Khan Urooj Ahmed, Warsi Musarrat Husain, Alkreathy Huda Mohammed, Karim Shahid, Jain Gaurav Kumar, Ali Asgar
Department of Pharmaceutics, School of Pharmaceutical Education and Research, New Delhi, India.
Department of Pharmaceutics, Dr. Ram Manohar Lohia College of Pharmacy, Ghaziabad, Uttar Pradesh, India.
Front Pharmacol. 2023 May 30;14:1188470. doi: 10.3389/fphar.2023.1188470. eCollection 2023.
Cerium oxide nanoparticles (CONPs) have been investigated for their therapeutic potential in Parkinson's disease (PD) due to their potent and regenerative antioxidant activity. In the present study, CONPs were used to ameliorate the oxidative stress caused by free radicals in haloperidol-induced PD in rats following intranasal administration. The antioxidant potential of the CONPs was evaluated using ferric reducing antioxidant power (FRAP) assay. The penetration and local toxicity of the CONPs was evaluated using goat nasal mucosa. The acute local toxicity of intranasal CONPs was also studied in rat. Gamma scintigraphy was used to assess the targeted brain delivery of CONPs. Acute toxicity studies were performed in rats to demonstrate safety of intranasal CONPs. Further, open field test, pole test, biochemical estimations and brain histopathology was performed to evaluate efficacy of intranasal CONPs in haloperidol-induced PD rat model. The FRAP assay revealed highest antioxidant activity of prepared CONPs at a concentration of 25 μg/mL. Confocal microscopy showed deep and homogenous distribution of CONPs in the goat nasal mucus layers. No signs of irritation or injury were seen in goat nasal membrane when treated with optimized CONPs. Scintigraphy studies in rats showed targeted brain delivery of intranasal CONPs and acute toxicity study demonstrated safety. The results of open field and pole test showed highly significant ( < 0.001) improvement in locomotor activity of rats treated with intranasal CONPs compared to untreated rats. Further, brain histopathology of treatment group rats showed reduced neurodegeneration with presence of more live cells. The amount of thiobarbituric acid reactive substances (TBARS) was reduced significantly, whereas the levels of catalase (CAT), superoxide dismutase (SOD), and GSH were increased significantly, while amounts of interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) showed significant reduction after intranasal administration of CONPs. Also, the intranasal CONPs, significantly high ( < 0.001) dopamine concentration (13.93 ± 0.85 ng/mg protein) as compared to haloperidol-induced control rats (5.76 ± 0.70 ng/mg protein). The overall results concluded that the intranasal CONPs could be safe and effective therapeutics for the management of PD.
由于其强大的再生抗氧化活性，氧化铈纳米颗粒（CONPs）已被研究其在帕金森病（PD）中的治疗潜力。在本研究中，通过鼻内给药，使用CONPs改善大鼠中由氟哌啶醇诱导的帕金森病中自由基引起的氧化应激。使用铁还原抗氧化能力（FRAP）测定法评估CONPs的抗氧化潜力。使用山羊鼻黏膜评估CONPs的穿透性和局部毒性。还在大鼠中研究了鼻内CONPs的急性局部毒性。使用γ闪烁扫描术评估CONPs在脑中的靶向递送。在大鼠中进行急性毒性研究以证明鼻内CONPs的安全性。此外，进行旷场试验、杆试验、生化评估和脑组织病理学检查，以评估鼻内CONPs在氟哌啶醇诱导的帕金森病大鼠模型中的疗效。FRAP测定显示，制备的CONPs在浓度为25μg/mL时具有最高的抗氧化活性。共聚焦显微镜显示CONPs在山羊鼻黏液层中分布深且均匀。用优化的CONPs处理时，在山羊鼻黏膜中未见刺激或损伤迹象。大鼠中的闪烁扫描研究显示鼻内CONPs在脑中的靶向递送，急性毒性研究证明了安全性。旷场试验和杆试验的结果显示，与未处理的大鼠相比，鼻内给予CONPs的大鼠的运动活性有极显著（<0.001）改善。此外，治疗组大鼠的脑组织病理学显示神经退行性变减少，活细胞数量增加。鼻内给予CONPs后，硫代巴比妥酸反应性物质（TBARS）的量显著减少，而过氧化氢酶（CAT）、超氧化物歧化酶（SOD）和谷胱甘肽（GSH）的水平显著增加，白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的量显著减少。此外，与氟哌啶醇诱导的对照大鼠（5.76±0.70ng/mg蛋白质）相比，鼻内CONPs的多巴胺浓度显著高（<0.001）（13.93±0.85ng/mg蛋白质）。总体结果表明，鼻内CONPs可能是治疗帕金森病的安全有效的疗法。
