Department of Anesthesia, En Chu Kon Hospital, Sanshia District, 23702, New Taipei City, Taiwan, Republic of China.
Department of Neurosurgery, Mackay Memorial Hospital, 10449, Taipei, Taiwan, Republic of China.
Neurotox Res. 2021 Jun;39(3):774-786. doi: 10.1007/s12640-021-00333-1. Epub 2021 Feb 1.
Animal models of haloperidol (HAL)-induced neurotoxicity and orofacial dyskinesia (OD) have long been used to study human tardive dyskinesia (TD). Similar to patients with TD, these models show strong pathophysiological characteristics such as striatal oxidative stress and neural cytoarchitecture alteration. Naringin (NAR), a bioflavonoid commonly found in citrus fruits, has potent antioxidative, anti-inflammatory, antiapoptotic, and neuroprotective properties. The present study evaluated the potential protective effects of NAR against HAL-induced OD in rats and the neuroprotective mechanisms underlying these effects. HAL treatment (1 mg/kg i.p. for 21 successive days) induced OD development, characterized by increased vacuous chewing movement (VCM) and tongue protrusion (TP), which were recorded on the 7th, 14th, and 21st day of drug treatment. NAR (30, 100, and 300 mg/kg) was administered orally 60 min before HAL injection for 21 successive days. On the 21st day, after behavioral testing, the rats were sacrificed, and the nitrosative and oxidative status, antioxidation power, neurotransmitter levels, neuroinflammation, and apoptotic markers in the striatum were measured. HAL induced OD development, with significant increases in the frequency of VCM and TP. NAR treatment (100 and 300 mg/kg) prevented HAL-induced OD significantly. Additionally, NAR treatment reduced the HAL-induced nitric oxide and lipid peroxide production, increased the antioxidation power and neurotransmitter levels in the striatum, and significantly reduced the levels of neuroinflammatory and apoptotic markers. Our results first demonstrate the neuroprotective effects of NAR against HAL-induced OD, suggesting that NAR may help in delaying or treating human TD in clinical settings.
动物模型已被广泛应用于研究人类迟发性运动障碍（TD），其中包括氟哌啶醇（HAL）诱导的神经毒性和口面部运动障碍（OD）。这些模型与 TD 患者具有相似的强生理病理学特征，如纹状体氧化应激和神经细胞结构改变。柚皮苷（NAR）是一种常见于柑橘类水果的生物类黄酮，具有强大的抗氧化、抗炎、抗凋亡和神经保护特性。本研究评估了 NAR 对 HAL 诱导的大鼠 OD 的潜在保护作用及其潜在的神经保护机制。HAL 处理（1mg/kg 腹腔注射，连续 21 天）诱导 OD 发展，表现为空嚼运动（VCM）和伸舌（TP）增加，在药物治疗的第 7、14 和 21 天记录。NAR（30、100 和 300mg/kg）连续 21 天在 HAL 注射前 60 分钟口服给药。在第 21 天行为测试后，处死大鼠，测量纹状体的硝化和氧化状态、抗氧化能力、神经递质水平、神经炎症和凋亡标志物。HAL 诱导 OD 发展，VCM 和 TP 的频率显著增加。NAR 治疗（100 和 300mg/kg）显著预防了 HAL 诱导的 OD。此外，NAR 治疗降低了 HAL 诱导的一氧化氮和脂质过氧化物的产生，增加了纹状体的抗氧化能力和神经递质水平，并显著降低了神经炎症和凋亡标志物的水平。我们的研究结果首次证明了 NAR 对 HAL 诱导的 OD 的神经保护作用，表明 NAR 可能有助于在临床环境中延缓或治疗人类 TD。
