Constitutive Effects of Lead on Aryl Hydrocarbon Receptor Gene Battery and Protection by β‐carotene and Ascorbic Acid in Human HepG2 Cells

Abstract

Lead (Pb) is an environmental pollutant that can get entry into human body through contaminated foods, drinks, and inhaled air leading to severe biological consequences, and has been responsible for many deaths worldwide. The objectives of this study were 1st to investigate the modulatory effects of environmentally relevant concentrations of Pb on AhR gene battery, which is controlling xenobiotics metabolism. 2nd, trials to reduce Pb‐induced adverse effects were done using some phytochemicals like β‐carotene or ascorbic acid. Human hepatoma (HepG2) cell lines were exposed to a wide range of Pb concentrations varying from physiological to toxic levels (0 to 10 mg/L) for 24 h. High Pb concentrations (1 to 10 mg/L) significantly reduced phase I (CYP1A1 and 1A2) and phase II (UGT1A6 and NQO1) xenobiotic metabolizing enzyme mRNA expression in a mechanistic manner through the AhR regulation pathway. Additionally, these Pb concentrations induced oxidative stress in HepG2 cells in terms of production of reactive oxygen species (ROS) and induced heme oxygenase‐1 mRNA expression in a concentration‐dependent phenomenon. Coexposure of HepG2 cells to physiological concentrations of some micronutrients, like β‐carotene (10 μM) or ascorbic acid (0.1 mM), along with Pb (1 mg/L) for 24 h significantly reduced the levels of ROS production and recovered AhR mRNA expression into the normal levels. Thus, consumption of foods rich in these micronutrients may help to reduce the adverse effects of lead in areas with high levels of pollution.

The Effects of Chronic Lifelong Activation of the AHR Pathway by Industrial Chemical Pollutants on Female Human Reproduction

“…On the contrary, higher Pb concentrations significantly reduced AHR expression. This suggests that the modulatory effects of Pb on AHR-mediated genes are possibly due to Pb-AHR crosstalk [ 29 ].…”

“…Several studies support, at least in part, our data. Pillai et al [ 28 ] and Nampoothiri et al [ 29 ] report that treatment of both lead and cadmium alone and in combination in a animal model decrease serum levels of estradiol and progesterone and this may be attributed to the inhibition of ovarian steroidogenic enzyme activity. Moreover, the decreased levels of ovarian steroids in metal-treated animals were also correlated with decreased numbers of follicles and the granulose cell population in the developing follicles.…”

Selective cytotoxic activity and protective effects of sodium ascorbate against hepatocellular carcinoma through its effect on oxidative stress and apoptosis in vivo and in vitro

“…A 96-well plate containing HepG2 cells (1 × 10 4 ) were incubated in a humidified CO 2 incubator at 37°C for 24 h. Cells were treated with both sodium ascorbate and cisplatin (50, 100 and 250 µM) and kept in humidified CO 2 incubator for 48 h. The viability was assessed using MTT (Sigma Aldrich Chemicals Co., St Louise, MO, USA) as described previously [12,16,23,24]. While, time course and doses of sodium ascorbate and cisplatin were in the range of previous studies [12,25,26].…”

Cardioprotective effects of omega‐3 fatty acids and ascorbic acid improve regenerative capacity of embryonic stem cell‐derived cardiac lineage cells

“…AA regenerates vitamin E and inhibits peroxidation of polyunsaturated fatty acids . AA induces the expression of antioxidant enzymes such as HO‐1 . However, it remained to be elucidated whether preincubation of cells with omega‐3 fatty acids or/and AA confer a cardiac cell therapeutic efficacy against MI.…”