Ibuprofen or piroxicam protects nigral neurons and delays the development of L-dopa induced dyskinesia in rats with experimental Parkinsonism: Influence on angiogenesis (Retracted Article)
Ibuprofen or piroxicam protects nigral neurons and delays the development of L-dopa induced dyskinesia in rats with experimental Parkinsonism: Influence on angiogenesis (Retracted Article)
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DOI：
10.1016/j.neuropharm.2016.03.034
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发表时间：
2016-08-01
影响因子：
4.7
通讯作者：
Moustafa, Yasser M.
中科院分区：
文献类型：
--
作者：
Teema, Asmaa M.;Zaitone, Sawsan A.;Moustafa, Yasser M.
神经炎症和血管生成与帕金森病（PD）的发病有关。本研究探讨了布洛芬或吡洛昔康对帕金森大鼠左旋多巴运动反应和运动障碍的影响，重点研究了这两种非甾体抗炎药（NSAIDs）的抗血管生成作用。将大鼠分为9组：ⅰ组：载药组，ⅱ组：鱼藤酮组，大鼠注射9次鱼藤酮（1 mg/kg/48 h），ⅲ、ⅳ组：鱼藤酮+布洛芬（10或30 mg/kg），ⅴ、ⅵ组：鱼藤酮+吡罗西康（1或3 mg/kg），ⅶ组：鱼藤酮+左旋多巴/卡比多巴+布洛芬（100/10 mg/kg）， VIII-IX组：鱼藤酮+左旋多巴/卡比多巴+布洛芬（30 mg/kg）或吡罗西康（3 mg/kg）。一般情况下，每天给药10周。鱼藤酮处理大鼠运动功能障碍，纹状体多巴胺水平降低，黑质酪氨酸羟化酶染色水平降低，纹状体环氧化酶-2 （COX-2）和血管内皮生长因子（VEGF）水平升高（P < 0.05）。左旋多巴治疗在实验过程中表现出逐渐消退，以及异常的不自主运动和纹状体VEGF水平上调。布洛芬或吡罗西康联合左旋多巴在第10周末保留左旋多巴的作用，延缓运动障碍的发展，降低纹状体COX-2和VEGF水平。总之，目前的研究表明，布洛芬和吡罗西康是PD患者神经保护的有希望的候选者，可能与左旋多巴联合使用，以确保其作用的持久性，并延缓运动障碍的发展。(C) 2016 Elsevier Ltd.版权所有。
Neuroinflammation and angiogenesis have been involved in the pathogenesis of Parkinson's disease (PD). This study investigated the effect of ibuprofen or piroxicam on the motor response to L-dopa and development of dyskinesia in Parkinsonian rats focusing on the anti-angiogenic role of the two non steroidal anti-inflammatory drugs (NSAIDs). Rats were divided into nine groups as follows: Group I: the vehicle group, Group II: rotenone group, rats were injected with nine doses of rotenone (1 mg/kg/48 h), group III&IV: rats received rotenone + ibuprofen (10 or 30 mg/kg), Group V-VI: rats received rotenone + piroxicam (1 or 3 mg/kg), Group VII: rats received rotenone + L-dopa/carbidopa (100/10 mg/kg), Group VIII-IX: rats received rotenone + L-dopa/carbidopa + ibuprofen (30 mg/kg) or piroxicam (3 mg/kg). In general, drugs were administered daily for ten weeks. Rotenone-treated rats showed motor dysfunction, lower striatal dopamine, lower staining for nigral tyrosine hydroxylase but higher level of striatal cydooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) compared to vehicle-treated rats (P < 0.05). Treatment with L-dopa showed wearing-off over the course of the experiment in addition to development of abnormal involuntary movements and upregulated striatal VEGF level. Treatment with ibuprofen or piroxicam in combination with L-dopa preserved the effect of L-dopa at the end of week 10, delayed the development of dyskinesia and decreased striatal COX-2 and VEGF levels. In conclusion, the current study suggests that ibuprofen and piroxicam are promising candidates for neuroprotection in PD and may have utility in conjunction with L-dopa in order to ensure the longevity of its action and to delay the development of dyskinesia. (C) 2016 Elsevier Ltd. All rights reserved.