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Neuroprotective effects of boron nitride nanoparticles in the experimental Parkinson's disease model against MPP+ induced apoptosis.
Metabolic Brain Disease ( IF 3.6 ) Pub Date : 2020-03-25 , DOI: 10.1007/s11011-020-00559-6
Recep Küçükdoğru 1 , Hasan Türkez 1 , Mehmet Enes Arslan 1 , Özlem Özdemir Tozlu 1 , Erdal Sönmez 2 , Adil Mardinoğlu 3, 4 , Ivana Cacciatore 5 , Antonio Di Stefano 5
Affiliation  

Parkinson’s disease (PD) is one of the most aggressive neurodegenerative diseases and characterized by the loss of dopamine-sensitive neurons in the substantia nigra region of the brain. There is no any definitive treatment to completely cure PD and existing treatments can only ease the symptoms of the disease. Boron nitride nanoparticles have been extensively studied in nano-biological studies and researches showed that it can be a promising candidate for PD treatment with its biologically active unique properties. In the present study, it was aimed to investigate ameliorative effects of hexagonal boron nitride nanoparticles (hBNs) against toxicity of 1-methyl-4-phenylpyridinium (MPP+) in experimental PD model. Experimental PD model was constituted by application of MPP+ to differentiated pluripotent human embryonal carcinoma cell (Ntera-2, NT-2) culture in wide range of concentrations (0.62 to 2 mM). Neuroprotective activity of hBNs against MPP+ toxicity was determined by cell viability assays including MTT and LDH release. Oxidative alterations by hBNs application in PD cell culture model were investigated using total antioxidant capacity (TAC) and total oxidant status (TOS) tests. The impacts of hBNs and MPP+ on nuclear integrity were analyzed by Hoechst 33258 fluorescent staining method. Acetylcholinesterase (AChE) enzyme activities were determined by a colorimetric assay towards to hBNs treatment. Cell death mechanisms caused by hBNs and MPP+ exposure was investigated by flow cytometry analysis. Experimental results showed that application of hBNs increased cell viability in PD model against MPP+ application. TAS and TOS analysis were determined that antioxidant capacity elevated after hBNs applications while oxidant levels were reduced. Furthermore, flow cytometric analysis executed that MPP+ induced apoptosis was prevented significantly (p < 0.05) after application with hBNs. In a conclusion, the obtained results indicated that hBNs have a huge potential against MPP+ toxicity and can be used in PD treatment as novel neuroprotective agent and drug delivery system.



中文翻译:

氮化硼纳米颗粒在实验性帕金森病模型中对 MPP+ 诱导的细胞凋亡的神经保护作用。

帕金森病 (PD) 是最具侵袭性的神经退行性疾病之一,其特征是大脑黑质区域多巴胺敏感神经元的丧失。没有任何确定的治疗方法可以完全治愈 PD,现有的治疗方法只能缓解疾病的症状。氮化硼纳米粒子已在纳米生物学研究中得到广泛研究,研究表明,它具有独特的生物活性特性,是治疗 PD 的有希望的候选者。在本研究中,旨在研究六方氮化硼纳米颗粒 (hBN ) 在实验性 PD 模型中对 1-甲基-4-苯基吡啶 (MPP + )毒性的改善作用。应用MPP +构建实验PD模型分化的多能人胚胎癌细胞(Ntera-2、NT-2)培养物,浓度范围很广(0.62 至 2 mM)。hBN 对 MPP +毒性的神经保护活性是通过细胞活力测定(包括 MTT 和 LDH 释放)确定的。使用总抗氧化能力 (TAC) 和总氧化状态 (TOS) 测试研究 hBN 在 PD 细胞培养模型中应用的氧化改变。hBNs 和 MPP +的影响Hoechst 33258 荧光染色法分析细胞核完整性。乙酰胆碱酯酶 (AChE) 酶活性通过对 hBN 处理的比色测定来确定。通过流式细胞术分析研究了 hBN 和 MPP+ 暴露引起的细胞死亡机制。实验结果表明,hBNs 的应用增加了 PD 模型中的细胞活力,以对抗 MPP +应用。TAS 和 TOS 分析确定应用 hBNs 后抗氧化能力提高,而氧化剂水平降低。此外,流式细胞术分析表明 MPP +诱导的细胞凋亡被显着阻止(p < 0.05) 应用 hBN 后。总之,所获得的结果表明 hBN 具有巨大的抗 MPP +毒性潜力,可作为新型神经保护剂和药物递送系统用于 PD 治疗。

更新日期:2020-03-25
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