Ursodeoxycholic Acid Ameliorates Apoptotic Cascade in the Rotenone Model of Parkinson's Disease: Modulation of Mitochondrial Perturbations
Ursodeoxycholic Acid Ameliorates Apoptotic Cascade in the Rotenone Model of Parkinson's Disease: Modulation of Mitochondrial Perturbations
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DOI：
10.1007/s12035-014-9043-8
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发表时间：
2016-03-01
影响因子：
5.1
通讯作者：
Salem, Hesham A.
中科院分区：
文献类型：
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作者：
Abdelkader, Noha F.;Safar, Marwa M.;Salem, Hesham A.
最近出现的熊去氧胆酸（UDCA）作为一种竞争者，在修改人多巴胺能细胞的神经毒性，以及其公认的抗凋亡和抗炎潜力，在各种肝脏病理提高了动力，在大鼠鱼藤酮模型中研究其抗帕金森病的作用。UDCA显著改善了旷场试验中的运动表现，并阻止了纹状体多巴胺含量的下降。同时，它改善了线粒体功能，如电子显微镜检查所示，ATP升高与线粒体完整性的保护相关。此外，通过其抗炎潜力，UDCA降低了鱼藤酮诱导的核因子-κ B表达和肿瘤坏死因子α水平。此外，UDCA修正Bax和Bcl-2的改变，降低caspase-8、caspase-9和caspase-3的活性，表明其通过调节内源性和外源性途径抑制鱼藤酮诱导的细胞凋亡。总之，UDCA可以作为一种新的方法，通过抗凋亡和抗炎机制治疗帕金森病。这些影响可能与多巴胺合成和线粒体调节有关。
The recent emergence of ursodeoxycholic acid (UDCA) as a contender in modifying neurotoxicity in human dopaminergic cells as well as its recognized anti-apoptotic and anti-inflammatory potentials in various hepatic pathologies raised impetus in investigating its anti-parkinsonian effect in rat rotenone model. UDCA prominently improved motor performance in the open field test and halted the decline in the striatal dopamine content. Meanwhile, it improved mitochondrial function as verified by elevation of ATP associated with preservation of mitochondrial integrity as portrayed in the electron microscope examination. In addition, through its anti-inflammatory potential, UDCA reduced the rotenone-induced nuclear factor-kappa B expression and tumor necrosis factor alpha level. Furthermore, UDCA amended alterations in Bax and Bcl-2 and reduced the activities of caspase-8, caspase-9, and caspase-3, indicating that it suppressed rotenone-induced apoptosis via modulating both intrinsic and extrinsic pathways. In conclusion, UDCA can be introduced as a novel approach for the management of Parkinson's disease via anti-apoptotic and anti-inflammatory mechanisms. These effects are probably linked to dopamine synthesis and mitochondrial regulation.