Gastric and thymic assay of acute oral treatment of rats with nitric oxide esters of ibuprofen or indomethacin |
| |
Authors: | Downing James E G Madden Judith C Ingram Matthew J Rostron Christopher |
| |
Institution: | School of Pharmacy and Chemistry, Liverpool John Moores University, Byrom St., Liverpool L3 3AF, UK. jdowning@livjm.ac.uk |
| |
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. |
| |
Keywords: | NO-NSAID Thymic Gastric Toxicity Diaphorase NOS |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|