Gastric and thymic assay of acute oral treatment of rats with nitric oxide esters of ibuprofen or indomethacin

Downing, J.E.G., Madden, J.C., Ingram, Matthew and Rostron, C. (2005) Gastric and thymic assay of acute oral treatment of rats with nitric oxide esters of ibuprofen or indomethacin Biochemical and Biophysical Research Communications, 334 (2). pp. 646-653. ISSN 1090-2104

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Two common non-steroidal anti-inflammatory drugs (NSAIDs) and their nitric oxide (NO) adducts were evaluated for effects on stomach and thymus. Following 4-h duration (acute) oral dosing of fasted male Wistar rats, 1.33 × 10−4 mol/kg of ibuprofen caused significant visual irritation score and microscopic thinning, although an ulceration assay proved insensitive. Ibuprofen esterified with NO abolished irritation and significantly reduced thinning. Gastro-protective effects of NO-linked ibuprofen were associated with higher levels of diaphorase by optical density, an enzymatic marker of local synthesis of nitric oxide. Both indomethacin and its congener at 2 × 10−5 mol/kg produced microscopic signs of thinning only, not visible irritation or alteration of diaphorase staining. Results suggest that NO-linked ibuprofen can promote resistance to mucosal injury, possibly via local synthesis of NO. All NO-congeners and parent NSAIDs produced comparable reductions in the abundance of medullary nitrergic cells, those synthesising NO in thymus, without significantly lowering T-cellularity, the relative size of cortex wherein T-cells are produced. Findings indicate disturbance of T-cell tolerance, consistent with increased risk of autoimmune susceptibility.

Item Type: Journal article
Uncontrolled Keywords: NO-NSAID; Thymic; Gastric; Toxicity; Diaphorase; NOS
Subjects: C000 Biological and Biomedical Sciences > C700 Molecular Biology, Biophysics and Biochemistry
DOI (a stable link to the resource): 10.1016/j.bbrc.2005.06.149
Faculties: Faculty of Science and Engineering > School of Pharmacy and Biomolecular Sciences > Biomedical Materials
Depositing User: editor spbs
Date Deposited: 08 Nov 2007
Last Modified: 24 Mar 2015 15:08

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