Wound healing activity of NOE-aspirin: A pre-clinical study
Wound healing activity of NOE-aspirin: A pre-clinical study
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DOI：
10.1016/j.niox.2006.07.004
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发表时间：
2007-02-01
影响因子：
3.9
通讯作者：
Rao, C. Mallikarjuna
中科院分区：
文献类型：
--
作者：
Kaushal, Mandeep;Kutty, N. Gopalan;Rao, C. Mallikarjuna
阿司匹林是最古老的非甾体抗炎药之一，它通过延缓炎症来阻碍组织修复。目前的研究是为了发现硝基氧乙基酯与阿司匹林的连接是否会逆转其治疗抑制剂的倾向。本实验室以阿司匹林为原料，经乙二醇酯化、硝酸和硫酸混合物在0℃下硝化合成阿司匹林硝基氧乙基酯（NOE-Asp）。在切口、死腔和切除三种伤口模型中，评价NOE-Asp对愈合阶段（如胶原、创面收缩和上皮化）和愈合创面疤痕大小的影响。为了评估其对氧化应激的影响，还测定了10日龄肉芽组织中谷胱甘肽（GSH）和硫代巴比妥酸反应物质（TBARS）的水平。进一步筛选NOE-Asp对大鼠足跖水肿模型的抗炎作用。NOE-Asp促进胶原（增加断裂强度、肉芽重量和胶原含量）、伤口收缩和愈合的上皮化阶段。与阿司匹林相比，NOE-Asp在10日龄肉芽组织中也表现出显著的抗氧化作用。结果证实了我们的假设，即阿司匹林与硝基乙基的酯化反应逆转了阿司匹林的抑制愈合作用。该化合物还显示出与阿司匹林同等的抗炎活性。(c) 2006爱思唯尔公司版权所有。
Aspirin, one of the oldest non-steroidal anti-inflammatory drugs, impedes tissue repair by virtue of retarding inflammation. The present study was undertaken to find out if linking of nitrooxyethyl ester to aspirin reverses its healing-depressant propensity. Nitrooxyethyl ester of aspirin (NOE-Asp) was synthesized in our laboratory through well-established synthetic pathway, starting from aspirin through esterification with ethylene glycol and nitration with a mixture of nitric and sulfuric acids at 0 degrees C. The effect of NOE-Asp on phases of healing such as collagenation, wound contraction and epithelialization and on scar size of healed wound was evaluated in three wound models-incision, dead space, and excision wounds. To assess its influence on the oxidative stress, the levels of glutathione (GSH) and thiobarbiturate reactive species (TBARS) were also determined in 10-day-old granulation tissue. NOE-Asp was further screened for its anti-inflammatory activity in rat paw edema model. NOE-Asp promoted collagenation (increase in breaking strength, granulation weight, and collagen content), wound contraction, and epithelialization phases of healing. NOE-Asp also showed a significant antioxidant effect in 10-day-old granulation tissue as compared to aspirin. The results vindicate our assumption that the esterification of aspirin with nirooxyethyl group reverses the healing-suppressant effect of aspirin. The compound also showed equipotent anti-inflammatory activity as aspirin. (c) 2006 Elsevier Inc. All rights reserved.