Fluconazole induces cardiovascular toxicity in zebrafish by promoting oxidative stress, apoptosis, and disruption of key developmental genes

作者：Hanzhi Wu, Gang Zhao, Wubing Feng, Chenjian Yang, Jiang Yu · 发表于：Chemico-Biological Interactions · 年份：2025 · DOI：10.1016/j.cbi.2025.111391 · 被引用次数：11 · 研究领域：Mitochondrial Function and Pathology、Nitric Oxide and Endothelin Effects、Cardiac Ischemia and Reperfusion

This study systematically evaluated the toxic effects of fluconazole on the cardiovascular development of zebrafish. Zebrafish embryos were treated with different concentrations of fluconazole (200, 400, and 800 μg/ml) to observe its impact on heart development, reactive oxygen species (ROS) generation, apoptosis, and hemoglobin production. The results showed that as the concentration of fluconazole increased, significant changes in zebrafish heart structure were observed, along with a notable reduction in heart rate. Pericardial edema and cardiac morphological abnormalities were particularly prominent in the high-dose group. In addition, fluconazole treatment significantly increased ROS levels and induced apoptosis in cardiac cells. Enzyme-linked immunosorbent assay (ELISA) results showed that fluconazole treatment significantly increased the malondialdehyde (MDA) content and reduced superoxide dismutase (SOD) and catalase (CAT) activity, suggesting that oxidative stress and cell death may play a key role in its cardiotoxicity. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis revealed that fluconazole treatment significantly affected the expression of several key genes related to heart development and function, particularly cardiac myosin light chain 2 ( cmlc2 ), ventricular myosin heavy chain ( vmhc ), and myosin heavy chain 6 ( myh6 ), whose expression changes were closely associated with alterations in heart morphology and function. Transcri...