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Free Radic Biol Med. 2017 Jul;108:66-76. doi: 10.1016/j.freeradbiomed.2017.03.006. Epub 2017 Mar 12.

Protective effects of coffee against oxidative stress induced by the tobacco carcinogen benzo[α]pyrene.

Author information

1
Department of Internal Medicine I, University Hospital Bonn, 53127 Bonn, Germany. Electronic address: sandra.kalthoff@ukb.uni-bonn.de.
2
Department of Internal Medicine I, University Hospital Bonn, 53127 Bonn, Germany. Electronic address: steffen.landerer@ukb.uni-bonn.de.
3
Department of Internal Medicine I, University Hospital Bonn, 53127 Bonn, Germany. Electronic address: julia.reich@ukb.uni-bonn.de.
4
Department of Internal Medicine I, University Hospital Bonn, 53127 Bonn, Germany. Electronic address: christian.strassburg@ukb.uni-bonn.de.

Abstract

AIMS:

Coffee consumption has been epidemiologically associated with a lower risk for liver cirrhosis and cancer. UDP-glucuronosyltransferases (UGT1A) catalyze the detoxification of reactive metabolites thereby acting as indirect antioxidants. Aim of the study was to examine UGT1A regulation in response to Benzo[α]pyrene (BaP) to elucidate the potentially protective effects of coffee on BaP-induced oxidative stress and toxicity.

RESULTS:

In cell culture (HepG2, KYSE70 cells) and in htgUGT1A-WT mice, UGT1A transcription was activated by BaP, while it was reduced or absent htgUGT1A-SNP (containing 10 commonly occurring UGT1A-SNPs) mice. siRNA-mediated knockdown identified aryl hydrocarbon receptor (AhR) and nuclear factor erythroid2-related factor-2 (Nrf2) as mediators of BaP-induced UGT1A upregulation. Exposure to coffee led to a reduction of BaP-induced production of reactive oxygen species in vitro and in htgUGT1A-WT and -SNP mice. After UGT1A silencing by UGT1A-specific siRNA in cell culture, the coffee-mediated reduction of ROS production was significantly impaired compared to UGT1A expressing cells.

CONCLUSION:

A common UGT1A haplotype, prevalent in 9% (homozygous) of the White population, significantly impairs the expression of UGT1A enzymes in response to the putative tobacco carcinogen BaP and is likely to represent a significant risk factor for reduced detoxification and increased genotoxicity. Coffee was demonstrated to inhibit BaP-induced production of oxidative stress by UGT1A activation, and is therefore an attractive candidate for chemoprotection in risk groups for HCC or other tumors.

KEYWORDS:

BaP; Coffee; Glucuronidation; Oxidative stress

[Indexed for MEDLINE]

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