Toxicological aspects associated with Electronic Nicotine Delivery System (ENDS) consumption

Tobacco smoking remains a leading cause of premature death worldwide. In combination with conventional smoking cessation protocols, Electronic Nicotine Delivery Systems (ENDS) (including the e-cigarette and the newest heat-not-burn devices) have been proposed as a useful smoking cessation tool. Although the levels of toxicants in the mainstream are significantly lower than those observed in tobacco smoke, our research team raised some concerns about the alleged health risk associated with their use. Our studies show the co-mutagenic and cancer-initiating effects of ENDS exposure in rat lung. We found that ENDS produce extensive DNA damage in leukocytes measured by the comet assay as well as increased rate of micronuclei formation in reticulocytes. Furthermore, electron microscopy images indicate severe remodeling of the smaller and larger airways. ENDS exposure increases oxidative stress in the prefrontal cortex with an increased level of 8-hydroxyguanosine, a reliable marker of DNA oxidation positively associated with smoking habit. Consistently, xeroderma pigmentosum group C protein complex and 8-oxoguanine DNA glycosylase-1 (OGG-1), two crucial proteins involved in major DNA repair pathways were found upregulated in exposed animals. ENDS can induce neuroinflammation through activation of the NF-κB signaling pathway and the down-regulation of PPARα and PPARγ as negative regulators of inflammation. Interestingly, ENDS affect male gonadal function by increasing markers of oxidative stress including those associated with DNA damage, as well as NF-kB dependent pro-inflammatory mediators; inactivation of key androgenic enzymes such as 3β-hydroxysteroid dehydrogenase (3β-HSD) and 17β-hydroxysteroid dehydrogenase (17β-HSD), together with reduced testosterone synthesis suggest, potential impairment of male gonadal function. Collectively, our findings reveal that ENDS consumption mimics some pathological mechanisms typically triggered by conventional cigarettes suggesting caution in proposing them as a healthy alternative to smoking or as an aid to smoking cessation especially in young people and pregnant women