Toxicity Induced by Madopar (l-DOPA) during Curing Parkinson’s Disease by Inhibiting Mitochondrial Function and AKT Pathway
Journal Title: Journal of Pharmaceutical and Biomedical Sciences - Year 2016, Vol 6, Issue 4
Abstract
Madopar is an effective drug being used clinically for curing Parkinson’s disease (PD) nowadays. However, a growing number of studies found that the Madopar has a falling trend in curative effect including dyskinesia and the reasons are still unknown very well. In order to invest the reasons, we constructed 6-OHDA-induced rat PD model including control group, 6-OHDA group and Madopar + 6-OHDA group, respectively. We detected the behaviour of rotation and roll-rod behaviours 2 weeks later, and the results showed no protection effect and appeared SD rats’ abnormal behaviours. l-dopa treated SH-SY5Y cells for 48 h, cell viability has been inhibited and level of ROS in mitochondria has increased. By detecting levels of apoptosis-related proteins, p-AKT/AKT and Bax/Bcl2 found l-dopa-induced cell apoptosis and death. The decreasing of Sirt3 in mitochondria with the treat of l-DOPA suggests a relationship with mitochondrial function. In a word, the inhibition function of mitochondria and apoptosis in DA neuron cell was the main reasons of l-dopa, which played a weak role in anti-PD.
Authors and Affiliations
Rong-Rong He, Ting-Mei Wang, Hiroshi Kurihara, Yi-Fang Li
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