The recombinant carboxyl-terminal domain of the heavy chain of tetanus toxin (Hc-TeTx) exerts neuroprotective and neurorestorative effects on the dopaminergic system of animal models of Parkinson's disease (PD). The present study aimed to determine the effect of the Hc-TeTx fragment on the markers of oxidative stress and nitrosative stress generated by the acute toxicity of 1-methyl-4-phenylpyridinium (MPP⁺). For this purpose, the Hc-TeTx fragment was administered once a day in three 20 μg/kg consecutive injections into the grastrocnemius muscle of the rats, with an intra-striatal unilateral injection of 1 μL of MPP⁺ [10 μg/mL] then administered in order to cause a dopaminergic lesion. The results obtained show that the rats treated with Hc-TeTx plus MPP⁺ presented an increase in the expression of tyrosine hydroxylase (TH), a significantly greater decrease in the levels of the markers of oxidative stress, nitrosative stress, and neurodegeneration than that observed for the group injured with only MPP⁺. Moreover, it was observed that total superoxide dismutase (SOD) and copper/zinc SOD activity increased with the administration of Hc-TeTx. Finally, immunoreactivity levels were observed to decrease for the levels of 3-nitrotyrosine and the glial fibrillary acidic protein in the ipsilateral striatum of the rats treated with Hc-TeTx plus MPP⁺, in contrast with those lesioned with MPP⁺ alone. Our results demonstrate that the recombinant Hc-TeTx fragment may be a potent antioxidant and, therefore, could be suggested as a therapeutic tool against the dopaminergic neuronal impairment observed in the early stages of PD.

破伤风毒素重链 (Hc-TeTx) 的重组羧基末端结构域对帕金森病 (PD) 动物模型的多巴胺能系统发挥神经保护和神经恢复作用。本研究旨在确定 Hc-TeTx 片段对 1-甲基-4-苯基吡啶鎓 (MPP ⁺ )急性毒性产生的氧化应激和亚硝化应激标志物的影响。为此，Hc-TeTx 片段每天一次，分 3 次 20 μg/kg 连续注射到大鼠的腓肠肌中，纹状体内单侧注射 1 μL MPP ⁺ [10 μg/mL]，然后给药以引起多巴胺能损伤。所得结果表明，用 Hc-TeTx 加 MPP 治疗的大鼠⁺表现出酪氨酸羟化酶 (TH) 表达的增加，氧化应激、亚硝化应激和神经退行性变的标志物水平明显低于仅用 MPP ⁺损伤的组。此外，观察到总超氧化物歧化酶 (SOD) 和铜/锌 SOD 活性随着 Hc-TeTx 的施用而增加。最后，观察到用 Hc-TeTx 加 MPP ⁺治疗的大鼠的同侧纹状体中 3-硝基酪氨酸和胶质纤维酸性蛋白水平的免疫反应性水平降低，与用 MPP ⁺损伤的大鼠相比独自的。我们的研究结果表明，重组 Hc-TeTx 片段可能是一种有效的抗氧化剂，因此可以作为治疗 PD 早期观察到的多巴胺能神经元损伤的治疗工具。