Toxic Effects of Low Alcohol and Nicotine Combinations in SH-SY5Y Cells are Apoptotically Mediated

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 salsolinolinduced 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.

PACAP Protects Against Ethanol and Nicotine Toxicity in SH-SY5Y Cells: Implications for Drinking-Smoking Co-morbidity

“…Nicotine/nicotinic agonists have been suggested to have therapeutic potential in neuropsychiatric and neurodegenerative diseases, particularly in Parkinson's disease (PD) (Quik et al 2015;Tizabi 2016;Tizabi and Getachew 2017). We had also observed protective effects of low nicotine concentration (e.g., 10 μM) against salsolinol-induced toxicity in SH-SY5Y cells (Copeland et al 2007;Ramlochansingh et al 2011). Curiously, however, when we combined low alcohol with low nicotine concentrations, contrary to our expectation of an additive protective effect, a significant toxicity, with or without salsolinol, was noted (Ramlochansingh et al 2011).…”

“…We had also observed protective effects of low nicotine concentration (e.g., 10 μM) against salsolinol-induced toxicity in SH-SY5Y cells (Copeland et al 2007;Ramlochansingh et al 2011). Curiously, however, when we combined low alcohol with low nicotine concentrations, contrary to our expectation of an additive protective effect, a significant toxicity, with or without salsolinol, was noted (Ramlochansingh et al 2011).…”

“…Indeed, protective effects of low alcohol concentration (e.g., 10 mM) against salsolinol-induced toxicity in neuroblastoma-derived SH-SY5Y cells, a commonly used cell culture model of substantia nigra (SN) dopaminergic cells, were reported (Ramlochansingh et al 2011). Salsolinol is an endogenous compound that is derived from condensation of dopamine and aldehydes and in high levels can be selectively toxic to SN neurons (Qualls et al 2014;Możdżeń et al 2015).…”

“…Values are mean ± SEM. Each experiment was carried out two times and each time in quadruplicate alcohol and nicotine, in low concentrations as used in this study, have been shown to have protective effects against various toxic agents when used alone (Ramlochansingh et al 2011;Tizabi 2016). Indeed, it has been shown that low ethanol concentration can have variety of beneficial effects, including neuroprotection (Casañas-Sánchez et al 2016).…”

Duality of Antidepressants and Neuroprotectants

“…Moreover, in vitro and in vivo studies have shown that nicotine may protect against nigrostriatal damage induced by various compounds. Thus, in Parkinson’s disease cell models, nicotine protects against endogenous substances such as salsolinol and aminochrome that selectively damage dopaminergic cells (Copeland et al 2005, 2007; Das and Tizabi 2009; Ramlochansingh et al 2011; Munoz et al 2012). Similarly in animal studies, including non-human primates, it has been shown that nicotine delays Parkinson’s disease-like symptoms induced by MPTP (Quik et al 2006, 2009, 2014).…”