Environmental pollutants parathion, paraquat and bisphenol A show distinct effects towards nuclear receptors-mediated induction of xenobiotics-metabolizing cytochromes P450 in human hepatocytes

Vrzal, Radim; Ženata, Ondřej; Doricakova, Aneta; Dvořák, Zdeněk

doi:10.1016/j.toxlet.2015.07.008

Cited by 27 publications

(20 citation statements)

References 70 publications

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“…13 The cytochrome P450 system (CYP450s) belongs to a multigene family of heme proteins that, in addition to their role in the metabolism of xenobiotics (such as ATR) in hepatocytes, are also expressed in neurocytes. 14,15 Exogenous substances interact with the CYPs, generating oxidation products that cause biological macromolecules damage and then tissue injury. 16−19 It is generally known that the metabolism of xenobiotic via alterations in the CYP450s provides useful biomarkers to the field of ecotoxicology assays.…”

Section: ■ Introductionmentioning

confidence: 99%

Atrazine Triggers Mitochondrial Dysfunction and Oxidative Stress in Quail (Coturnix C. coturnix) Cerebrum via Activating Xenobiotic-Sensing Nuclear Receptors and Modulating Cytochrome P450 Systems

Lin

Zhao

Qin

et al. 2018

J. Agric. Food Chem.

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The residues from the widely used broad-spectrum environmental herbicide, atrazine (ATR), result in the exposure of nontarget organisms and persist as a global major public health hazard. ATR is neurotoxic and may cause adverse health effects in mammals, birds, and fishes. Nevertheless, the molecular mechanism of ATR induced neurotoxicity remains unclear. To assess the molecular mechanisms of ATR-induced cerebral toxicity through potential oxidative damage, quail were treated with ATR by oral gavage administration at doses of 0, 50, 250, and 500 mg/kg body weight daily for 45 days. Markedly, increases in the amount of swelling of neuronal cells, the percentage of mean damaged mitochondria, mitochondrial malformation, and mitochondrial vacuolar degeneration as well as decreases in the mitochondrial cristae and mitochondrial volume density were observed by light and electron microscopy in the cerebrum of quail. ATR induced toxicities in the expression of mitochondrial function-related genes and promoted oxidative damage, as indicated by effects on oxidative stress indices. These results indicated that ATR exposure can cause neurological disorders and cerebral injury. ATR may initiate apoptosis by activating Bcl-2, Bax, and Caspase3 protein expression but failed to induce autophagy (LC3B has not cleaved to LC3BI/II). Furthermore, ATR induced CYP-related enzymes metabolism disorders by activating the nuclear xenobiotic receptors response (NXRs including AHR, CAR, and PXR) and increased expression of several CYP isoforms (including CYP1B1 and CYP2C18) and thereby producing mitochondrial dysfunction. In this study, we observed ATR exposure resulted in oxidative stress and mitochondrial dysfunction by activating the NXR response and interfering the CYP450s homeostasis in quail cerebrum that supported the molecular mechanism of ATR induced cerebrum toxicity. In conclusion, these results provided new evidence on molecular mechanism of ATR induced neurotoxicity.

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Section: ■ Introductionmentioning

confidence: 99%

Atrazine Triggers Mitochondrial Dysfunction and Oxidative Stress in Quail (Coturnix C. coturnix) Cerebrum via Activating Xenobiotic-Sensing Nuclear Receptors and Modulating Cytochrome P450 Systems

Lin

Zhao

Qin

et al. 2018

J. Agric. Food Chem.

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“…In addition, Sui et al [31] suggested a possible role of bisphenol A in cardiovascular disease in PXR-humanized apolipoprotein-deficient mice. Bisphenol A has also been reported to be the activator of the aryl hydrocarbon receptor (AhR) and SXR in hepatoma cells (HepG2) as well as in human hepatocytes [39]. Bisphenol A also possesses an anti-glucocorticoid action in human hepatocytes [39].…”

Section: Discussionmentioning

confidence: 99%

“…Bisphenol A has also been reported to be the activator of the aryl hydrocarbon receptor (AhR) and SXR in hepatoma cells (HepG2) as well as in human hepatocytes [39]. Bisphenol A also possesses an anti-glucocorticoid action in human hepatocytes [39]. In bone tissues, the AhR located in osteoclasts has an important role in bone metabolism by inducing bone resorption [44].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, it is thought to exert endocrine disrupting effects on reproduction, neuronal development, immune response, and cardiovascular functions through the stimulation of the ER pathway [27]. However, bisphenol A also binds to several other nuclear receptors, including aryl hydrocarbon receptor [11], estrogen-related receptor γ [16], and SXR [14,35,39]. Results from animal experiments demonstrated that intrauterine exposure to bisphenol A during pregnancy does not necessarily result in skeletal malformations in the fetus [21].…”

Section: Introductionmentioning

confidence: 99%

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Steroid and xenobiotic receptor-mediated effects of bisphenol A on human osteoblasts

et al. 2016

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“…This group examined several different compounds, including BPA, for their involvement with nuclear receptors in human hepatocytes. 44 They found that BPA, along with parathion, activates arylhydrocarbon receptor (AhR), and therefore may play a role in many biological processes. There was only a single review article in 2016, and it concerned the replacement of BPA with BPS.…”

Section: Bisphenol Research In Slovenia Poland and The Czech Republicmentioning

confidence: 99%

The state of bisphenol research in the lesser developed countries of the EU: a mini-review

Thoene

Rytel

Nowicka

et al. 2018

Toxicology Research

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Bisphenol compounds are a class of chemical epoxy resins that are found throughout the world in food packaging, thermal paper products, dental materials, and more. These compounds were deemed to be safe until recently, when some studies noticed adverse effects at very low doses, due to the fact that bisphenol acts as an endocrine disruptor. Over the last ten years, studies have been performed to detect bisphenols (especially BPA) in serum and blood samples throughout the world. Essentially, the majority of the earth's population seems to have significantly measurable levels of bisphenol in their blood plasma or urine. However, the majority of the population is unaware that a potential danger may exist. The purpose of this mini-review is to report upon the state of bisphenol research in the lesser developed member-states of the European Union and to increase awareness of the exposure level and possible adverse health effects of this endocrine disruptor. The results show that only three of the most newly admitted members of the European Union have published research concerning the health effects and/or environmental exposure of EU citizens to bisphenol compounds. Those countries were Slovenia, Poland and the Czech Republic. The rest of the surveyed member-states had little or no published research in relation to bisphenol compounds. Furthermore, even the three nations referred to above still lagged far behind the more advanced EU member-states. The lack of research could translate into a lack of awareness amongst the citizenry of nearly half of the EU, and may be unnecessarily putting those EU citizens at an increased risk of exposure.

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Environmental pollutants parathion, paraquat and bisphenol A show distinct effects towards nuclear receptors-mediated induction of xenobiotics-metabolizing cytochromes P450 in human hepatocytes

Cited by 27 publications

References 70 publications

Atrazine Triggers Mitochondrial Dysfunction and Oxidative Stress in Quail (Coturnix C. coturnix) Cerebrum via Activating Xenobiotic-Sensing Nuclear Receptors and Modulating Cytochrome P450 Systems

Atrazine Triggers Mitochondrial Dysfunction and Oxidative Stress in Quail (Coturnix C. coturnix) Cerebrum via Activating Xenobiotic-Sensing Nuclear Receptors and Modulating Cytochrome P450 Systems

Steroid and xenobiotic receptor-mediated effects of bisphenol A on human osteoblasts

The state of bisphenol research in the lesser developed countries of the EU: a mini-review

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