Metabolism of clofibric acid in zebrafish embryos ( Danio rerio ) as determined by liquid chromatography–high resolution–mass spectrometry

Brox, Stephan; Seiwert, Bettina; Haase, Nora; Küster, Eberhard; Reemtsma, Thorsten

doi:10.1016/j.cbpc.2016.02.007

Cited by 35 publications

(56 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although some mammalian homologs have been identified, functional conservation has not yet been established for most CYPs [53] across common fish models. For example, investigations of clofibric acid biotransformation [55], and a suite of other polar compounds [40], by developing zebrafish identified the presence of transformation products. For example, investigations of clofibric acid biotransformation [55], and a suite of other polar compounds [40], by developing zebrafish identified the presence of transformation products.…”

Section: Resultsmentioning

confidence: 99%

“…However, studies have explored xenobiotic metabolism in developing zebrafish. For example, investigations of clofibric acid biotransformation [55], and a suite of other polar compounds [40], by developing zebrafish identified the presence of transformation products. Relationships among biotransformation capacities of developing and mature fish models, however, require additional study.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Differential uptake of and sensitivity to diphenhydramine in embryonic and larval zebrafish

Kristofco

Haddad

Chambliss³

et al. 2018

Enviro Toxic and Chemistry

View full text Add to dashboard Cite

The zebrafish fish embryo toxicity (FET) test is increasingly employed for alternative toxicity studies, yet our previous research identified increased sensitivity of zebrafish slightly older than embryos employed in FET methods (0-4 d postfertilization [dpf]). We identified rapid steady-state accumulation of diphenhydramine across zebrafish embryo and larval stages. However, significantly (p < 0.05) lower accumulation was observed at 48 h compared to 96 h in chorionated and dechorionated embryos (0-4 dpf), but not in zebrafish at 7 to 11 and 14 to 18 dpf. Increased uptake and toxicity of diphenhydramine was further observed in zebrafish at 7 to 11 and 14 to 18 dpf compared with 0-4 dpf embryos with chorion or dechorionated, which indicates that differential zebrafish sensitivity with age is associated with accumulation resulting from gill and other toxicokinetic and toxicodynamic changes during development. Environ Toxicol Chem 2018;37:1175-1181. © 2017 SETAC.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Differential uptake of and sensitivity to diphenhydramine in embryonic and larval zebrafish

Kristofco

Haddad

Chambliss³

et al. 2018

Enviro Toxic and Chemistry

View full text Add to dashboard Cite

show abstract

“…Using an in vitro approach based on the use of sub-cellular microsomal fractions and of specific probe substrates, Verbueken et al [25] concluded that the capacity of intrinsic biotransformation in zebrafish embryos appears to be lacking during a major part of organogenesis, at least concerning key phase I activities. Notwithstanding, recent in vivo studies demonstrated that biotransformation of some compounds can start very early, indicating that some phase I and phase II enzymes are already functional at early life-stages [26,27]. We previously demonstrated that the metabolic capacities expressed in zebrafish hepatic cellular models are close to that of metabolically competent hepatic human cell lines (HepaRG), at least for BPS and BP2 [8].…”

Section: Introductionmentioning

confidence: 99%

Comparison of the In Vivo Biotransformation of Two Emerging Estrogenic Contaminants, BP2 and BPS, in Zebrafish Embryos and Adults

Fol

Brion

Hillenweck

et al. 2017

IJMS

View full text Add to dashboard Cite

Zebrafish embryo assays are increasingly used in the toxicological assessment of endocrine disruptors. Among other advantages, these models are 3R-compliant and are fit for screening purposes. Biotransformation processes are well-recognized as a critical factor influencing toxic response, but major gaps of knowledge exist regarding the characterization of functional metabolic capacities expressed in zebrafish. Comparative metabolic studies between embryos and adults are even scarcer. Using 3H-labeled chemicals, we examined the fate of two estrogenic emerging contaminants, benzophenone-2 (BP2) and bisphenol S (BPS), in 4-day embryos and adult zebrafish. BPS and BP2 were exclusively metabolized through phase II pathways, with no major qualitative difference between larvae and adults except the occurrence of a BP2-di-glucuronide in adults. Quantitatively, the biotransformation of both molecules was more extensive in adults. For BPS, glucuronidation was the predominant pathway in adults and larvae. For BP2, glucuronidation was the major pathway in larvae, but sulfation predominated in adults, with ca. 40% conversion of parent BP2 and an extensive release of several conjugates into water. Further larvae/adults quantitative differences were demonstrated for both molecules, with higher residue concentrations measured in larvae. The study contributes novel data regarding the metabolism of BPS and BP2 in a fish model and shows that phase II conjugation pathways are already functional in 4-dpf-old zebrafish. Comparative analysis of BP2 and BPS metabolic profiles in zebrafish larvae and adults further supports the use of zebrafish embryo as a relevant model in which toxicity and estrogenic activity can be assessed, while taking into account the absorption and fate of tested substances.

show abstract

“…So, zebrafish is emerging as a predictive vertebrate animal model for in vivo assessment of drug efficacy, toxicity, and safety . Besides, some studies have evaluated the ability of zebrafish larvae at different stages of ripening to generate xenobiotic metabolites . However, studies have shown a difference either in the function or expression of the drug‐metabolizing enzymes between zebrafish larvae and adult zebrafish, suggesting that adults are more effective in generating xenobiotic metabolites .…”

Section: Introductionmentioning

confidence: 99%

Is zebrafish (Danio rerio) a tool for human‐like metabolism study?

Anselmo

Sardela

Matias

et al. 2017

Drug Testing and Analysis

View full text Add to dashboard Cite

One of the greatest challenges in anti-doping science is the large number of substances available and the difficulty in finding the best analytical targets to detect their misuse. Therefore, metabolism studies involving prohibited substances are fundamental. However, metabolism studies in humans could face an important ethical bottleneck, especially for non-approved substances. An emerging model for metabolism assessment is the zebrafish, due to its genetic similarities with humans. In the present study, the ability of adult zebrafish to produce metabolites of sibutramine and stanozolol, substances with a well-known metabolism that are widely used as doping agents in sports, was evaluated. They represent 2 of the most abused classes of doping agents, namely, stimulants and anabolic steroids. These are classes that have been receiving attention because of the upsurge of synthetic analogues, for which the side effects in humans have not been assessed. The samples collected from the zebrafish tank water were hydrolysed, extracted by solid-phase extraction, and analysed by liquid chromatography with high resolution mass spectrometry (LC-HRMS). Adult zebrafish could produce several sibutramine and stanozolol metabolites, including demethylated, hydroxylated, dehydroxylated, and reduced derivatives, all of which have already been detected in human urine. This study demonstrates that adult zebrafish can absorb, oxidise, and excrete several metabolites in a manner similar to humans. Therefore, adult zebrafish seem to be a very promising tool to study human-like metabolism when aiming to find analytical targets for doping control.

show abstract

Metabolism of clofibric acid in zebrafish embryos ( Danio rerio ) as determined by liquid chromatography–high resolution–mass spectrometry

Cited by 35 publications

References 51 publications

Differential uptake of and sensitivity to diphenhydramine in embryonic and larval zebrafish

Differential uptake of and sensitivity to diphenhydramine in embryonic and larval zebrafish

Comparison of the In Vivo Biotransformation of Two Emerging Estrogenic Contaminants, BP2 and BPS, in Zebrafish Embryos and Adults

Is zebrafish (Danio rerio) a tool for human‐like metabolism study?

Contact Info

Product

Resources

About