Aryl Hydrocarbon and Constitutive Androstane Receptors are Compulsory Determinants in the Induction of Cytochrome P450 1A2, 2A6, and 2A13 Expression by Nicotine and N-Nitrosodiethanolamine in HepG2 Cells

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Published: Aug 16, 2019
DOI: https://doi.org/10.14456/ijps.2019.39
Keywords:
Nicotine Nitrosamine Cytochrome P450 AhR PXR CAR

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Nawaratt
Graduate Student (Master of Pharmacy in Pharmaceuticals), Research Group for Pharmaceutical Activities of Natural Products using Pharmaceutical Biotechnology (PANPB), Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002
Waranya Chatuphonprasert
Faculty of Medicine, Mahasarakham University, Mahasarakham 44000 Thailand
Kanokwan Jarukamjorn
Ph.D. (Pharmaceutical Sciences), Research Group for Pharmaceutical Activities of Natural Products using Pharmaceutical Biotechnology (PANPB), Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002

Abstract

Introduction: Nicotine and N-nitrosodiethanolamine (NDELA) are hepatotoxic and hepatocarcinogenic substances in human and animals. Cytochrome P450 (CYPs) 1A and 2A mainly metabolize nicotine and nitrosamines in the liver but knowledge about their regulatory pathway is still limited. The current study aimed to examine the effects of nicotine and NDELA on regulatory expressions of CYPs and nuclear receptors, aryl hydrocarbon receptor (AhR), pregnane X receptor (PXR), and constitutive androstane receptor (CAR) mRNA in human hepatocellular carcinoma cells (HepG2). Materials and method: HepG2 cells (5x105 cells per well) were cultured in DMEM supplemented with 10% FBS. The cells were treated with nicotine or NDELA (1, 10, and 100 μM) for 24 h, compared to control (non-treatment) or 0.1% ethanol (EtOH) which was used as the solvent of nicotine and NDELA. Total RNAs were extracted and the mRNA expression of each gene was determined by RT-qPCR. Results: Both of nicotine and NDLEA at 100 μM significantly up-regulated expression of CYP1A2, CYP2A6, and CYP2A13 mRNA. Furthermore, nicotine and NDELA significantly induced the expression of AhR and CAR mRNA. Interestingly, nicotine induced PXR mRNA whereas NDELA did not. Conclusion: AhR and CAR might be compulsory determinants for regulation of CYP1A2 and CYP2A6/13 expression by nicotine and NDELA. However, different regulation of PXR by nicotine and NDELA is of interest for further study.

Article Details

Issue
Vol. 15 No. 3 (2019): Volume 15 No.3, July – September 2019
Section
Pharmaceutical Sciences

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