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Role of oxidative stress in clofazimine-induced cardiac dysfunction in a zebrafish model
Ng,Phoebe C.I.1; Chan,Judy Y.W.1; Leung,Ross K.K.2,3; Li,J.1; Ren,Z.1; Chan,Anthony W.H.4; Xu,Y.3; Lee,S. S.3; Wang,R.1; Ji,Xia5; Zheng,Jun5; Chan,Denise P.C.3; Yew,W. W.3; Lee,Simon M.Y.1
2020-12-01
Source PublicationBiomedicine and Pharmacotherapy
ISSN0753-3322
Volume132
Abstract

Background: Clofazimine (CFZ), a riminophenazine, is now commonly used in the treatment of multidrug-resistant tuberculosis. However, its use may be potentially associated with cardiac dysfunction in some individuals. In this study, the zebrafish heart, by merit of its developmental and genetic characteristics being in homology with that of human, was chosen as an animal model for evaluation of such dysfunction. Methods: Morphological and physiological parameters were used to assess cardiac dysfunction. Transcriptome analysis was performed, followed by validation with real-time quantitative PCR, for delineation of the relevant genomics. Results: Exposure of 2 dpf zebrafish to 4 mg/L CFZ for 2 days, adversely affected cardiac functions including significant decreases in HR, SV, CO, and FS, with observable pathophysiological developments of pericardial effusion and blood accumulation in the heart, in comparison with the control group. In addition, genes which respond to xenobiotic stimulus, related to oxygen transport, glutathione metabolism and extracellular matrix -receptor interactions, were significantly enriched among the differentially up-regulated genes. Antioxidant response element motif was enriched in the 5000 base pair upstream regions of the differentially expressed genes. Co-administration of N-acetylcysteine was shown to protect zebrafish against the development of CFZ-induced cardiac dysfunction. Conclusions: This study suggests an important role of oxidative stress as a major pathogenetic mechanism of riminophenazine-induced cardiac dysfunction.

KeywordCardiac Dysfunction Clofazimine Oxidative Stress
DOI10.1016/j.biopha.2020.110749
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaResearch & Experimental Medicine ; Pharmacology & Pharmacy
WOS SubjectMedicine, Research & Experimental ; Pharmacology & Pharmacy
WOS IDWOS:000593699800004
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Document TypeJournal article
CollectionFaculty of Health Sciences
Institute of Chinese Medical Sciences
Corresponding AuthorChan,Denise P.C.; Yew,W. W.; Lee,Simon M.Y.
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences,University of Macau,Macao,Macao
2.School of Public Health,University of Hong Kong,Hong Kong,Hong Kong
3.Stanley Ho Centre for Emerging Infectious Diseases,Chinese University of Hong Kong,Hong Kong,Hong Kong
4.Department of Anatomical & Cellular Pathology,Chinese University of Hong Kong,Hong Kong,Hong Kong
5.Faculty of Health Sciences,University of Macau,Macao,Macao
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Ng,Phoebe C.I.,Chan,Judy Y.W.,Leung,Ross K.K.,et al. Role of oxidative stress in clofazimine-induced cardiac dysfunction in a zebrafish model[J]. Biomedicine and Pharmacotherapy,2020,132.
APA Ng,Phoebe C.I.,Chan,Judy Y.W.,Leung,Ross K.K.,Li,J.,Ren,Z.,Chan,Anthony W.H.,Xu,Y.,Lee,S. S.,Wang,R.,Ji,Xia,Zheng,Jun,Chan,Denise P.C.,Yew,W. W.,&Lee,Simon M.Y..(2020).Role of oxidative stress in clofazimine-induced cardiac dysfunction in a zebrafish model.Biomedicine and Pharmacotherapy,132.
MLA Ng,Phoebe C.I.,et al."Role of oxidative stress in clofazimine-induced cardiac dysfunction in a zebrafish model".Biomedicine and Pharmacotherapy 132(2020).
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