دورية أكاديمية
Zebrafish (Danio rerio) water tank model for the investigation of drug metabolism: Progress, outlook, and challenges.
| العنوان: | Zebrafish (Danio rerio) water tank model for the investigation of drug metabolism: Progress, outlook, and challenges. |
|---|---|
| المؤلفون: | Sardela VF; LBCD-LADETEC, Universidade Federal do Rio de Janeiro, Instituto de Química, Rio de Janeiro, RJ, Brazil., Anselmo CS; LBCD-LADETEC, Universidade Federal do Rio de Janeiro, Instituto de Química, Rio de Janeiro, RJ, Brazil., Nunes IKDC; LBCD-LADETEC, Universidade Federal do Rio de Janeiro, Instituto de Química, Rio de Janeiro, RJ, Brazil., Carneiro GRA; LBCD-LADETEC, Universidade Federal do Rio de Janeiro, Instituto de Química, Rio de Janeiro, RJ, Brazil., Dos Santos GRC; LBCD-LADETEC, Universidade Federal do Rio de Janeiro, Instituto de Química, Rio de Janeiro, RJ, Brazil., de Carvalho AR; LBCD-LADETEC, Universidade Federal do Rio de Janeiro, Instituto de Química, Rio de Janeiro, RJ, Brazil., Labanca BJ; LBCD-LADETEC, Universidade Federal do Rio de Janeiro, Instituto de Química, Rio de Janeiro, RJ, Brazil., Silva Oliveira D; LBCD-LADETEC, Universidade Federal do Rio de Janeiro, Instituto de Química, Rio de Janeiro, RJ, Brazil., Ribeiro WD; LBCD-LADETEC, Universidade Federal do Rio de Janeiro, Instituto de Química, Rio de Janeiro, RJ, Brazil., de Araujo ALD; LBCD-LADETEC, Universidade Federal do Rio de Janeiro, Instituto de Química, Rio de Janeiro, RJ, Brazil., Padilha MC; LBCD-LADETEC, Universidade Federal do Rio de Janeiro, Instituto de Química, Rio de Janeiro, RJ, Brazil., de Lima CKF; Faculty of Pharmacy, Laboratory of Experimental Pharmacology (LEFEx), Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., de Sousa VP; Faculty of Pharmacy, Department of Drugs and Pharmaceutics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., de Aquino Neto FR; LBCD-LADETEC, Universidade Federal do Rio de Janeiro, Instituto de Química, Rio de Janeiro, RJ, Brazil., Gualberto Pereira HM; LBCD-LADETEC, Universidade Federal do Rio de Janeiro, Instituto de Química, Rio de Janeiro, RJ, Brazil. |
| المصدر: | Drug testing and analysis [Drug Test Anal] 2018 Nov; Vol. 10 (11-12), pp. 1657-1669. Date of Electronic Publication: 2018 Nov 22. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: John Wiley & Sons Country of Publication: England NLM ID: 101483449 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1942-7611 (Electronic) Linking ISSN: 19427603 NLM ISO Abbreviation: Drug Test Anal Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Chichester, UK : John Wiley & Sons |
| مواضيع طبية MeSH: | Pharmaceutical Preparations/*metabolism , Zebrafish/*metabolism, Adult ; Animals ; Antidepressive Agents/metabolism ; Antidepressive Agents/urine ; Biotransformation ; Cyclobutanes/metabolism ; Cyclobutanes/urine ; Cytochrome P-450 CYP2B6/metabolism ; Cytochrome P-450 CYP2B6 Inhibitors/pharmacology ; Female ; Humans ; Hydroxylation ; Indoles/metabolism ; Indoles/urine ; Male ; Mice ; Models, Animal ; Naphthalenes/metabolism ; Naphthalenes/urine ; Oligopeptides/metabolism ; Oligopeptides/urine ; Pharmaceutical Preparations/urine ; Selegiline/metabolism ; Selegiline/urine ; Zebrafish/urine ; Zebrafish Proteins/metabolism |
| مستخلص: | 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. (© 2018 John Wiley & Sons, Ltd.) |
| معلومات مُعتمدة: | Ministério do Esporte; FAPERJ; CNPq |
| فهرسة مساهمة: | Keywords: CYP2B6; Zebrafish water tank; doping control; drug metabolism; mass spectrometry |
| المشرفين على المادة: | 0 (Antidepressive Agents) 0 (Cyclobutanes) 0 (Cytochrome P-450 CYP2B6 Inhibitors) 0 (Indoles) 0 (Naphthalenes) 0 (Oligopeptides) 0 (Pharmaceutical Preparations) 0 (Zebrafish Proteins) 09QF37C617 (hexarelin) 2K1V7GP655 (Selegiline) BBX3BP2772 (JWH-073) EC 1.14.14.1 (Cytochrome P-450 CYP2B6) WV5EC51866 (sibutramine) |
| تواريخ الأحداث: | Date Created: 20181021 Date Completed: 20190401 Latest Revision: 20190401 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1002/dta.2523 |
| PMID: | 30341930 |
| قاعدة البيانات: | MEDLINE |
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