Abstract:
: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 x 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 x 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.
journal_name
Biochem Biophys Res Communjournal_title
Biochemical and biophysical research communicationsauthors
Downing JE,Madden JC,Ingram MJ,Rostron Cdoi
10.1016/j.bbrc.2005.06.149subject
Has Abstractpub_date
2005-08-26 00:00:00pages
646-53issue
2eissn
0006-291Xissn
1090-2104pii
S0006-291X(05)01384-7journal_volume
334pub_type
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