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Clozapine (CLZ) is the most prescribed medication for treating refractory schizophrenia but is associated with significant cardiovascular toxicity. This study aimed to investigate the cardiovascular toxicity induced by CLZ using zebrafish as a model animal. For this purpose, zebrafish developed to 80-h post-fertilization were exposed to different CLZ concentration solutions for 24 h followed by cardiac morphological observations in yolk sac edema, pericardial edema, and blood coagulation, in addition to increased SV-BA distance, functionally manifested as bradycardia, and decreased cardiac ejection fraction using the untreated embryos as control. At the same time, RNA sequencing was used to study the possible molecular mechanism of CLZ-induced cardiovascular toxicity. The results indicated that compared to the control group, the experimental groups possessed a total of 5888 differentially expressed genes (DEGs), where gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment of analysis indicated that DEGs were mainly enriched in the pathways related to ion channels. These findings may provide new insights and directions for the subsequent in-depth study of the molecular mechanism of CLZ-induced cardiovascular toxicity.

Titel:	The cardiovascular toxicity of clozapine in embryonic zebrafish and RNA sequencing-based transcriptome analysis.
Autor/in / Beteiligte Person:	Ding, Z ; Jia, H ; Yang, Z ; Yao, N ; Wang, Y
Link:	Full Text Finder (Volltext)
Zeitschrift:	Journal of applied toxicology : JAT, Jg. 44 (2024-02-01), Heft 2, S. 175-183
Veröffentlichung:	<Apr. 1992- >: Chichester : John Wiley And Sons ; <i>Original Publication</i>: [Philadelphia, Pa. : Heyden & Son, c1981-, 2024
Medientyp:	academicJournal
ISSN:	1099-1263 (electronic)
DOI:	10.1002/jat.4530
Schlagwort:	Animals Transcriptome Sequence Analysis, RNA Gene Expression Profiling Edema Zebrafish Clozapine toxicity Clozapine metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [J Appl Toxicol] 2024 Feb; Vol. 44 (2), pp. 175-183. <i>Date of Electronic Publication: </i>2023 Aug 22. MeSH Terms: Zebrafish* ; Clozapine* / toxicity ; Clozapine* / metabolism ; Animals ; Transcriptome ; Sequence Analysis, RNA ; Gene Expression Profiling ; Edema References: Abdel-Wahab, B. A., & Metwally, M. E. (2015). Clozapine-induced cardiotoxicity: Role of oxidative stress, tumour necrosis factor alpha and NF-kappabeta. Cardiovascular Toxicology, 15, 355-365. https://doi.org/10.1007/s12012-014-9304-9. ; Akande, M. G., Orn, S., & Norrgren, L. (2010). Evaluation of the toxic effects of clozapine in zebrafish (Danio rerio) embryos with the fish embryo toxicity test. International Journal on Pharmaceutical and Biomedical Research, 1, 90-94. ; Ali, S., Champagne, D. L., Spaink, H. P., & Richardson, M. K. (2011). 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Journal of Applied Toxicology, 34, 139-148. https://doi.org/10.1002/jat.2843. Grant Information: KJ2021A0207 Natural Science Foundation of Higher Education of Anhui Province; 2021XKJ003 Research Foundation of Anhui Medical University Contributed Indexing: Keywords: cardiotoxicity; clozapine; toxicology; transcriptome; zebrafish Substance Nomenclature: J60AR2IKIC (Clozapine) Entry Date(s): Date Created: 20230822 Date Completed: 20240115 Latest Revision: 20240520 Update Code: 20240520

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The cardiovascular toxicity of clozapine in embryonic zebrafish and RNA sequencing-based transcriptome analysis.