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© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Benzo[a]pyrene, classified as a Group 1 carcinogen, is metabolized to B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE), causing DNA mutations and eventually cancer. Quercetin is a dietary flavonoid abundant in fruits and vegetables. After quercetin intake, quercetin’s metabolites isorhamnetin and miquelianin are more highly concentrated than quercetin in the human plasma. In this study, we investigated the molecular mechanisms associated with the cytoprotective effect of quercetin and its metabolites against benzo[a]pyrene from a detoxification perspective. Quercetin and its metabolite isorhamnetin reduced benzo[a]pyrene-induced cytotoxicity, whereas the metabolite miquelianin did not mitigate benzo[a]pyrene-induced cytotoxicity. Moreover, quercetin and isorhamnetin reduced intracellular levels of BPDE-DNA adducts. The formation and elimination of BPDE is mediated by the xenobiotic detoxification process. Quercetin and isorhamnetin increased the gene and protein expression levels of phase I, II, and III enzymes involved in xenobiotic detoxification. Furthermore, quercetin and isorhamnetin induced the translocation of aryl hydrocarbon receptor (AhR) and nuclear factor erythroid 2-related factor 2 (NRF2), which regulate the expression level of phase enzymes. Our results suggest that quercetin and isorhamnetin promote the metabolism, detoxification, and elimination of B[a]P, thereby increasing anti-genotoxic effects and protecting against B[a]P-induced cytotoxicity.

Details

Title
Quercetin and Isorhamnetin Attenuate Benzo[a]pyrene-Induced Toxicity by Modulating Detoxification Enzymes through the AhR and NRF2 Signaling Pathways
Author
Kim, Min 1   VIAFID ORCID Logo  ; Seung-Cheol Jee 1   VIAFID ORCID Logo  ; Kim, Kyeong-Seok 2 ; Hyung-Sik, Kim 2   VIAFID ORCID Logo  ; Kyoung-Nae Yu 1 ; Jung-Suk, Sung 1 

 Department of Life Science, Dongguk University-Seoul, Biomedi Campus, 32 Dongguk-ro, Ilsandong-gu, Goyang 10326, Gyeonggi-do, Korea; [email protected] (M.K.); [email protected] (S.-C.J.); [email protected] (K.-N.Y.) 
 Division of Toxicology, School of Pharmacy, Sungkyunkwan University-Suwon, Suwon 16419, Gyeonggi-do, Korea; [email protected] (K.-S.K.); [email protected] (H.-S.K.) 
First page
787
Publication year
2021
Publication date
2021
Publisher
MDPI AG
e-ISSN
20763921
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2531377941
Copyright
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.