Single and concerted effects of benzo[a]pyrene and flavonoids on the AhR and Nrf2-pathway in the human colon carcinoma cell line Caco-2

Niestroy, Jeanette; Barbara, Alfonso; Herbst, Kathrin; Rode, Sandra; Liempt, Manuela van; Roos, Peter H.

doi:10.1016/j.tiv.2011.01.008

Cited by 67 publications

(50 citation statements)

References 77 publications

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“…Our results demonstrate that while fetal brain SOD activity was significantly increased by CYC or DOX exposure, CAT activity was simultaneously decreased in the same tissues. This is consistent with previous reports regarding the mechanisms contributing to oxidative damage of fetal brain tissues (Mihara and Uchiyama 1978;Niestroy et al 2011). Recent studies have implicated oxidative stress in the pathogenesis of a variety of widely prevalent human diseases (Niestroy et al 2011).…”

Section: Discussionsupporting

confidence: 93%

“…This is consistent with previous reports regarding the mechanisms contributing to oxidative damage of fetal brain tissues (Mihara and Uchiyama 1978;Niestroy et al 2011). Recent studies have implicated oxidative stress in the pathogenesis of a variety of widely prevalent human diseases (Niestroy et al 2011). Neurodegenerative disease (Obeid et al 2013), cardiovascular disease (Pryzant et al 1993), cancer (Ray et al 2000), and infertility (Senturker et al 2002) have all been associated with increased oxidative stress.…”

Section: Discussionsupporting

confidence: 91%

“…CAT is an antioxidant enzyme that is itself highly sensitive to oxidative damage, resulting in loss of antioxidant activity. CAT enzymatic activity has been demonstrated to decrease following oxidative damage (Mihara and Uchiyama 1978;Niestroy et al 2011). In the present study, fetal brain tissues were obtained from mothers exposed to the chemotherapeutic drugs CYC and DOX just prior to pregnancy.…”

Section: Discussionmentioning

confidence: 91%

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Effect of chemotherapy exposure prior to pregnancy on fetal brain tissue and the potential protective role of quercetin

et al. 2014

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Cyclophosphamide (CYC) and doxorubicin (DOX) are among the most effective and widely used anticancer chemotherapeutic drugs. Potential chemopreventive and chemotherapeutic functions have recently been attributed to flavonoids. We hypothesized that Quercetin (QR) would protect against the toxic effects of chemotherapeutic agents applied prior to pregnancy. Rats were treated with the chemotherapeutic drugs CYC (27 mg/kg) and DOX (1.8 mg/kg) applied in a single intraperitoneal dose once every 3 weeks for 10 weeks. QR was administered at a dose of 10 mg/kg/day by oral gavage. 48 h following the experimental chemotherapy exposure, female rats were transferred to cages containing male rat for mating. Fetal brain tissues were removed from fetuses extracted by cesarean section on the 20th day of gestation for evaluation of antioxidant parameters. A significant increase in superoxide dismutase and malondialdehyde activity was observed in CYC and DOX treatment groups relative to the control group (p \ 0.05). Similarly, carnitine acylcarnitine translocase and Glutathione activity was significantly reduced in the CYC and DOX groups relative to the control group (p \ 0.05). Our results indicate that the use of chemotherapeutic drugs before pregnancy can result in oxidative damage to fetal brain tissue. Therefore, women who have been exposed to chemotherapy and may become pregnant should be treated with antioxidant compounds such as QR to reduce the risk of damage to fetal brain tissues.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 91%

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Effect of chemotherapy exposure prior to pregnancy on fetal brain tissue and the potential protective role of quercetin

et al. 2014

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“…However, we did not detect activation of NRF2 or expression of its HO1 and NQO1 target genes by BaP as was seen by Niestroy et al [26]. These divergent results can be explained most likely by differences in the doses and/ or times of exposure since the concentrations that we used are much lower (0.34 mM vs. 10 mM) as well as the duration of treatment (4 h vs. 48 h).…”

Section: Pm-awcontrasting

confidence: 58%

“…PAH and metallic compounds are notorious effectors of cellular exposure to PM by provoking an oxidative stress and activation of the ROS-sensitive transcription factor NRF2 (or NFE2L2, Nuclear factor E2-related factor 2) [26,27]. Under basal conditions, NRF2 is sequestered in the cytoplasm due to its interaction with two KEAP1 (Kelch-like ECH-associated protein 1) molecules, which facilitate its ubiquitination and proteasomal degradation.…”

Section: Introductionmentioning

confidence: 99%

The iron component of particulate matter is antiapoptotic: A clue to the development of lung cancer after exposure to atmospheric pollutants?

et al. 2015

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Quercetin, Quercetin Glycosides and Taxifolin Differ in their Ability to Induce AhR Activation and CYP1A1 Expression in HepG2 Cells

Vrba

Křen

Vacek

et al. 2012

Phytotherapy Research

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The natural flavonoid quercetin is a low affinity ligand of the aryl hydrocarbon receptor (AhR), a transcription factor regulating the expression of cytochrome P450 (CYP) 1A enzymes. This study examined the ability of quercetin, isoquercitrin (quercetin-3-O-glucoside), rutin (quercetin-3-O-rutinoside) and taxifolin (dihydroquercetin) to activate AhR and to induce CYP1A1 expression in human hepatoma HepG2 cells. Gene reporter assays showed that quercetin significantly activated AhR and triggered CYP1A1 transcription after 24 h exposure. These effects were, however, much lower than those of 2,3,7,8-tetrachlorodibenzo-p-dioxin, a prototypical AhR ligand. Quercetin also induced a significant increase in CYP1A1 mRNA levels together with a moderate increase in the level of CYP1A1 activity. In contrast, isoquercitrin and rutin had negligible effects on AhR activity and CYP1A1 expression. Taxifolin at the highest concentration tested (50 µm) produced a mild non-significant increase in AhR activity and CYP1A1 transcription. Taxifolin also significantly increased CYP1A1 mRNA expression, but this effect was approximately 15 times weaker than that of quercetin and was not accompanied by induction of CYP1A1 activity. It is concluded that quercetin, but not its 3-O-glycosides isoquercitrin and rutin, induces AhR activation and CYP1A1 expression in HepG2 cells and that the CYP1A1-inducing activity of taxifolin has a low toxicological potential.

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Single and concerted effects of benzo[a]pyrene and flavonoids on the AhR and Nrf2-pathway in the human colon carcinoma cell line Caco-2

Cited by 67 publications

References 77 publications

Effect of chemotherapy exposure prior to pregnancy on fetal brain tissue and the potential protective role of quercetin

Effect of chemotherapy exposure prior to pregnancy on fetal brain tissue and the potential protective role of quercetin

The iron component of particulate matter is antiapoptotic: A clue to the development of lung cancer after exposure to atmospheric pollutants?

Quercetin, Quercetin Glycosides and Taxifolin Differ in their Ability to Induce AhR Activation and CYP1A1 Expression in HepG2 Cells

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