Role of oxidative stress in clofazimine-induced cardiac dysfunction in a zebrafish model
Publication in refereed journal


Times Cited
Web of Science0WOS source URL (as at 17/01/2021) Click here for the latest count
Altmetrics Information
.

Other information
AbstractBackground
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.
All Author(s) ListNg PCI, Chan JYW, Leung RKK, Li J, Ren Z, Chan AWH, Xu Y, Lee SS, Wang R, Ji X, Zheng J, Chan DPC, Yew WW, Lee SMY
Journal nameBiomedicine and Pharmacotherapy
Year2020
Month12
Volume Number132
PublisherElsevier
Article number110749
ISSN0753-3322
eISSN1950-6007
LanguagesEnglish-United States
Keywordsclofazimine, zebrafish, tuberculosis, cardiac dysfunction

Last updated on 2021-17-01 at 23:54