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

J.E.G. Downing, J.C. Madden, Matthew Ingram, C. Rostron

Research output: Contribution to journalArticle

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 × 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.
Original languageEnglish
Pages (from-to)646-653
Number of pages8
JournalBiochemical and biophysical research communications
Volume334
Issue number2
Publication statusPublished - Aug 2005

Keywords

  • NO-NSAID
  • Thymic
  • Gastric
  • Toxicity
  • Diaphorase
  • NOS

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