Enhanced Neuroprotective Effects of Coadministration of Tetrandrine with Glutathione in Preclinical Model of Parkinson’s Disease

Aim. In this study we examined the influence of tetrandrine (Tet) on the neuroprotective effects of glutathione (GSH) in the 6-hydroxydopamine- (6-OHDA-) lesioned rat model of Parkinson’s disease (PD). Methods. Levels in the redox system, dopamine (DA) metabolism, dopaminergic neuronal survival, and...

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Main Authors: Xiang-Yun Li, Guang-Hai Mei, Qiang Dong, Yu Zhang, Zhuang-Li Guo, Jing-Jing Su, Yu-Ping Tang, Xue-Hong Jin, Hou-Guang Zhou, Yan-Yan Huang
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:Parkinson's Disease
Online Access:http://dx.doi.org/10.1155/2015/931058
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author Xiang-Yun Li
Guang-Hai Mei
Qiang Dong
Yu Zhang
Zhuang-Li Guo
Jing-Jing Su
Yu-Ping Tang
Xue-Hong Jin
Hou-Guang Zhou
Yan-Yan Huang
author_facet Xiang-Yun Li
Guang-Hai Mei
Qiang Dong
Yu Zhang
Zhuang-Li Guo
Jing-Jing Su
Yu-Ping Tang
Xue-Hong Jin
Hou-Guang Zhou
Yan-Yan Huang
author_sort Xiang-Yun Li
collection DOAJ
description Aim. In this study we examined the influence of tetrandrine (Tet) on the neuroprotective effects of glutathione (GSH) in the 6-hydroxydopamine- (6-OHDA-) lesioned rat model of Parkinson’s disease (PD). Methods. Levels in the redox system, dopamine (DA) metabolism, dopaminergic neuronal survival, and apoptosis of the substantia nigra (SN) and striatum, as well as the rotational behavior of animals were examined after a 50-day administration of GSH + Tet (or GSH) and/or L-3,4-dihydroxyphenylalanine (L-dopa) to PD rats. Ethics Committee of Huashan Hospital, Fudan University approved the protocol (number SYXK2009-0082). Results. Administration of GSH or Tet alone did not show any significant effects on the factors evaluated in the PD rats. However, in the GSH + Tet group, we observed markedly decreased oxidative damage, inhibition of DA metabolism and enhanced DA synthesis, increased tyrosine hydroxylase- (TH-) immunopositive neuronal survival, and delayed apoptosis of dopaminergic neurons in the SN. Animal rotational behavior was improved in the GSH + Tet group. Additionally, coadministration of GSH + Tet appeared to offset the possible oxidative neurotoxicity induced by L-dopa. Conclusion. In this study, we demonstrated that tetrandrine allowed occurrence of the neuroprotective effect of glutathione probably due to inhibition of P-glycoprotein on 6-hydroxydopamine-lesioned rat models of Parkinson’s disease, including rats undergoing long-term L-dopa treatment.
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spelling doaj-art-8e6bcd45048349d287e122683e6ce6572025-02-03T01:02:33ZengWileyParkinson's Disease2090-80832042-00802015-01-01201510.1155/2015/931058931058Enhanced Neuroprotective Effects of Coadministration of Tetrandrine with Glutathione in Preclinical Model of Parkinson’s DiseaseXiang-Yun Li0Guang-Hai Mei1Qiang Dong2Yu Zhang3Zhuang-Li Guo4Jing-Jing Su5Yu-Ping Tang6Xue-Hong Jin7Hou-Guang Zhou8Yan-Yan Huang9Department of Geriatrics Neurology, Huashan Hospital, Fudan University, Shanghai 200040, ChinaDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, ChinaDepartment of Neurology, Huashan Hospital, Fudan University, Shanghai 200040, ChinaDepartment of Geriatrics Neurology, Huashan Hospital, Fudan University, Shanghai 200040, ChinaDepartment of Emergency Neurology, The Affiliated Hospital of Medical College Qingdao University, Qingdao 266021, ChinaDepartment of Neurology, Shanghai 9th People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200011, ChinaDepartment of Neurology, Huashan Hospital, Fudan University, Shanghai 200040, ChinaDepartment of Neurology, Suzhou Municipal Hospital Affiliated to Nanjing Medicine University, Suzhou 215001, ChinaDepartment of Geriatrics Neurology, Huashan Hospital, Fudan University, Shanghai 200040, ChinaDepartment of Geriatrics Neurology, Huashan Hospital, Fudan University, Shanghai 200040, ChinaAim. In this study we examined the influence of tetrandrine (Tet) on the neuroprotective effects of glutathione (GSH) in the 6-hydroxydopamine- (6-OHDA-) lesioned rat model of Parkinson’s disease (PD). Methods. Levels in the redox system, dopamine (DA) metabolism, dopaminergic neuronal survival, and apoptosis of the substantia nigra (SN) and striatum, as well as the rotational behavior of animals were examined after a 50-day administration of GSH + Tet (or GSH) and/or L-3,4-dihydroxyphenylalanine (L-dopa) to PD rats. Ethics Committee of Huashan Hospital, Fudan University approved the protocol (number SYXK2009-0082). Results. Administration of GSH or Tet alone did not show any significant effects on the factors evaluated in the PD rats. However, in the GSH + Tet group, we observed markedly decreased oxidative damage, inhibition of DA metabolism and enhanced DA synthesis, increased tyrosine hydroxylase- (TH-) immunopositive neuronal survival, and delayed apoptosis of dopaminergic neurons in the SN. Animal rotational behavior was improved in the GSH + Tet group. Additionally, coadministration of GSH + Tet appeared to offset the possible oxidative neurotoxicity induced by L-dopa. Conclusion. In this study, we demonstrated that tetrandrine allowed occurrence of the neuroprotective effect of glutathione probably due to inhibition of P-glycoprotein on 6-hydroxydopamine-lesioned rat models of Parkinson’s disease, including rats undergoing long-term L-dopa treatment.http://dx.doi.org/10.1155/2015/931058
spellingShingle Xiang-Yun Li
Guang-Hai Mei
Qiang Dong
Yu Zhang
Zhuang-Li Guo
Jing-Jing Su
Yu-Ping Tang
Xue-Hong Jin
Hou-Guang Zhou
Yan-Yan Huang
Enhanced Neuroprotective Effects of Coadministration of Tetrandrine with Glutathione in Preclinical Model of Parkinson’s Disease
Parkinson's Disease
title Enhanced Neuroprotective Effects of Coadministration of Tetrandrine with Glutathione in Preclinical Model of Parkinson’s Disease
title_full Enhanced Neuroprotective Effects of Coadministration of Tetrandrine with Glutathione in Preclinical Model of Parkinson’s Disease
title_fullStr Enhanced Neuroprotective Effects of Coadministration of Tetrandrine with Glutathione in Preclinical Model of Parkinson’s Disease
title_full_unstemmed Enhanced Neuroprotective Effects of Coadministration of Tetrandrine with Glutathione in Preclinical Model of Parkinson’s Disease
title_short Enhanced Neuroprotective Effects of Coadministration of Tetrandrine with Glutathione in Preclinical Model of Parkinson’s Disease
title_sort enhanced neuroprotective effects of coadministration of tetrandrine with glutathione in preclinical model of parkinson s disease
url http://dx.doi.org/10.1155/2015/931058
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