Gastric and thymic assay of acute oral treatment of rats with nitric oxide esters of ibuprofen or indomethacin
Gastric and thymic assay of acute oral treatment of rats with nitric oxide esters of ibuprofen or indomethacin
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DOI：
10.1016/j.bbrc.2005.06.149
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发表时间：
2005-08-26
影响因子：
3.1
通讯作者：
Rostron, C
中科院分区：
文献类型：
--
作者：
Downing, JEG;Madden, JC;Rostron, C
评价了两种常用的非甾体抗炎药（NSAIDs）及其一氧化氮（NO）加合物对布洛芬mol/kg引起的胃和胸腺的影响。禁食雄性Wistar大鼠经口给药4小时（急性）后，1.33 x 10（-4）显著视觉刺激评分和显微镜下变薄，尽管溃疡试验证明不敏感。酯化NO的Iceland消除了刺激，并显着减少变薄。NO-连接布洛芬的胃保护作用与更高水平的黄递酶相关，黄递酶是局部一氧化氮合成的酶标记物。吲哚美辛及其同类物在2 × 10（-5）mol/kg时仅产生变薄的显微镜体征，无可见刺激或心肌黄酶染色改变。结果表明，NO-连接布洛芬可以促进抵抗粘膜损伤，可能是通过本地合成NO。所有NO-同系物和母体NSAID产生的髓质氮能细胞的丰度相当的减少，在胸腺中合成NO，而不显着降低T-细胞，皮质的相对大小，其中T-细胞产生。结果表明T细胞耐受性紊乱，与自身免疫易感性风险增加一致。(c)2005年爱思唯尔公司All rights reserved.
Two common non-steroidal anti-inflammatory drugs (NSAIDs) and their nitric oxide (NO) adducts were evaluated for effects on mol/kg of ibuprofen caused stomach and thymus. Following 4-h duration (acute) oral dosing of fasted male Wistar rats, 1.33 x 10(-4) 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. (c) 2005 Elsevier Inc. All rights reserved.