title: Enhanced Neuroprotective Effects of Coadministration of Tetrandrine with Glutathione in Preclinical Model of Parkinson's Disease.
abstract: 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.
authors.affiliation: Department of Geriatrics Neurology, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Xiang-Yun
authors.initials: XY
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Guang-Hai
authors.initials: GH
authors.lastname: Mei
authors.affiliation: Department of Neurology, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Dong
authors.affiliation: Department of Geriatrics Neurology, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Emergency Neurology, The Affiliated Hospital of Medical College Qingdao University, Qingdao 266021, China.
authors.forename: Zhuang-Li
authors.initials: ZL
authors.lastname: Guo
authors.affiliation: Department of Neurology, Shanghai 9th People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Su
authors.affiliation: Department of Neurology, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Tang
authors.affiliation: Department of Neurology, Suzhou Municipal Hospital Affiliated to Nanjing Medicine University, Suzhou 215001, China.
authors.forename: Xue-Hong
authors.initials: XH
authors.lastname: Jin
authors.affiliation: Department of Geriatrics Neurology, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Hou-Guang
authors.initials: HG
authors.lastname: Zhou
authors.affiliation: Department of Geriatrics Neurology, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Huang