Protective effects of nimesulide (COX inhibitor), AKBA (5-LOX inhibitor), and their combination in aging-associated abnormalities in mice
Protective effects of nimesulide (COX inhibitor), AKBA (5-LOX inhibitor), and their combination in aging-associated abnormalities in mice
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DOI：
10.1358/mf.2005.27.7.920929
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发表时间：
2005-09-01
影响因子：
--
通讯作者：
Kulkarni, SK
中科院分区：
文献类型：
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作者：
Bishnoi, M;Patil, CS;Kulkarni, SK
几种炎症过程在大脑衰老中起着关键作用，并与神经退行性变的易感性增加有关。环氧合酶 - 2（COX - 2）和5 - 脂氧合酶（5 - LOX）是参与花生四烯酸氧化的两种酶，在衰老过程中在中枢神经系统中上调，并与不同的衰老相关脑部病变有关。本实验通过高架十字迷宫实验研究了5 - LOX抑制剂乙酰 - 11 - 酮 - β - 乳香酸（AKBA）、尼美舒利（选择性COX - 2抑制剂）及其组合对年轻和老年小鼠认知能力的影响。连续15天给予AKBA（100 mg/kg，口服）和尼美舒利（2.42 mg/kg，口服）显著逆转了小鼠因衰老导致的记忆保持缺陷。与单独用药相比，AKBA和尼美舒利共同给药提高了老年小鼠的认知能力。AKBA、尼美舒利及其组合逆转了与衰老相关的氧化损伤增加（丙二醛升高，谷胱甘肽降低）。此外，单独使用的COX和LOX抑制剂及其组合未对胃肠道参数产生任何改变；它们还逆转了老年动物因衰老导致的运动功能障碍。基于这些观察结果，目前的研究结果表明，COX和LOX抑制剂（双重抑制剂）的组合可能为治疗与衰老相关的脑部疾病（如阿尔茨海默病）以及不同的运动功能障碍提供一种新的治疗创新，且具有良好的胃肠道耐受性。（c）2005年普罗斯科学出版社。版权所有。
Several inflammatory processes play a critical role in brain aging and are associated with increased vulnerability to neurodegeneration. Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX), two enzymes involved in the oxygenation of the arachidonic acid, are upregulated in the central nervous system during aging and are associated with different aging-related brain pathologies. The present experiment h,as performed to study the effects of 5-LOX inhibitor, acetyl-11-keto-beta-boswellic acid (AKBA), nimesulide (preferential COX-2 inhibitor), and their combination on cognitive performance of young and aged mice, using elevated plus maze test. Chronic administration of AKBA (100 mg/kg, p.o.) and nimesulide (2.42 mg/kg, p.o.) fir 15 days significantly reversed the aging-induced retention deficit in mice. Coadministration of AKBA and nimesulide enhanced the cognitive performance in aged mice when compared with that in per se treatment. The aging-related increase in oxidative damage (increased LPO and decreased GSH) was reversed by AKBA, nimesulide, and their combination. Further, per se COX and LOX inhibitors and their combination did not produce any alteration in gastrointestinal parameters; they also reversed the aging-induced motor dysfunction in the aged animals. Oil the basis of these observations, present findings indicated that the combination of COX and LOX inhibitors (dual inhibitors) pray provide a new, therapeutic innovation for the treatment of aging-related brain disorders such as Alzheimer's disease and different motor dysfunctions with adequate gastrointestinal tolerability. (c) 2005 Prous Science. All rights reserved.