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


引用次數
Scopus ( 21/11/2020)
替代計量分析
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其它資訊
摘要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.
著者Ng 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
期刊名稱Biomedicine and Pharmacotherapy
出版年份2020
月份12
卷號132
出版社Elsevier
文章號碼110749
國際標準期刊號0753-3322
電子國際標準期刊號1950-6007
語言美式英語
關鍵詞clofazimine, zebrafish, tuberculosis, cardiac dysfunction

上次更新時間 2020-21-11 於 23:47