Journal Article

Comparative evaluation of cigarette smoke and a heated tobacco product on microglial toxicity, oxidative stress and inflammatory response

Orlando, Laura, Denaro, Simona, Partsinevelos, Konstantinos, Alanazi, Amer M., Tomasello, Barbara, Li Volti, Giovanni, Amorini, Angela Maria, Longhitano, Lucia, Giordano, Antonio, Caruso, Massimo, Vicario, Nunzio, Sun, Ang, Emma, Rosalia, Distefano, Alfio

2024

Overview

Background Tobacco smoking is the leading cause of preventable death and disease worldwide, with over 8 million annual deaths attributed to cigarette smoking. This study investigates the impact of cigarette smoke and heated tobacco products (HTPs) on microglial function, focusing on toxicological profiles, inflammatory responses, and oxidative stress using ISO standard and clinically relevant conditions of exposure. Methods We assessed cell viability, reactive oxygen species (ROS) production, lipid peroxidation, mitochondrial function, unfolded protein response, and inflammation in human microglial cells (HMC3) exposed to cigarette smoke, HTP aerosol or nicotine. Results Our findings show that cigarette smoke significantly reduces microglial viability, increases ROS formation, induces lipid peroxidation, and reduces intracellular glutathione levels. Cigarette smoke also alters the expression of genes involved in mitochondrial dynamics and biogenesis, leading to mitochondrial dysfunction. Additionally, cigarette smoke impairs the unfolded protein response, activates the NF-κB pathway, and induces a pro-inflammatory state characterized by increased TNF and IL-18 expression. Furthermore, cigarette smoke causes DNA damage and decreases the expression of the aging marker Klotho β. In contrast, HTP, exhibited a lesser degree of microglial toxicity, with reduced ROS production, lipid peroxidation, and mitochondrial dysfunction compared to conventional cigarettes. Conclusion These results highlight the differential toxicological profile of cigarette smoke and HTP on microglial cells, suggesting a potential harm reduction strategy for neurodegenerative disease for smokers unwilling or unable to quit.

• Publisher: BioMed Central,BioMed Central Ltd,BMC
• Subject: B cells / Biomedical and Life Sciences / Biomedicine / Cell Line / Cell Survival - drug effects / Cigarette smoke / Cigarette smoking / Comparative analysis / Degeneration / DNA Damage / Ethylenediaminetetraacetic acid / Genes / Health aspects / Heated tobacco product / Hot Temperature / Humans / Inflammation / Inflammation - pathology / Lipid peroxidation / Lipid Peroxidation - drug effects / Medicine/Public Health / Microglia / Microglia - drug effects / Microglia - metabolism / Microglia - pathology / Mitochondria - drug effects / Mitochondria - metabolism / Nervous system / Nervous system diseases / NF-kappa B - metabolism / Nicotine / Oxidative stress / Oxidative Stress - drug effects / Physiological aspects / Reactive Oxygen Species - metabolism / Smoke - adverse effects / Smoking / Tobacco Products - adverse effects / Toxicity / Translational Signaling and System Biology / Unfolded Protein Response - drug effects