J L WallaceS N Elliott
Feb 26, 2000·European Journal of Clinical Investigation·A A VrijR W Stockbrügger
Dec 1, 1990·British Journal of Pharmacology·I R HutchesonN K Boughton-Smith
Nov 1, 1993·British Journal of Pharmacology·N K Boughton-SmithS Moncada
Jun 1, 1995·British Journal of Pharmacology·F LászlóS Moncada
Jan 1, 1992·Annals of the New York Academy of Sciences·B J WhittleS Moncada
Feb 27, 2008·Journal of Clinical Biochemistry and Nutrition·Yuji NaitoToshikazu Yoshikawa
Jul 12, 2014·The Journal of Surgical Research·Katharina Effenberger-NeidnichtHerbert de Groot
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Apr 6, 2004·Gastrointestinal Endoscopy Clinics of North America·Robynne Chutkan, Nabil Toubia
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Dec 18, 2001·Experimental Biology and Medicine·J L Wallace, L Ma

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