当前位置： SCI文献检索 > Drug Testing and Analysis期刊下所有文献 > Zebrafish (Danio rerio) water tank model for the investigation of drug metabolism: Progress, outlook, and challenges.

Zebrafish (Danio rerio) water tank model for the investigation of drug metabolism: Progress, outlook, and challenges.

Abstract：

:Zebrafish (Danio rerio) water tank (ZWT) approach was investigated as an alternative model for metabolism studies based on six different experiments with four model compounds. Sibutramine was applied for the multivariate optimization of ZWT conditions, also for the comparison of the metabolism among ZWT, humans and mice, beyond for the role of CYP2B6 in ZWT. After the optimization, 18 fish and 168 hours of experiments is the minimum requirement for a relevant panel of biotransformation products. A comparison among the species resulted in the observation of the same hydroxylated metabolites, with differences in metabolites concentration ratio. However, the ZWT allowed tuning of the conditions to obtain a specific metabolic profile, depending on the need. In addition, by utilizing CYP2B6 inhibition, a relevant ZWT pathway for the demethylation of drugs was determined. The stereospecificity of the ZWT metabolism was investigated using selegiline and no racemization or inversion transformations were observed. Moreover, the investigation of metabolism of cannabimimetics was performed using JWH-073 and the metabolites observed are the same described for humans, except for the hydroxylation at the indol group, which was explained by the absence of CYP2C9 orthologs in zebrafish. Finally, hexarelin was used as a model to evaluate studies by ZWT for drugs with low stability. As a result, hexarelin displays a very fast metabolization in ZWT conditions and all the metabolites described for human were observed in ZWT. Therefore, the appropriate conditions, merits, and relevant limitations to conduct ZWT experiments for the investigation of drug metabolism are described.

journal_name

Drug Test Anal

journal_title

Drug testing and analysis

authors

Sardela VF,Anselmo CS,Nunes IKDC,Carneiro GRA,Dos Santos GRC,de Carvalho AR,Labanca BJ,Silva Oliveira D,Ribeiro WD,de Araujo ALD,Padilha MC,de Lima CKF,de Sousa VP,de Aquino Neto FR,Gualberto Pereira HM

doi

10.1002/dta.2523

subject

Has Abstract

pub_date

2018-11-01 00:00:00

pages

1657-1669

issue

11-12

eissn

1942-7603

issn

1942-7611

journal_volume

pub_type

杂志文章

在线工具

Zebrafish (Danio rerio) water tank model for the investigation of drug metabolism: Progress, outlook, and challenges.