Abstract
It is well established that combination of heavy drinking and smoking has severe health consequences. However, at relatively low concentrations, both alcohol and nicotine may have beneficial effects including neuroprotection. Thus, protective effects of low alcohol concentration against beta-amyloid-induced toxicity in organotypic hippocampal slices and protective effects of nicotine against salsolinol-induced toxicity in human-derived neuroblastoma cells (SH-SY5Y) have been reported. In this study, we sought to determine whether alcohol might also be protective against salsolinol-induced toxicity in SH-SY5Y cells and whether the combination of low doses of alcohol and nicotine might have an additive or synergistic effect. Pre-exposure of SH-SY5Y cells to either ethanol (1 or 10 mM) or nicotine (20 or 50 μM) significantly attenuated salsolinol-induced toxicity. However, contrary to the expectation the combination of low doses of alcohol and nicotine not only did not provide any synergistic or additive protective effect, but exacerbated salsolinol-induced toxicity. Indeed, simple combination of low alcohol and nicotine resulted in significant toxicity in SH-SY5Y cells. This toxicity, reflected in a reduction in cell viability was associated with an increase in apoptosis as determined by caspase-3 measurement. These in vitro results suggest that combination of even low concentrations of alcohol and nicotine may activate apoptotic mechanisms that can lead to cell toxicity and detrimental consequences.
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References
Belmadani A, Kumar S, Schipma M, Collins MA, Neafsey EJ (2004) Inhibition of amyloid-beta-induced neurotoxicity and apoptosis by moderate ethanol preconditioning. Neuroreport 15:2093–2096
Collins MA, Neafsey EJ, Mukamal KJ, Gray MO, Parks DA et al (2009) Alcohol in moderation, cardioprotection, and neuroprotection: epidemiological considerations and mechanistic studies. Alcohol Clin Exp Res 33:206–219
Copeland RL Jr, Leggett YA, Kanaan YM, Taylor RE, Tizabi Y (2005) Neuroprotective effects of nicotine against salsolinol-induced cytotoxicity: implications for Parkinson’s disease. Neurotox Res 8:289–293
Copeland RL Jr, Das JR, Kanaan YM, Taylor RE, Tizabi Y (2007) Antiapoptotic effects of nicotine in its protection against salsolinol-induced cytotoxicity. Neurotox Res 12:61–69
Das JR, Tizabi Y (2009) Additive protective effects of donepezil and nicotine against salsolinol-induced cytotoxicity in SH-SY5Y cells. Neurotox Res 16:194–204
Dopico AM, Lovinger DM (2009) Acute alcohol action and desensitization of ligand-gated ion channels. Pharmacol Rev 61:98–114
Guan ZZ, Yu WF, Nordberg A (2003) Dual effects of nicotine on oxidative stress and neuroprotection in PC12 cells. Neurochem Int 43:243–249
Hejmadi MV, Dajas-Bailador F, Barns SM, Jones B, Wonnacott S (2003) Neuroprotection by nicotine against hypoxia-induced apoptosis in cortical cultures involves activation of multiple nicotinic acetylcholine receptor subtypes. Mol Cell Neurosci 24:779–786
Liu Q, Zhao B (2004) Nicotine attenuates beta-amyloid peptide-induced neurotoxicity, free radical and calcium accumulation in hippocampal neuronal cultures. Br J Pharmacol 141:746–754
Maruyama W, Yi H, Takahashi T, Shimazu S, Ohde H et al (2004) Neuroprotective function of R-(-)-1-(benzofuran-2-yl)-2-propylaminopentane, [R-(-)-BPAP], against apoptosis induced by N-methyl(R)salsolinol, an endogenous dopaminergic neurotoxin, in human dopaminergic neuroblastoma SH-SY5Y cells. Life Sci 75:107–117
Morita M, Kumashiro R, Kubo N, Nakashima Y, Yoshida R et al (2010) Alcohol drinking, cigarette smoking, and the development of squamous cell carcinoma of the esophagus: epidemiology, clinical findings, and prevention. Int J Clin Oncol 15:126–134
Naoi M, Maruyama W, Nagy GM (2004) Dopamine-derived salsolinol derivatives as endogenous monoamine oxidase inhibitors: occurrence, metabolism and function in human brains. Neurotoxicology 25:193–204
Oliveira-da-Silva A, Vieira FB, Cristina-Rodrigues F, Filgueiras CC, Manhaes AC, Abreu-Villaca Y (2009) Increased apoptosis and reduced neuronal and glial densities in the hippocampus due to nicotine and ethanol exposure in adolescent mice. Int J Dev Neurosci 27:539–548
Oliveira-da-Silva A, Manhaes AC, Cristina-Rodrigues F, Filgueiras CC, Abreu-Villaca Y (2010) Hippocampal increased cell death and decreased cell density elicited by nicotine and/or ethanol during adolescence are reversed during drug withdrawal. Neuroscience 167:163–173
Picciotto MR, Zoli M (2008) Neuroprotection via nAChRs: the role of nAChRs in neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. Front Biosci 13:492–504
Quik M, O’Leary K, Tanner CM (2008) Nicotine and Parkinson’s disease: implications for therapy. Mov Disord 23:1641–1652
Rossini AR, Hashimoto CL, Iriya K, Zerbini C, Baba ER, Moraes-Filho JP (2008) Dietary habits, ethanol and tobacco consumption as predictive factors in the development of esophageal carcinoma in patients with head and neck neoplasms. Dis Esophagus 21:316–321
Smith AM, Zeve DR, Dohrman DP, Chen WJ (2006) The interactive effect of alcohol and nicotine on NGF-treated pheochromocytoma cells. Alcohol 39:65–72
Storch A, Ott S, Hwang YI, Ortmann R, Hein A et al (2002) Selective dopaminergic neurotoxicity of isoquinoline derivatives related to Parkinson’s disease: studies using heterologous expression systems of the dopamine transporter. Biochem Pharmacol 63:909–920
Tizabi Y, Al-Namaeh M, Manaye KF, Taylor RE (2003) Protective effects of nicotine on ethanol-induced toxicity in cultured cerebellar granule cells. Neurotox Res 5:315–321
Tizabi Y, Manaye KF, Smoot DT, Taylor RE (2004) Nicotine inhibits ethanol-induced toxicity in cultured cerebral cortical cells. Neurotox Res 6:311–316
Tizabi Y, Manaye KF, Taylor RE (2005) Nicotine blocks ethanol-induced apoptosis in primary cultures of rat cerebral cortical and cerebellar granule cells. Neurotox Res 7:319–322
Tønnesen P (2009) Smoking cessation: how compelling is the evidence? A review. Health Policy 91:S15–S25
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Supported by NIAAA (P20 AA014643), NIH/NIGMS (2 SO6 GM08016-39), and NIH-RCMI 2 G12 RR003048.
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Ramlochansingh, C., Taylor, R.E. & Tizabi, Y. Toxic Effects of Low Alcohol and Nicotine Combinations in SH-SY5Y Cells are Apoptotically Mediated. Neurotox Res 20, 263–269 (2011). https://doi.org/10.1007/s12640-011-9239-x
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DOI: https://doi.org/10.1007/s12640-011-9239-x