Molecular Mechanisms of Action of Selected Substances Involved in the Reduction of Benzo[a]pyrene-Induced Oxidative Stress

Abstract

Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon (PAH) primarily formed by burning of fossil fuels, wood and other organic materials. BaP as group I carcinogen shows mutagenic and carcinogenic effects. One of the important mechanisms of action of (BaP) is its free radical activity, the effect of which is the induction of oxidative stress in cells. BaP induces oxidative stress through the production of reactive oxygen species (ROS), disturbances of the activity of antioxidant enzymes, and the reduction of the level of non-enzymatic antioxidants as well as of cytokine production. Chemical compounds, such as vitamin E, curcumin, quercetin, catechin, cyanidin, kuromanin, berberine, resveratrol, baicalein, myricetin, catechin hydrate, hesperetin, rhaponticin, as well as taurine, atorvastatin, diallyl sulfide, and those contained in green and white tea, lower the oxidative stress induced by BaP. They regulate the expression of genes involved in oxidative stress and inflammation, and therefore can reduce the level of ROS. These substances remove ROS and reduce the level of lipid and protein peroxidation, reduce formation of adducts with DNA, increase the level of enzymatic and non-enzymatic antioxidants and reduce the level of pro-inflammatory cytokines. BaP can undergo chemical modification in the living cells, which results in more reactive metabolites formation. Some of protective substances have the ability to reduce BaP metabolism, and in particular reduce the induction of cytochrome (CYP P450), which reduces the formation of oxidative metabolites, and therefore decreases ROS production. The aim of this review is to discuss the oxidative properties of BaP, and describe protective activities of selected chemicals against BaP activity based on of the latest publications.

Benzo[a]pyrene—Environmental Occurrence, Human Exposure, and Mechanisms of Toxicity

“…B[ a ]P also decreases the level of reduced glutathione (GSH), vitamin C, and vitamin E, as well as increases the level of lipid peroxidation and protein carbonyl formation, as well as increases the expression of CYP1A1 and proinflammatory cytokines. Metabolites of B[ a ]P (mainly BPDE) and ROS created during transformation of B[ a ]P are the most important contributors to the oxidative effects provoked by this substance [ 102 , 103 , 104 , 105 , 106 ] ( Figure 5 ).…”

“…Bukowska and Duchnowicz [ 103 ] described in their review that B[ a ]P can increase AhR translocation and, as a consequence, increases levels of CYP450 and other proteins involved in B[ a ]P metabolism. As the result, increased BPDA-DNA adduct levels and other DNA damage can occur.…”

“…Moreover, B[ a ]P has been reported to increase gene expression associated with inflammation and oxidative stress, as well as to deplete the expression and the activities of antioxidative enzymes, i.e., CAT, GPx, SOD, GST, and GR. Furthermore, B[ a ]P depleted nonenzymatic antioxidants levels, including GSH, Vit C, and Vit E. Metabolites of B[ a ]P (mainly BPDE) have been shown to induce ROS formation, as well as cause lipid peroxidation and protein carbonylation ( Figure 6 ) [ 102 , 103 , 104 , 105 ].…”

Mouse Models for Immune Checkpoint Blockade Therapeutic Research in Oral Cancer

“…GTX carcinogens can be said to be the initiator of cancer. For example, benzo(a)pyrene (BaP), a tobacco-related carcinogen, can form bulky BaP-DNA adducts and basic sites or, by reactive oxygen species (ROS) and metabolites generated during metabolism, causes DNA damage [ 82 , 83 ]. In contrast, NGTX carcinogens do not directly bind to DNA but affect the cell cycle, cause chronic inflammation [ 84 ], activate steroid hormone receptors (SHRs) to activate silent genetic pathways and generate reactive oxygen species (ROS), or cause immunosuppression [ 85 ].…”

Vanillic acid attenuates cell proliferation, xenobiotic enzyme activity, and the status of pulmonary mitochondrial enzymes in lung carcinoma

“…Free radical and non‐radical oxidizing species are commonly formed in animals exposed to carcinogens, and accumulating data shows that oxidative stress mediated by free radicals and electrophiles plays a key role in all phases of chemical carcinogenesis and tumorigenesis (Sharifi‐Rad et al, 2020). Benzo(a)pyrene, a well‐known lung carcinogen found in tobacco smoke, is known to generate massive numbers of free radicals, which then react with lipids, resulting in the production of lipid peroxides and the involvement of free radicals in B(a)P‐induced lung carcinogenesis (Bukowska & Duchnowicz, 2022). Inflammatory cells and their secretary growth factor govern many cellular activities such as cellular proliferation and differentiation, which are induced by harmful chemical exposure, which changes the risk of neoplasm either directly or indirectly (Gao et al, 2019).…”