Laboratorio de Neurofarmacología, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Puebla, Mexico.
Laboratorio de Neuroquímica, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, 14 Sur y Av. San Claudio CU, Col. San Manuel, 72570, Puebla, Mexico.
Neurotox Res. 2019 Apr;35(3):699-710. doi: 10.1007/s12640-018-9990-3. Epub 2019 Jan 3.
Reports indicate that striatal dopaminergic damage induced by 6-hydoxydopamine (6-OHDA) can be blocked by C-terminal domain of tetanus toxin (Hc-TeTx), suggesting possible therapeutic potential of Hc-TeTx in Parkinson's disease (PD). Pramipexole (PPX), a D2/D3 dopaminergic agonist, is currently used in PD treatment. The purpose of this study was to gain some understanding of the actions of each drug, including potential antioxidant and anti-inflammatory effects and importantly, to determine whether the combination of the two drugs would be superior to each alone. Adult male Wistar rats were administered 6-OHDA into the dorso-lateral striatum, and the effects of Hc-TeTx fragment (20 μg/kg i.m. every 24 h) for 3 days; PPX (1 mg/kg p.o., every 12 h) for 30 days and their combination on various motor and neurochemical parameters were evaluated. Behavioral tests were carried out at 15 and 30 days post-treatments. At day 31, the animals were sacrificed and the levels of tyrosine hydroxylase (TH), reflecting dopaminergic activity in both striatum and substantia nigra, were evaluated. In addition, indices of astrogliosis, microgliosis, as well as oxidative stress in the striatum were determined. Both Hc-TeTx and PPX ameliorated the motor and neurochemical deficits induced by 6-OHDA lesion; however, the combination of the two drugs was not superior to each alone. Hence, at concentrations used in this study, no significant advantage in combining Hc-TeTx with PPX was noted. Although the results suggest similar neurochemical effects of the two compounds, further evaluation of different concentrations of Hc-TeTx and PPX as potential intervention in PD is warranted.
报告表明，6-羟多巴胺（6-OHDA）诱导的纹状体多巴胺能损伤可被破伤风毒素 C 端结构域（Hc-TeTx）阻断，这表明 Hc-TeTx 在帕金森病（PD）中具有潜在的治疗潜力。普拉克索（PPX），一种 D2/D3 多巴胺能激动剂，目前用于 PD 治疗。本研究旨在了解每种药物的作用，包括潜在的抗氧化和抗炎作用，重要的是，确定两种药物的联合使用是否优于单独使用。成年雄性 Wistar 大鼠经侧纹状体注射 6-OHDA，给予 Hc-TeTx 片段（20μg/kg 肌内注射，每 24 小时 1 次）3 天；PPX（1mg/kg 口服，每 12 小时 1 次）30 天，评估两种药物及其组合对各种运动和神经化学参数的影响。在治疗后 15 和 30 天进行行为测试。在第 31 天，处死动物，评估纹状体和黑质中反映多巴胺能活性的酪氨酸羟化酶（TH）水平。此外，还测定了纹状体中星形胶质细胞增生、小胶质细胞增生以及氧化应激的指标。Hc-TeTx 和 PPX 均改善了 6-OHDA 损伤引起的运动和神经化学缺陷；然而，两种药物的联合使用并不优于单独使用。因此，在本研究中使用的浓度下，将 Hc-TeTx 与 PPX 联合使用没有明显优势。尽管结果表明两种化合物具有相似的神经化学作用，但需要进一步评估不同浓度的 Hc-TeTx 和 PPX 作为 PD 潜在干预的作用。
