Quercetin and Isorhamnetin Attenuate Benzo[a]pyrene-Induced Toxicity by Modulating Detoxification Enzymes through the AhR and NRF2 Signaling Pathways.
Min KimSeung-Cheol JeeKyeong-Seok KimHyung-Sik KimKyoung-Nae YuJung-Suk SungPublished in: Antioxidants (Basel, Switzerland) (2021)
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.
Keyphrases
- high glucose
- diabetic rats
- oxidative stress
- nuclear factor
- signaling pathway
- drug induced
- gene expression
- squamous cell carcinoma
- ms ms
- poor prognosis
- immune response
- risk assessment
- endothelial cells
- circulating tumor
- epithelial mesenchymal transition
- young adults
- climate change
- high resolution
- circulating tumor cells
- papillary thyroid
- nucleic acid
- endoplasmic reticulum stress
- long non coding rna
- lymph node metastasis
- induced apoptosis
- atomic force microscopy
- drinking water
- high speed