关键词: 6-OHDA EAAT 1/2 GLUL L-Dopa PTEN ZnNP

Mesh : Animals Levodopa / pharmacology Oxidopamine Rats Neuroprotective Agents / pharmacology Zinc Oxide / chemistry pharmacology Disease Models, Animal Male Parkinson Disease / drug therapy metabolism Metal Nanoparticles / chemistry Nanoparticles / chemistry Parkinson Disease, Secondary / chemically induced drug therapy pathology metabolism Oxidative Stress / drug effects Rats, Wistar

来  源:   DOI:10.1038/s41598-024-69324-4   PDF(Pubmed)

Abstract:
Parkinson\'s disease (PD) is a chronic neurodegenerative case. As the disease progresses, the response time to doses of levodopa (L-Dopa) becomes shorter and the effects of the drug are severely limited by some undesirable side effects such as the \'on-off\' phenomenon. In several diseases, including Parkinson\'s, nanoparticles can deliver antioxidant compounds that reduce oxidative stress. This study evaluates and compares the neuroprotective effects of L-Dopa-modified zinc nanoparticles (ZnNPs) in the 6-hydroxydopamine (6-OHDA)-induced PD rat model. For this purpose, the synthesis of NPs was carried out. Scanning electron microscopy, X-ray diffraction and Fourier transform infrared spectrophotometer were used for characterization. The rats were randomized into 9 experimental groups: control, lesion group (6-OHDA), 6-OHDA + 5 mg/kg L-Dopa, 6-OHDA + 10 mg/kg L-Dopa, 6-OHDA + 20 mg/kg L-Dopa, 6-OHDA + 20 mg/kg ZnNPs, 6-OHDA + 40 mg/kg ZnNPs, 6-OHDA + 30 mg/kg ZnNPs + L-Dopa, and 6-OHDA + 60 mg/kg ZnNPs + L-Dopa. Behavioral tests were performed on all groups 14 days after treatment. Phosphatase and tensin homolog, Excitatory amino acid transporter 1/2, and Glutamine synthetase gene analyses were performed on brain samples taken immediately after the tests. In addition, histological and immunohistochemical methods were used to determine the general structure and properties of the tissues. We obtained important findings that L-Dopa-modified ZnNPs increased the activity of glutamate transporters. Our experiment showed that glutamate increases neuronal cell vitality and improves behavioral performance. Therefore, L-Dopa-modified ZnNPs can be used to prevent neurotoxicity. According to what we found, results show that L-Dopa-modified ZnNPs will lend to the effective avoidance and therapy of PD.
摘要:
帕金森病(PD)是一种慢性神经退行性疾病。随着疾病的进展,对左旋多巴(L-Dopa)剂量的响应时间变得更短,并且药物的作用受到一些不良副作用的严重限制,例如“开-关”现象。在几种疾病中,包括帕金森氏症,纳米颗粒可以提供减少氧化应激的抗氧化化合物。本研究评估和比较了L-Dopa修饰的锌纳米颗粒(ZnNPs)在6-羟基多巴胺(6-OHDA)诱导的PD大鼠模型中的神经保护作用。为此,进行NP的合成。扫描电子显微镜,使用X射线衍射和傅里叶变换红外分光光度计进行表征。将大鼠随机分为9个实验组:对照组,病变组(6-OHDA),6-OHDA+5mg/kg左旋多巴,6-OHDA+10mg/kg左旋多巴,6-OHDA+20mg/kg左旋多巴,6-OHDA+20mg/kgZnNPs,6-OHDA+40mg/kgZnNPs,6-OHDA+30毫克/千克ZnNPs+左旋多巴,和6-OHDA+60mg/kgZnNP+L-Dopa。治疗14天后对所有组进行行为测试。磷酸酶和张力蛋白同源物,对测试后立即采集的脑样品进行兴奋性氨基酸转运蛋白1/2和谷氨酰胺合成酶基因分析。此外,组织学和免疫组织化学方法用于确定组织的一般结构和性质。我们获得了重要发现,L-Dopa修饰的ZnNPs增加了谷氨酸转运体的活性。我们的实验表明,谷氨酸可以增加神经元细胞的活力并改善行为表现。因此,L-Dopa修饰的ZnNP可用于预防神经毒性。根据我们的发现,结果表明,左旋多巴修饰的ZnNPs将有助于有效避免和治疗PD。
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