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使用小鼠评估磷酸吡哆醛在氯丙嗪诱发帕金森症中的作用

An Evaluation of the Effects of Pyridoxal Phosphate in Chlorpromazineinduced Parkinsonism using Mice.

作者信息

Olofinnade Anthony T, Onaolapo Tolulope M, Oladimeji Samad, Fatoki Adetunji M, Balogun Covenant I, Onaolapo Adejoke Y, Onaolapo Olakunle J

机构信息

Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Clinical Sciences, College of Medicine, Lagos State University, Ikeja, Lagos State, Nigeria.

Behavioural Neuroscience/Neuropharmacology Unit, Department of Pharmacology, Ladoke Akintola University of Technology, Osogbo, Osun State, Nigeria.

出版信息

Cent Nerv Syst Agents Med Chem. 2020;20(1):13-25. doi: 10.2174/1871524920666200120142508.

DOI:10.2174/1871524920666200120142508
PMID:31987026
Abstract

BACKGROUND

Parkinsonism is a neurodegenerative disorder with a heavy disease burden, despite the discovery and application of drugs. Current research is beginning to suggest the possible crucial roles of micronutrients such as pyridoxal phosphate in the prevention or management of neurodegenerative disorders.

OBJECTIVE

We investigated the possible protective effects of supplemental pyridoxal phosphate in Chlorpromazine (CPZ)-induced Parkinsonism-like changes in mice.

METHODS

Mice were assigned to eight groups of 30 mice each. Groups included Vehicle control (fed standard diet (SD), and administered intraperitoneal {ip} injection of saline and saline per orem), levodopa-carbidopa (LD) group (SD, saline ip and LD per orem), two groups fed pyridoxal phosphate-supplemented diet (at 100 and 200 mg/kg of feed), and administered saline both ip and orally, CPZ group (SD, CPZ ip and saline per orem), CPZ/LD group (SD, CPZ ip and LD per orem) and finally two groups fed pyridoxal phosphate -supplemented diet (at 100 and 200 mg/kg of feed) and administered CPZ ip plus saline per orem. Treatments were administered daily for a period of 21 days to allow for the induction of Parkinsonism features. Body weight and food intake were measured weekly while neurobehavioural and biochemical tests were assessed at the end of the experimental period.

RESULTS

Pyridoxal phosphate supplementation was associated with a reduction in CPZ-induced suppression of open-field horizontal locomotion and rearing; and a significant increase in grooming activity. Administration of pyridoxal phosphate-supplemented diet was also associated with improvements in working-memory in CPZ-treated mice; and there was reduction in the index of anxiety and catalepsy score.

CONCLUSION

Pyridoxal phosphate supplementation was associated with significant benefits in CPZ-induced Parkinsonism-like changes in mice.

摘要

背景

尽管已发现并应用了药物,但帕金森症是一种疾病负担沉重的神经退行性疾病。目前的研究开始表明,诸如磷酸吡哆醛等微量营养素在神经退行性疾病的预防或管理中可能发挥关键作用。

目的

我们研究了补充磷酸吡哆醛对氯丙嗪(CPZ)诱导的小鼠帕金森症样变化可能具有的保护作用。

方法

将小鼠分为八组,每组30只。分组包括溶剂对照组(喂食标准饮食(SD),腹腔注射生理盐水和口服生理盐水)、左旋多巴 - 卡比多巴(LD)组(SD,腹腔注射生理盐水和口服LD)、两组喂食补充磷酸吡哆醛的饮食(每千克饲料含100和200毫克),并腹腔和口服给予生理盐水,CPZ组(SD,腹腔注射CPZ和口服生理盐水),CPZ/LD组(SD,腹腔注射CPZ和口服LD),最后两组喂食补充磷酸吡哆醛的饮食(每千克饲料含100和200毫克),并腹腔注射CPZ加口服生理盐水。每天进行治疗,持续21天以诱导帕金森症特征。每周测量体重和食物摄入量,同时在实验期结束时评估神经行为和生化测试。

结果

补充磷酸吡哆醛与CPZ诱导的旷场水平运动和竖毛行为抑制的减轻相关;并且梳理活动显著增加。给予补充磷酸吡哆醛的饮食还与CPZ处理小鼠的工作记忆改善相关;并且焦虑指数和僵住症评分降低。

结论

补充磷酸吡哆醛与CPZ诱导的小鼠帕金森症样变化的显著益处相关。

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