Novel ABCB1 and ABCC Transporters Are Involved in the Detoxification of Benzo(α)pyrene in Thick Shell Mussel, Mytilus coruscus

Guo, Baoying; Xu, Zhongtian; Yan, Xiaojun; Buttino, Isabella; Li, Jiji; Zhou, Chao; Qi, Pengzhi

doi:10.3389/fmars.2020.00119

Cited by 19 publications

(5 citation statements)

References 61 publications

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“…Especially, micro-RNAs(miRNAs) extensively affect their protein level through interaction with target mRNA [ 38 ]. Previous research reported B[a]P induces the mRNA expression of ABCCs, while inhibiting the protein level and function of ABCC transporters [ 39 , 40 ]. In our results, quercetin or isorhamnetin in combination with B[a]P increased both mRNA and protein levels of ABCCs compared to only the B[a]P treated group ( Figure 4 and Figure 5 ).…”

Section: Discussionmentioning

confidence: 99%

Quercetin and Isorhamnetin Attenuate Benzo[a]pyrene-Induced Toxicity by Modulating Detoxification Enzymes through the AhR and NRF2 Signaling Pathways

et al. 2021

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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.

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Section: Discussionmentioning

confidence: 99%

Quercetin and Isorhamnetin Attenuate Benzo[a]pyrene-Induced Toxicity by Modulating Detoxification Enzymes through the AhR and NRF2 Signaling Pathways

et al. 2021

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“…Following GSH-conjugation with B[a]P metabolites via phase II detoxifying enzymes, it is excreted by transporter genes, such as ABCC1 and ABCC2 [17]. Previous studies have showed that ABCC transporters are required to detoxify B[a]P [18]. The knockdown of ABCC2 increases the concentration of B[a]P metabolites in a variety of organs [19].…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of Myricetin on Benzo[a]pyrene-Induced 8-Hydroxy-2′-Deoxyguanosine and BPDE-DNA Adduct

Jee

Kim

et al. 2020

Antioxidants

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Benzo[a]pyrene (B[a]P), a group 1 carcinogen, induces mutagenic DNA adducts. Myricetin is present in many natural foods with diverse biological activities, such as anti-oxidative and anti-cancer activities. The aim of this study was to investigate the protective effects of myricetin against B[a]P-induced toxicity. Treatment of B[a]P induced cytotoxicity on HepG2 cells, whereas co-treatment of myricetin with B[a]P reduced the formation of the B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE)-DNA adduct, which recovered cell viability. Furthermore, we found a protective effect of myricetin against B[a]P-induced genotoxicity in rats, via myricetin-induced inhibition of 8-hydroxy-2′-deoxyguanosine (8-OHdG) and BPDE-DNA adduct formation in the liver, kidney, colon, and stomach tissue. This inhibition was more prominent in the liver than in other tissues. Correspondingly, myricetin regulated the phase I and II enzymes that inhibit B[a]P metabolism and B[a]P metabolites conjugated with DNA by reducing and inducing CYP1A1 and glutathione S-transferase (GST) expression, respectively. Taken together, this showed that myricetin attenuated B[a]P-induced genotoxicity via regulation of phase I and II enzymes. Our results suggest that myricetin is anti-genotoxic, and prevents oxidative DNA damage and BPDE-DNA adduct formation via regulation of phase I and II enzymes.

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“…Nevertheless, some studies suggest their involvement in B[a]P excretion. For instance, in various species, ABC transporters have been identified as responsible for eliminating B[a]P metabolites [48,49]. Furthermore, B[a]P has been shown to reduce the expression levels of ABCA12 [50] and decrease the protein expression level of ABCC1 [51], suggesting a potential hindrance in the proper removal of detoxified B[a]P metabolites from cells due to reduced transporter expression.…”

Section: Metabolism and Excretion Of B[a]p And Their Hepatic Conseque...mentioning

confidence: 99%

Hepatoprotective Effects of Flavonoids against Benzo[a]Pyrene-Induced Oxidative Liver Damage along Its Metabolic Pathways

Kim,

Jee,

Sung

2024

Antioxidants

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Benzo[a]pyrene (B[a]P), a highly carcinogenic polycyclic aromatic hydrocarbon primarily formed during incomplete organic matter combustion, undergoes a series of hepatic metabolic reactions once absorbed into the body. B[a]P contributes to liver damage, ranging from molecular DNA damage to the onset and progression of various diseases, including cancer. Specifically, B[a]P induces oxidative stress via reactive oxygen species generation within cells. Consequently, more research has focused on exploring the underlying mechanisms of B[a]P-induced oxidative stress and potential strategies to counter its hepatic toxicity. Flavonoids, natural compounds abundant in plants and renowned for their antioxidant properties, possess the ability to neutralize the adverse effects of free radicals effectively. Although extensive research has investigated the antioxidant effects of flavonoids, limited research has delved into their potential in regulating B[a]P metabolism to alleviate oxidative stress. This review aims to consolidate current knowledge on B[a]P-induced liver oxidative stress and examines the role of flavonoids in mitigating its toxicity.

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Novel ABCB1 and ABCC Transporters Are Involved in the Detoxification of Benzo(α)pyrene in Thick Shell Mussel, Mytilus coruscus

Cited by 19 publications

References 61 publications

Quercetin and Isorhamnetin Attenuate Benzo[a]pyrene-Induced Toxicity by Modulating Detoxification Enzymes through the AhR and NRF2 Signaling Pathways

Quercetin and Isorhamnetin Attenuate Benzo[a]pyrene-Induced Toxicity by Modulating Detoxification Enzymes through the AhR and NRF2 Signaling Pathways

Protective Effects of Myricetin on Benzo[a]pyrene-Induced 8-Hydroxy-2′-Deoxyguanosine and BPDE-DNA Adduct

Hepatoprotective Effects of Flavonoids against Benzo[a]Pyrene-Induced Oxidative Liver Damage along Its Metabolic Pathways

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