Cigarette smoke, nicotine and cotinine protect against 6-hydroxydopamine-induced toxicity in SH-SY5Y cells.

Epidemiological studies consistently demonstrate a reduced incidence of Parkinson's disease in smokers. As an approach to evaluate whether nicotine in tobacco may be involved in this apparent protective effect, we compared the effect of mainstream 1R4F cigarette smoke solutions, which contain chemicals inhaled by active smokers, and nicotine against 6-hydroxydopamine (6-OHDA)-induced toxicity in an in vitro cell culture system. For this purpose we used terminally differentiated SH-SY5Y neuroblastoma cells that exhibit a catecholaminergic phenotype and express nicotinic receptors. Cells were pre-incubated for 24 h in mainstream-cigarette smoke solutions (0.06, 0.2, or 0.6 cigarette puffs/ml) made from University of Kentucky 1R4F research brand cigarettes, followed by the addition of 6-OHDA for another 24-48 h. The 0.2, but not 0.06, puffs/ml dose, significantly protected against 6-OHDA-induced toxicity in SH-SY5Y cells. This dose yielded final nicotine concentrations of approximately 5 x 10(-7) M, which is similar to plasma smoking levels. Although the 0.6 puffs/ml dose caused significant toxicity on its own, it also appeared to protect against 6-OHDA-induced damage. We next tested the effect of nicotine, as well as its metabolite cotinine. These agents protected against the toxic effects of 6-OHDA in SH-SY5Y cells at concentrations ranging from 10(-7) to 10(-5) M. These combined results support the idea that nicotine is one of the components in cigarette smoke that has a protective effect against neurotoxic insults. These data suggest that nicotine may be of potential therapeutic value for Parkinson's disease.