AUTHOR=Vivarelli Fabio , Morosini Camilla , Rullo Laura , Losapio Loredana Maria , Lacorte Antonio , Sangiorgi Stefano , Ghini Severino , Fagiolino Ivan , Franchi Paola , Lucarini Marco , Candeletti Sanzio , Canistro Donatella , Romualdi Patrizia , Paolini Moreno 

TITLE=Effects of unburned tobacco smoke on inflammatory and oxidative mediators in the rat prefrontal cortex

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 15 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1328917

DOI=10.3389/fphar.2024.1328917

ISSN=1663-9812

ABSTRACT=Although the Food and Drug Administration has authorized the marketing of "Heat-not-Burn" electronic cigarettes (HnB) as a Modified Risk Tobacco Product (MRTP), toxicological effects of HnB smoke exposure on the brain are still unexplored. Here, paramagnetic resonance of the prefrontal cortex  (PFC) of HnB exposed rats show a powerful increase in reactive radical species (RRS) yield coupled with an inflammatory response mediated by NF-κB-target genes including TNF-α, IL-1β, IL-6 and the down-regulation of peroxisome proliferator-activated receptor (PPAR) alfa and gamma expression.PFC shows higher levels of 8-hydroxyguanosine as a marker of DNA oxidative damage along with the activation of antioxidant machinery and DNA repair systems, including Xeroderma Pigmentosus group C protein complex (XPC) and 8-oxoguanine DNA glycosylase-1. HnB also induces the expression of drug-metabolizing enzymes such as CYP1A1, CYP2A6, CYP2B6, CYP2E, mainly involved in the biotrasformation of nicotine and several carcinogenic agents such as aldehydes and polycyclic aromatic hydrocarbons here recorded in the HnB stick smoke. Taken together, these effects, from disruption of redox homeostasis, inflammation, PPAR manipulation along with enhanced bioactivation of neurotoxicants, up-regulation of cMYC protooncogene to impairment of primary cellular defence mechanisms, suggest a possible increased risk of brain cancer. Although HnB device reduces the emission of tobacco toxicants, our findings indicate that its consumption may carry a risk of potential adverse health effects, especially in non-smokers so far. Further studies are needed to fully understand the long-term effects of these devices.