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.
Highlights
Parkinson’s disease (PD), characterized by the progressive loss of dopaminergic neurons mainly in the substantia nigra (SN) [1], is a common neurodegenerative disease
Rotational tests were performed on the PD rats for the second time
To determine whether apoptosis was involved in the observed loss of dopaminergic neurons, we further examined the ultrastructure of dopaminergic neurons using TEM
Summary
Parkinson’s disease (PD), characterized by the progressive loss of dopaminergic neurons mainly in the substantia nigra (SN) [1], is a common neurodegenerative disease. The etiopathogenesis of PD remains unclear, oxidative stress and mitochondrial dysfunction are recognized as key events in dopaminergic neuronal loss [2, 3]. It was found to be the earliest known abnormal change in nigrostriatal degeneration of PD patients, followed by decreased mitochondrial complex I (CI) activity and DA levels [6, 7]. GSH levels and DA content are not selectively damaged in either SN, other brain areas of PD patients, or other diseases involving dopaminergic pathway [8, 9]. Parkinson’s Disease restoration of GSH level in SN, aiming at protecting DA neurons from oxidative stress injuries, might be a potential alternative treatment for PD
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