The Impact of Tobacco Cigarettes, Vaping Products and Tobacco Heating Products on Oxidative Stress

Abstract

Cells constantly produce oxidizing species because of their metabolic activity, which is counteracted by the continuous production of antioxidant species to maintain the homeostasis of the redox balance. A deviation from the metabolic steady state leads to a condition of oxidative stress. The source of oxidative species can be endogenous or exogenous. A major exogenous source of these species is tobacco smoking. Oxidative damage can be induced in cells by chemical species contained in smoke through the generation of pro-inflammatory compounds and the modulation of intracellular pro-inflammatory pathways, resulting in a pathological condition. Cessation of smoking reduces the morbidity and mortality associated with cigarette use. Next-generation products (NGPs), as alternatives to combustible cigarettes, such as electronic cigarettes (e-cig) and tobacco heating products (THPs), have been proposed as a harm reduction strategy to reduce the deleterious impacts of cigarette smoking. In this review, we examine the impact of tobacco smoke and MRPs on oxidative stress in different pathologies, including respiratory and cardiovascular diseases and tumors. The impact of tobacco cigarette smoke on oxidative stress signaling in human health is well established, whereas the safety profile of MRPs seems to be higher than tobacco cigarettes, but further, well-conceived, studies are needed to better understand the oxidative effects of these products with long-term exposure.

Keywords: airway diseases; cigarette; harm reduction; oxidative stress; tobacco.

Figure 1

Endogenous sources of oxidants. Cellular ROS and RNS can be generated from different metabolic reactions, including mitochondrial electron transport and inflammation processes. Under physiological conditions, 0.2–2% of the electrons in the mitochondrial electron transport escape from the transport and interact with oxygen to produce superoxide (O₂^•−) or hydrogen peroxide (H₂O₂). Moreover, inflammatory processes contribute to the increase in ROS/RNS by the activation of numerous pro-oxidant enzymatic systems, such as NADPH oxidase (NOX), xanthine oxidase (XO), myeloperoxidase (MPO), and nitric oxide synthase (NOS). However, the presence of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX), contributes to maintaining the biological redox homeostasis.

Figure 2

Chemical compounds generated by cigarette smoke and next-generation products (NGPs). Tobacco smoke is a complex mixture of thousands of different harmful and potentially harmful chemical species, including toxicants, carcinogens, and organic compounds (left panel). Aerosols generated by NGPs also contain harmful and potentially harmful compounds produced through the thermal decomposition of the solvents, but their quantity is generally lower compared to the ones found in cigarette smoke.

Figure 3

Generation of inflammatory response in the lung. Cigarette smoke induces cytotoxicity in the airway, promoting the persistence of activated pro-inflammatory cells (neutrophils, eosinophils, and macrophages) and their endogenous production of reactive oxygen species (ROS). The aerosols of next-generation products (NGPs) seem to display lower cytotoxicity than cigarette smoke. However, chemicals generated from NGPs could promote the activation of inflammatory cells, although the literature data are conflicting to date. Black cells = necrotic cells; cells with brown nuclei = damaged cells; cells with pink nuclei = normal cells; O₂^•− = superoxide anion; H₂O₂ = hydrogen peroxide; HOBr = hypobromous acid; HOCl = hypochlorous acid; NO = nitric oxide; RSN = reactive nitrogen species; ^•OH = hydroxyl radical; Fe²⁺ = ferrous ion; NOX = NADPH oxidase; SOD = superoxide dismutase; GPX = glutathione peroxidase; CAT = catalase; iNOS = inducible nitric oxide synthase.

Figure 4

Mechanisms inducing endothelial dysfunction through reduced NO bioactivity.

Figure 5

The role of reactive oxygen species (ROS) in the development of cancer. The increase in ROS in normal cells triggers stress responses and DNA repair to repair the ROS-mediated damage to genetic materials. However, the exposure to high levels of oxidants and the consequential redox imbalance lead to DNA damage, including base mismatch, single-strand break, or double-strand break. Moreover, ROS induce DNA mutations that could cause a loss of p53 function and DNA repair disfunction, leading to genomic instability, which further leads to the activation of oncogenes, aberrant metabolic stress, mitochondrial dysfunction, and a decrease in antioxidants. All these events activate a vicious cycle that amplifies oxidative stress and promotes cancer development.