ALCOHOL AND CARBON NANOPARTICLES EXACERBATE NICOTINE NEUROTOXICITY

Our previous studies show that nicotine exposure for 1 week significantly increases blood-brain barrier (BBB) breakdown to proetins and induces brain edema and neuronal damages in adult rats. Since nicotine smoking is often associated with tar inhalation, it would be interesting to explore the effects of carbon nanoparticles (NPs) on brain damage in our model. Furthermore, nicotine consumption is often associated with alcohol intake we also examined the combined effects of alcohol and nicotine on brain pathology. Rats were treated with nicotine (9 mg/kg/day, s.c.) at room temperature (21±1°C) for 1 week. In separate group of animals, co-administration nicotine and Ethyl alcohol (EtOH, 1.5 g/kg, i.p./day) or carbon NPs (single wall carbon nanotube SWCNT, 10 mg/kg/day, i.p.) was done for 1 week. On the 8th day the BBB permeability to protein tracers (Evans blue albumin, EBA 3 ml/kg, i.v. and [131]-I-Na 100 µCi/kg, i.v.), brain edema (water content) and brain pathology (neuronal damage using Nissl or H&E on paraffin sections) were evaluated in all the groups in a blinded fashion. Our results show that a combination of nicotine and alcohol exacerbated BBB leakage (EBA by 240 % and radioiodine 300 %), brain edema (water content +1.5 %, volume swelling % ƒ 6%) and neuronal injury in the cerebral cortex (120 %) and hippocampus (190%) from nicotine alone. Interestingly, the combination of nicotine and SWCNT resulted in only 50 to 90% increase in brain pathology, BBB breakdown and edema formation as compared to nicotine alone. These observations show that the neurotoxicity of nicotine is exacerbated with consumption of alcohol or carbon nanoparticles. It remains to be seen whether a combination of nicotine, alcohol and tar could have further additive effects on brain damage and neuroprotective effects of drugs, e.g., cerebrolysin will reduce brain pathology.