| Title |
Additive Protective Effects of Donepezil and Nicotine Against Salsolinol-Induced Cytotoxicity in SH-SY5Y Cells
|
|---|---|
| Published in |
Neurotoxicity Research, March 2009
|
| DOI | 10.1007/s12640-009-9040-2 |
| Pubmed ID | |
| Authors |
Jharna R. Das, Yousef Tizabi |
| Abstract |
Although the etiology of Parkinson's disease (PD) remains elusive, a number of toxins including elevated salsolinol, an endogenous metabolite of dopamine may contribute to its pathology. It was reported recently that nicotine may have protective effects against salsolinol-induced toxicity in human neuroblastoma derived SH-SY5Y cells and that these effects of nicotine are mediated by nicotinic receptors. Donepezil (Aricept) is a reversible non-competitive acetylcholinesterase inhibitor that is approved for use in mild to moderate Alzheimer's disease. The increase in acetylcholine concentrations is believed to be the major contributory factor in donepezil's therapeutic efficacy. However, cholinesterase inhibitors may also directly interact with nicotinic receptors and possess neuroprotective properties. In this study, we sought to determine whether donepezil may have protective effects against salsolinol-induced toxicity in SH-SY5Y cells and whether the combination of donepezil and nicotine may result in additive protection. Moreover, it was of interest to elucidate the role of nicotinic receptors as well as cell cycle and apoptosis in mechanism of action of these compounds. SH-SY5Y cells were exposed to 0.6 mM salsolinol with and without various drug pretreatments for 48 h. Nicotine (50 muM) resulted in approximately 54% protection and donepezil (5 muM) resulted in approximately 40% protection, and the combination of the two resulted in an additive (approximately 93%) protection against salsolinol-induced toxicity. Salsolinol caused an arrest of the cells in G(1)-phase of cell cycle and an increase in apoptotic indices that were blocked by the combination of donepezil and nicotine. Mecamylamine, a non-selective nicotinic receptor antagonist completely blocked the effects of nicotine and partially attenuated the effects of donepezil. A combination of atropine, a muscarinic receptor antagonist and mecamylamine completely blocked the effects of donepezil, indicating involvement of both nicotinic and muscarinic receptors in donepezil's actions. The findings suggest a therapeutic potential for the combination of donepezil and nicotine in PD. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 34 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 3% |
| United States | 1 | 3% |
| Unknown | 32 | 94% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 6 | 18% |
| Researcher | 4 | 12% |
| Student > Postgraduate | 4 | 12% |
| Professor > Associate Professor | 3 | 9% |
| Student > Master | 3 | 9% |
| Other | 9 | 26% |
| Unknown | 5 | 15% |
| Readers by discipline | Count | As % |
|---|---|---|
| Pharmacology, Toxicology and Pharmaceutical Science | 8 | 24% |
| Agricultural and Biological Sciences | 6 | 18% |
| Neuroscience | 5 | 15% |
| Medicine and Dentistry | 4 | 12% |
| Biochemistry, Genetics and Molecular Biology | 3 | 9% |
| Other | 3 | 9% |
| Unknown | 5 | 15% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 19 April 2013.
All research outputs
#15,270,134
of 22,707,247 outputs
Outputs from Neurotoxicity Research
#533
of 873 outputs
Outputs of similar age
#79,311
of 93,822 outputs
Outputs of similar age from Neurotoxicity Research
#20
of 21 outputs
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