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Endothelial changes precede mucosal ulceration induced by indomethacin: an experimental study in the rat

Kelly, D; Anthony, A; Piasecki, C; Lewin, J; Pounder, RE; Wakefield, AJ; (2000) Endothelial changes precede mucosal ulceration induced by indomethacin: an experimental study in the rat. Alimentary Pharmacology and Therapeutics , 14 (4) 489 - 496.

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Abstract

BACKGROUND: Indomethacin has been shown to damage the villous microvasculature concomitant with alterations in villous blood flow in the rat. AIM: To test the hypothesis that alterations in blood flow result from ultrastructural damage to microvasculature endothelium. METHODS: In anaesthetized rats, jejunal villi were exteriorized in a chamber and blood flow in surface capillaries visualized by fluorescence microscopy. Villi were exposed both luminally and systemically to indomethacin (100 microg/mL) for 10 min or until blood slowing or stasis had occurred in superficial capillaries (n=3 per group). Control animals received both a luminal and intravenous vehicle for 45 min (n=3). The small intestines were vascular perfusion-fixed with 1.5% glutaraldehyde and studied by transmission electron microscopy. RESULTS: All controls appeared to be ultrastructurally normal. A 10 min exposure to indomethacin had no effect upon the epithelium but resulted in mild endothelial vacuolization and the development of small finger-like projections into the lumen of villus surface microvasculature. At the point of blood slowing, villus tip epithelium was again normal but the endothelial vacuolization and finger-like projections became more obvious. The endothelial projections and vacuolization became severe at the point of blood stasis; this also coincided with epithelial degeneration. CONCLUSION: This study shows that villus surface microvasculature is the earliest site of morphological damage after indomethacin exposure

Type:Article
Title:Endothelial changes precede mucosal ulceration induced by indomethacin: an experimental study in the rat
Additional information:UI - 20223007 LA - eng RN - 0 (Anti-Inflammatory Agents, Non-Steroidal) RN - 53-86-1 (Indomethacin) PT - Journal Article DA - 20000511 IS - 0269-2813 SB - IM CY - ENGLAND JC - A5D
Keywords:0 (Anti-Inflammatory Agents, Non-Steroidal), 53-86-1 (Indomethacin), Anti-Inflammatory Agents, Non-Steroidal, Capillaries, chemically induced, control, Damage, development, drug effects, Electron, electron microscopy, Endothelial, Endothelium, Vascular, epithelial, Epithelium, experimental, Fluorescence, Indomethacin, intestine, Mucosal, pathology, rat, rats, small intestine, Stomach Ulcer, toxicity, transmission, Ulceration, Ultrastructural, vascular
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of)

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