Inducibility of cytochrome P450-mediated 7-methoxycoumarin-O-demethylase activity in zebrafish (Danio rerio) embryos

Loerracher, Ann-Kathrin; Braunbeck, Thomas

doi:10.1016/j.aquatox.2020.105540

Cited by 14 publications

(5 citation statements)

References 72 publications

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“…7-MC is relatively specific for CYP2A6 rather than CYP2E [ 23 ]. It was reported that β-naphthoflavone, an aryl hydrocarbon receptor (AhR) agonist, induced MCOD activity in zebrafish larvae at 96 hpf [ 24 ]. It is well known that AhR agonists induce CYP3A65 in addition to CYP1A and CYP1B in zebrafish [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

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Transgenic Zebrafish Expressing Rat Cytochrome P450 2E1 (CYP2E1): Augmentation of Acetaminophen-Induced Toxicity in the Liver and Retina

Sato

Dong

Nakamura

et al. 2023

IJMS

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Metabolic activation is the primary cause of chemical toxicity including hepatotoxicity. Cytochrome P450 2E (CYP2E) is involved in this process for many hepatotoxicants, including acetaminophen (APAP), one of the most common analgesics and antipyretics. Although the zebrafish is now used as a model for toxicology and toxicity tests, the CYP2E homologue in zebrafish has not been identified yet. In this study, we prepared transgenic zebrafish embryos/larvae expressing rat CYP2E1 and enhanced green fluorescent protein (EGFP) using a β-actin promoter. Rat CYP2E1 activity was confirmed by the fluorescence of 7-hydroxycoumarin (7-HC), a metabolite of 7-methoxycoumarin that was specific for CYP2 in transgenic larvae with EGFP fluorescence (EGFP [+]) but not in transgenic larvae without EGFP fluorescence (EGFP [−]). APAP (2.5 mM) caused reduction in the size of the retina in EGFP [+] larvae but not in EGFP [−] larvae, while APAP similarly reduced pigmentation in both larvae. APAP at even 1 mM reduced the liver size in EGFP [+] larvae but not in EGFP [−] larvae. APAP-induced reduction of liver size was inhibited by N-acetylcysteine. These results suggest that rat CYP2E1 is involved in some APAP-induced toxicological endpoints in the retina and liver but not in melanogenesis of the developing zebrafish.

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Section: Discussionmentioning

confidence: 99%

“…7-Methoxycoumarin (7-MC) was used as a fluorogenic substrate that is specific for CYP2 [ 9 , 23 , 24 ]. Zebrafish embryos/larvae were exposed to 100 µM 7-MC (with 0.01% DMSO) in ZR solution from 48 hpf to 54 hpf in a 3.5 cm plastic petri dish (AGC Technoglass, Yoshida, Japan).…”

Section: Methodsmentioning

confidence: 99%

Transgenic Zebrafish Expressing Rat Cytochrome P450 2E1 (CYP2E1): Augmentation of Acetaminophen-Induced Toxicity in the Liver and Retina

Sato

Dong

Nakamura

et al. 2023

IJMS

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“…In the second stage, hepatoblasts aggregate between 24 and 28 h, which leads to the thickening in the intestinal primordium (Hill 2012 ), and the initiation of differentiation. Molecular markers of mature hepatocytes and biliary epithelial cells are detectable at 32 h ( ceruloplasmin ) and 48 h ( transferrin and L-FABP ) (Chu and Sadler 2009 ; Wilkins and Pack 2013 ), and CYP-mediated metabolism (be it hepatocellular or extrahepatic) is already active at 36 h (Lörracher and Braunbeck 2020 ). At 48 h, the liver primordium is clearly discernable as a prominent bud extending from the left of the midline over the yolk (Chu and Sadler 2009 ), and at approximately 50 h liver tissue is easily recognizable (Hill 2012 ).…”

Section: Discussionmentioning

confidence: 99%

Potential of the zebrafish (Danio rerio) embryo test to discriminate between chemicals of similar molecular structure—a study with valproic acid and 14 of its analogues

et al. 2022

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Valproic acid is a frequently used antiepileptic drug and known pediatric hepatotoxic agent. In search of pharmaceuticals with increased effectiveness and reduced toxicity, analogue chemicals came into focus. So far, toxicity and teratogenicity data of drugs and metabolites have usually been collected from mammalian model systems such as mice and rats. However, in an attempt to reduce mammalian testing while maintaining the reliability of toxicity testing of new industrial chemicals and drugs, alternative test methods are being developed. To this end, the potential of the zebrafish (Danio rerio) embryo to discriminate between valproic acid and 14 analogues was investigated by exposing zebrafish embryos for 120 h post fertilization in the extended version of the fish embryo acute toxicity test (FET; OECD TG 236), and analyzing liver histology to evaluate the correlation of liver effects and the molecular structure of each compound. Although histological evaluation of zebrafish liver did not identify steatosis as the prominent adverse effect typical in human and mice, the structure–activity relationship (SAR) derived was comparable not only to human HepG2 cells, but also to available in vivo mouse and rat data. Thus, there is evidence that zebrafish embryos might serve as a tool to bridge the gap between subcellular, cell-based systems and vertebrate models.

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“…Concerning potential (apical) endpoints of neurotoxicity, the development of locomotor behavior can be studied (Brockerhoff et al 1995 ; Chandrasekhar et al 1997 ; Blader 2000 ; Claudio et al 2000 ; Arslanova et al 2010 ; Brocardo et al 2012 ; Baiamonte et al 2016 ; Zindler et al 2019b , 2020b ). In addition to a standardized set of morphological criteria for acute toxicity in the fish embryo acute toxicity (FET) test OECD TG 236 (OECD 2013 ), a whole suite of additional endpoints of ecotoxicological relevance can be made accessible by minor modifications of the protocol, which may cover teratogenicity (Brotzmann et al 2019 ; von Hellfeld et al 2020 ; Escher et al 2022 ), endocrine disruption (e.g., Islinger et al 2002 ; Wang et al 2019c ; Yao et al 2020 ; Zhou et al 2020 ), induction of biotransformation (e.g., Goldstone et al 2010 ; Loerracher et al 2020b , a ; Loerracher and Braunbeck 2021 ), or neurotoxicity (e.g., Bolon et al 2011 ; Kais et al 2015 , 2017 ; Stengel et al 2018 ; Zindler et al 2020a ; Brotzmann et al 2021 ; Wlodkowic et al 2022 ; Kämmer et al 2022 ).…”

Section: Introductionmentioning

confidence: 99%

The sensitivity of the zebrafish embryo coiling assay for the detection of neurotoxicity by compounds with diverse modes of action

Hellfeld

Gade

Baumann

et al. 2023

Environ Sci Pollut Res

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In the aim to determine neurotoxicity, new methods are being validated, including tests and test batteries comprising in vitro and in vivo approaches. Alternative test models such as the zebrafish (Danio rerio) embryo have received increasing attention, with minor modifications of the fish embryo toxicity test (FET; OECD TG 236) as a tool to assess behavioral endpoints related to neurotoxicity during early developmental stages. The spontaneous tail movement assay, also known as coiling assay, assesses the development of random movement into complex behavioral patterns and has proven sensitive to acetylcholine esterase inhibitors at sublethal concentrations. The present study explored the sensitivity of the assay to neurotoxicants with other modes of action (MoAs). Here, five compounds with diverse MoAs were tested at sublethal concentrations: acrylamide, carbaryl, hexachlorophene, ibuprofen, and rotenone. While carbaryl, hexachlorophene, and rotenone consistently induced severe behavioral alterations by ~ 30 h post fertilization (hpf), acrylamide and ibuprofen expressed time- and/or concentration-dependent effects. At 37–38 hpf, additional observations revealed behavioral changes during dark phases with a strict concentration-dependency. The study documented the applicability of the coiling assay to MoA-dependent behavioral alterations at sublethal concentrations, underlining its potential as a component of a neurotoxicity test battery.

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Inducibility of cytochrome P450-mediated 7-methoxycoumarin-O-demethylase activity in zebrafish (Danio rerio) embryos

Cited by 14 publications

References 72 publications

Transgenic Zebrafish Expressing Rat Cytochrome P450 2E1 (CYP2E1): Augmentation of Acetaminophen-Induced Toxicity in the Liver and Retina

Transgenic Zebrafish Expressing Rat Cytochrome P450 2E1 (CYP2E1): Augmentation of Acetaminophen-Induced Toxicity in the Liver and Retina

Potential of the zebrafish (Danio rerio) embryo test to discriminate between chemicals of similar molecular structure—a study with valproic acid and 14 of its analogues

The sensitivity of the zebrafish embryo coiling assay for the detection of neurotoxicity by compounds with diverse modes of action

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