BBPT 通过调节初级神经元和帕金森病大鼠模型中的氧化应激、凋亡和炎症蛋白,减轻了 6-OHDA 引起的毒性。

IF 3.4 3区 医学 Q2 NEUROSCIENCES
Jyoti Mishra, Vaishali Walecha, Tuithung Sophronea, Ankit Singh, Saurabh Agrawal, Pratibha Mehta Luthra
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引用次数: 0

摘要

帕金森病(Parkinson's disease,PD)是由黑质紧密团(substantia nigra pars compacta,SNpc)中的多巴胺能神经元变性引起的。通过纹状体-苍白球通路发挥作用的腺苷 A2AR 已成为治疗帕金森病的非多巴胺能靶点。本研究探讨了(4E)-4-(4-溴亚苄基氨基)-3-苯基-2,3-二氢-2-硫酮-噻唑-5-甲腈(BBPT)的抗帕金森病潜力。BBPT 具有明显的原位抗氧化活性。在 MTT 试验中,BBPT 处理对原发性中脑神经元(PMDN)细胞的毒性不明显。用 BBPT 处理 6-OHDA 诱导的 PMDN 细胞 3 小时后,细胞存活率达到 80-85%,多巴胺和 TNF-α 水平得到恢复。BBPT 的急性和亚急性毒性试验以 Sprague Dawley(SD)大鼠为对象。在毒性试验中,未观察到大鼠出现任何明显的体征、血液学或生化变化。为了评估 BBPT 在体内的作用,我们建立了 6-OHDA 诱导的单侧病变 SD 大鼠帕金森病模型。我们观察到,BBPT 治疗改善了 6-OHDA 诱导的单侧病变大鼠的行为症状。我们从6-OHDA诱导的BBPT治疗大鼠脑组织中分离出蛋白质,以评估其抗氧化作用(GSH、过氧化氢酶、SOD、脂质过氧化反应、亚硝酸盐)、多巴胺水平以及细胞凋亡和炎症的恢复情况。我们的研究结果表明,BBPT提高了单侧病变6-OHDA诱导的SD大鼠的抗氧化酶水平,恢复了caspase-3/Bcl-2水平以阻止细胞凋亡,并降低了TNF-α/IL-6水平,从而恢复了神经元损伤。准确地说,这些研究结果表明,BBPT具有显著的抗帕金森病活性,并具有预防多巴胺能神经变性的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
BBPT attenuated 6-OHDA-induced toxicity by modulating oxidative stress, apoptotic, and inflammatory proteins in primary neurons and rat models of Parkinson's disease

Parkinson’s disease (PD) results from the degeneration of dopaminergic neurons in substantia nigra pars compacta (SNpc). Adenosine A2AR acting through the striato-pallidal pathway has emerged as a non-dopaminergic target in the therapy of PD. In the present work, the anti-parkinsonian potential of (4E)-4-(4-bromobenzylideneamino)-3-phenyl-2,3-dihydro-2-thioxo- thiazole-5-carbonitrile (BBPT) was explored. BBPT exhibited significant antioxidant activity in situ. In the MTT assay, the BBPT treatment showed insignificant toxicity to the primary midbrain neuronal (PMDN) cells. 6-OHDA induced PMDN cells, 3 h post-treated with BBPT showed 80–85 % survival of the cells and restoration of dopamine and TNF-α levels. The acute and sub-acute toxicity test for BBPT was performed with Sprague Dawley (SD) rats. In toxicity assay, any significant physical, hematological, or biochemical changes in the rats were not observed. To evaluate the effect of BBPT in vivo, a 6-OHDA-induced unilaterally lesioned SD rat model of PD was established. We observed that the BBPT treatment improved the behavioral symptoms in 6-OHDA-induced unilaterally lesioned rats. The proteins of 6-OHDA-induced BBPT-treated rats were isolated from the brain tissue to assess the antioxidant effect (GSH, catalase, SOD, lipid-peroxidation, nitrite), dopamine levels, and the restoration in the apoptosis and inflammation. Our results demonstrated that BBPT increased the anti-oxidant enzyme levels, restored the caspase-3/Bcl-2 levels to arrest apoptosis, and attenuated the TNF-α/IL-6 levels, thus restoring the neuronal damage in unilaterally lesioned 6-OHDA-induced SD rats. Precisely, the findings suggested that BBPT possessed significant anti-parkinsonian activity and has the potential to prevent dopaminergic neurodegeneration.

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来源期刊
Neurotoxicology
Neurotoxicology 医学-毒理学
CiteScore
6.80
自引率
5.90%
发文量
161
审稿时长
70 days
期刊介绍: NeuroToxicology specializes in publishing the best peer-reviewed original research papers dealing with the effects of toxic substances on the nervous system of humans and experimental animals of all ages. The Journal emphasizes papers dealing with the neurotoxic effects of environmentally significant chemical hazards, manufactured drugs and naturally occurring compounds.
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