Department of Medical Pharmacology, Faculty of Medicine, Malatya Turgut Ozal University, 44210, Battalgazi, Malatya, Turkey.
Department of Medical Pharmacology, Faculty of Medicine, Bilecik Şeyh Edebali University, Bilecik, Turkey.
Sci Rep. 2024 Aug 17;14(1):19077. doi: 10.1038/s41598-024-69324-4.
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.
帕金森病（PD）是一种慢性神经退行性疾病。随着疾病的发展，左旋多巴（L-Dopa）剂量的反应时间变得更短，并且药物的效果受到一些不良副作用的严重限制，例如“开-关”现象。在包括帕金森病在内的几种疾病中，纳米颗粒可以输送抗氧化化合物，以减少氧化应激。本研究评估和比较了左旋多巴修饰的锌纳米颗粒（ZnNPs）在 6-羟多巴胺（6-OHDA）诱导的 PD 大鼠模型中的神经保护作用。为此，进行了 NPs 的合成。使用扫描电子显微镜、X 射线衍射和傅里叶变换红外分光光度计进行了表征。大鼠被随机分为 9 个实验组：对照组、损伤组（6-OHDA）、6-OHDA+5mg/kg L-Dopa、6-OHDA+10mg/kg L-Dopa、6-OHDA+20mg/kg L-Dopa、6-OHDA+20mg/kg ZnNPs、6-OHDA+40mg/kg ZnNPs、6-OHDA+30mg/kg ZnNPs+L-Dopa 和 6-OHDA+60mg/kg ZnNPs+L-Dopa。治疗后 14 天对所有组进行行为测试。在测试后立即从大脑样本中进行磷酸酶和张力蛋白同系物、兴奋性氨基酸转运体 1/2 和谷氨酰胺合成酶基因分析。此外，还使用组织学和免疫组织化学方法来确定组织的一般结构和特性。我们获得了重要的发现，即左旋多巴修饰的 ZnNPs 增加了谷氨酸转运体的活性。我们的实验表明，谷氨酸增加神经元细胞活力并改善行为表现。因此，左旋多巴修饰的 ZnNPs 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 将有助于有效预防和治疗 PD。
