β-carotene and retinol reduce benzo[a]pyrene-induced mutagenicity and oxidative stress via transcriptional modulation of xenobiotic metabolizing enzymes in human HepG2 cell line

Abstract

Benzo[a]pyrene (B[a]P) is one of the polycyclic aromatic hydrocarbons which is formed due to smoking of foods, incomplete combustion of woods, vehicle exhausts, and cigarettes smokes. B[a]P gets entry into human and animal bodies mainly through their diets. Metabolic activation of B[a]P is required to induce mutagenesis and carcinogenesis in animal and human studies. Carotenoids and retinoids are phytochemicals that if ingested have multiple physiological interferences in the human and animal bodies. In this study, we firstly investigated the protective effects of β-carotene, β-apo-8-carotenal, retinol, and retinoic acid against B[a]P-induced mutagenicity and oxidative stress in human HepG2 cells. Secondly, we tested the hypothesis of modulating xenobiotic metabolizing enzymes (XMEs) by carotenoids and retinoids as a possible mechanism of protection by these micronutrients against B[a]P adverse effects. The obtained results declared that β-carotene and retinol significantly reduced B[a]P-induced mutagenicity and oxidative stress. Tested carotenoids and retinoids reduced B[a]P-induced phase I XMEs and induced B[a]P reduced phase II and III XMEs. Thus, the protective effects of these micronutrients are probably due to their ability of induction of phase II and III enzymes and interference with the induction of phase I enzymes by the promutagen, B[a]P. It is highly recommended to consume foods rich in these micronutrients in the areas of high PAH pollution.

Effects of Pyrene on Human Liver HepG2 Cells: Cytotoxicity, Oxidative Stress, and Transcriptomic Changes in Xenobiotic Metabolizing Enzymes and Inflammatory Markers with Protection Trial Using Lycopene

“…The achieved results indicated that pyrene had significant cytotoxic effects on HepG2 cells at 50 n causing 28% reduction in cell viability. Unlikely, benzo[a]pyrene, a promutagenic PAH, did not alter HepG2 cell viability [8, 15]. Pyrene caused a clear induction of oxidative damage, in terms of the production of ROS, in a concentration-dependent manner (Figure 1).…”

“…Each experiment was represented by 6 plates/treatments. Primer sets for the selected targets were designed based on previous work [8] and are presented in Table 1.…”

“…Air regulates phase I enzymes such as cytochrome P450 (CYP) 1A1 and 1A2, phase II enzymes such as uridine diphosphate glucuronosyltransferase (UGT) 1A6, and NAD(P) quinone oxidoreductase 1 (NQO1) [7]. Several reports investigated the toxic and mutagenic effects of benzo[a]pyrene as a major promutagenic and procarcinogenic PAH in the human liver and colon cell lines [1, 8]. However, pyrene-induced adverse effects including cytotoxicity and oxidative stress and the mechanisms behind such effects are scarcely investigated.…”

Health risk in transport workers. Part II. Dietary compounds as modulators of occupational exposure to chemicals

“…Apart from the studies aiming at analyzing the influence of individual products with a specific content on the cascade of changes induced by BaP, there are many papers describing the influence of isolated single compounds, such as vitamin C, β-carotenoids, retinol, retinoic acid, phenethyl isothiocyanate, luteolin, chrysin, naringenin, quercetin, damnacanthal, proanthocyanidine, resveratrol, berberine, catechin, anthocyanins, apigenin or kaempferol. The mechanisms of action of the selected phytochemicals and the above-mentioned dietary compounds are presented in Table 1 [52][53][54][55][56][57][59][60][61][62][63][64][65][66][67][68][69][70][71][72][73].…”

A biochemical approach to the anti-inflammatory, antioxidant and antiapoptotic potential of beta-carotene as a protective agent against bromobenzene-induced hepatotoxicity in female Wistar albino rats

“…Amelioration of cardiotoxicity was observed in rats on treatment with beta-carotene (Bahadır et al, 2018). It was recommended to consume food rich in beta-carotene and retinol in areas highly polluted with polycyclic aromatic hydrocarbons (Darwish et al, 2018). However, avoiding oxidant sources such as cigarette smoke and alcohol must be considered when taking dietary antioxidants (Liu et al, 2018).…”