Abstract | BACKGROUND: AIMS: To assess the effects of tepoxalin on radiation-induced inflammatory damage, and determine its mechanisms of action. METHODS: RESULTS: Irradiated animals had a marked increase in the number of rolling, adherent and emigrated leucocytes in mesenteric venules, and in microvascular permeability. Tepoxalin prevented leucocyte adhesion and the increase in permeability after radiation. Tepoxalin did not inhibit radiation-induced NF-kappaB activation or intercellular adhesion molecule-1 up-regulation, while N-acetyl-L-cysteine, which attenuated NF-kappaB activation, had no effect on leucocyte recruitment. In contrast, tepoxalin inhibited the increase in leukotriene B4 levels after radiation, and the anti-inflammatory effects of the drug were mimicked by zileuton. CONCLUSIONS:
Tepoxalin affords significant protection against radiation-induced inflammation and microvascular dysfunction in splanchnic organs through a mechanism dependent on leukotriene synthesis inhibition.
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Authors | J Panés, M Mollà, M Casadevall, A Salas, M Sans, C Conill, D C Anderson, J Roselló-Catafau, D N Granger, J M Piqué |
Journal | Alimentary pharmacology & therapeutics
(Aliment Pharmacol Ther)
Vol. 14
Issue 6
Pg. 841-50
(Jun 2000)
ISSN: 0269-2813 [Print] England |
PMID | 10848671
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Anti-Inflammatory Agents, Non-Steroidal
- Pyrazoles
- Leukotriene B4
- tepoxalin
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Topics |
- Abdomen
- Animals
- Anti-Inflammatory Agents, Non-Steroidal
(pharmacology)
- Cell Adhesion
- Digestive System
(blood supply)
- Inflammation
- Leukocytes
- Leukotriene B4
(biosynthesis)
- Male
- Permeability
- Pyrazoles
(pharmacology)
- Radiotherapy
(adverse effects)
- Rats
- Rats, Sprague-Dawley
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