MON-162 Hepatic DNA Damage Induced by ENDS Is Associated with Decreased Levels of NAD+

Electronic nicotine delivery systems (ENDS) or electronic cigarettes (e-cigs) are becoming exceptionally popular in the world as an alternative to conventional nicotine cigarettes, both in smokers and people who have never smoked. Use of tobacco products is a major risk factor for diabetes and contribute to non-alcoholic fatty liver disease (NAFLD). Nicotinamide adenine dinucleotide (NAD+) plays a critical role in regulating metabolism and aging. Our laboratory has shown that ENDS induces lipolysis and NAFLD in Apolipoprotein E Knockout (ApoE(-/-)). We developed an ENDS exposure model that delivers nicotine in a manner similar to that of human ENDS users. ApoE(-/-) mice were exposed to saline, ENDS without nicotine [ENDS (0%)] and ENDS with 2.4% nicotine [(ENDS (2.4%)] aerosol for 12 weeks. Mice exposed to ENDS (2.4%) had increased apurinic/apyrimidinic (AP) sites (a manifestation of DNA damage) associated with a decreased NAD+/NADH ratio in the liver, in comparison with saline and ENDS (0%). Western blot analysis shows that mice treated with ENDS (2.4%) had increased poly(ADP-ribose) polymerases 1 (PARP-1) activity associated with reduced levels of Sirtuin 1 (SIRT1). Furthermore, hepatic oxidative stress and mitochondrial DNA mutations were increased in mice treated with ENDS (2.4%). These results demonstrate adverse effects of ENDS leading to NAD+ deficiency which is a common central pathological factor of a number of metabolic- and aging-associated diseases.