PMID- 34065697 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210615 IS - 2076-3921 (Print) IS - 2076-3921 (Electronic) IS - 2076-3921 (Linking) VI - 10 IP - 5 DP - 2021 May 16 TI - Quercetin and Isorhamnetin Attenuate Benzo[a]pyrene-Induced Toxicity by Modulating Detoxification Enzymes through the AhR and NRF2 Signaling Pathways. LID - 10.3390/antiox10050787 [doi] LID - 787 AB - 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. FAU - Kim, Min AU - Kim M AUID- ORCID: 0000-0001-7287-7002 AD - Department of Life Science, Dongguk University-Seoul, Biomedi Campus, 32 Dongguk-ro, Ilsandong-gu, Goyang 10326, Gyeonggi-do, Korea. FAU - Jee, Seung-Cheol AU - Jee SC AUID- ORCID: 0000-0002-9635-9362 AD - Department of Life Science, Dongguk University-Seoul, Biomedi Campus, 32 Dongguk-ro, Ilsandong-gu, Goyang 10326, Gyeonggi-do, Korea. FAU - Kim, Kyeong-Seok AU - Kim KS AD - Division of Toxicology, School of Pharmacy, Sungkyunkwan University-Suwon, Suwon 16419, Gyeonggi-do, Korea. FAU - Kim, Hyung-Sik AU - Kim HS AUID- ORCID: 0000-0001-7657-3970 AD - Division of Toxicology, School of Pharmacy, Sungkyunkwan University-Suwon, Suwon 16419, Gyeonggi-do, Korea. FAU - Yu, Kyoung-Nae AU - Yu KN AD - Department of Life Science, Dongguk University-Seoul, Biomedi Campus, 32 Dongguk-ro, Ilsandong-gu, Goyang 10326, Gyeonggi-do, Korea. FAU - Sung, Jung-Suk AU - Sung JS AD - Department of Life Science, Dongguk University-Seoul, Biomedi Campus, 32 Dongguk-ro, Ilsandong-gu, Goyang 10326, Gyeonggi-do, Korea. LA - eng GR - 14162KFDA072/Korea Food and Drug Administration/ GR - 2017001970003/Ministry of Environment of korea/ PT - Journal Article DEP - 20210516 PL - Switzerland TA - Antioxidants (Basel) JT - Antioxidants (Basel, Switzerland) JID - 101668981 PMC - PMC8156367 OTO - NOTNLM OT - AhR OT - NRF2 OT - benzo[a]pyrene OT - isorhamnetin OT - quercetin OT - xenobiotic metabolism COIS- The authors declare no conflict of interest. EDAT- 2021/06/03 06:00 MHDA- 2021/06/03 06:01 PMCR- 2021/05/16 CRDT- 2021/06/02 01:13 PHST- 2021/04/26 00:00 [received] PHST- 2021/05/13 00:00 [revised] PHST- 2021/05/14 00:00 [accepted] PHST- 2021/06/02 01:13 [entrez] PHST- 2021/06/03 06:00 [pubmed] PHST- 2021/06/03 06:01 [medline] PHST- 2021/05/16 00:00 [pmc-release] AID - antiox10050787 [pii] AID - antioxidants-10-00787 [pii] AID - 10.3390/antiox10050787 [doi] PST - epublish SO - Antioxidants (Basel). 2021 May 16;10(5):787. doi: 10.3390/antiox10050787.