Apatinib induces zebrafish hepatotoxicity by inhibiting Wnt signaling and accumulation of oxidative stress
Ling Huang
Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, College of Life Sciences, Clinical Research Center of Affiliated Hospital of Jinggangshan University, Jinggangshan University, Ji'an, China
Search for more papers by this authorZhipeng Wang
Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, College of Life Sciences, Clinical Research Center of Affiliated Hospital of Jinggangshan University, Jinggangshan University, Ji'an, China
Search for more papers by this authorJieping Liu
Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, College of Life Sciences, Clinical Research Center of Affiliated Hospital of Jinggangshan University, Jinggangshan University, Ji'an, China
Search for more papers by this authorMengqi Wan
Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, College of Life Sciences, Clinical Research Center of Affiliated Hospital of Jinggangshan University, Jinggangshan University, Ji'an, China
Search for more papers by this authorJiejun Liu
Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, College of Life Sciences, Clinical Research Center of Affiliated Hospital of Jinggangshan University, Jinggangshan University, Ji'an, China
Search for more papers by this authorFasheng Liu
Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, College of Life Sciences, Clinical Research Center of Affiliated Hospital of Jinggangshan University, Jinggangshan University, Ji'an, China
Search for more papers by this authorXiaofei Tu
Department of General Surgery, The Affiliated Children's Hospital of Nanchang University, Nanchang, China
Search for more papers by this authorJuhua Xiao
Department of Ultrasound, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, China
Search for more papers by this authorXinjun Liao
Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, College of Life Sciences, Clinical Research Center of Affiliated Hospital of Jinggangshan University, Jinggangshan University, Ji'an, China
Search for more papers by this authorHuiqiang Lu
Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, College of Life Sciences, Clinical Research Center of Affiliated Hospital of Jinggangshan University, Jinggangshan University, Ji'an, China
Search for more papers by this authorCorresponding Author
Shouhua Zhang
Department of General Surgery, The Affiliated Children's Hospital of Nanchang University, Nanchang, China
Correspondence
Zigang Cao, School of Life Sciences, Jinggangshan University, Ji'an 343009, China.
Email: [email protected]
Shouhua Zhang, Department of General Surgery, The Affiliated Children's Hospital of Nanchang University, Nanchang 330006, China.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Zigang Cao
Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, College of Life Sciences, Clinical Research Center of Affiliated Hospital of Jinggangshan University, Jinggangshan University, Ji'an, China
Correspondence
Zigang Cao, School of Life Sciences, Jinggangshan University, Ji'an 343009, China.
Email: [email protected]
Shouhua Zhang, Department of General Surgery, The Affiliated Children's Hospital of Nanchang University, Nanchang 330006, China.
Email: [email protected]
Search for more papers by this authorLing Huang
Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, College of Life Sciences, Clinical Research Center of Affiliated Hospital of Jinggangshan University, Jinggangshan University, Ji'an, China
Search for more papers by this authorZhipeng Wang
Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, College of Life Sciences, Clinical Research Center of Affiliated Hospital of Jinggangshan University, Jinggangshan University, Ji'an, China
Search for more papers by this authorJieping Liu
Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, College of Life Sciences, Clinical Research Center of Affiliated Hospital of Jinggangshan University, Jinggangshan University, Ji'an, China
Search for more papers by this authorMengqi Wan
Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, College of Life Sciences, Clinical Research Center of Affiliated Hospital of Jinggangshan University, Jinggangshan University, Ji'an, China
Search for more papers by this authorJiejun Liu
Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, College of Life Sciences, Clinical Research Center of Affiliated Hospital of Jinggangshan University, Jinggangshan University, Ji'an, China
Search for more papers by this authorFasheng Liu
Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, College of Life Sciences, Clinical Research Center of Affiliated Hospital of Jinggangshan University, Jinggangshan University, Ji'an, China
Search for more papers by this authorXiaofei Tu
Department of General Surgery, The Affiliated Children's Hospital of Nanchang University, Nanchang, China
Search for more papers by this authorJuhua Xiao
Department of Ultrasound, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, China
Search for more papers by this authorXinjun Liao
Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, College of Life Sciences, Clinical Research Center of Affiliated Hospital of Jinggangshan University, Jinggangshan University, Ji'an, China
Search for more papers by this authorHuiqiang Lu
Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, College of Life Sciences, Clinical Research Center of Affiliated Hospital of Jinggangshan University, Jinggangshan University, Ji'an, China
Search for more papers by this authorCorresponding Author
Shouhua Zhang
Department of General Surgery, The Affiliated Children's Hospital of Nanchang University, Nanchang, China
Correspondence
Zigang Cao, School of Life Sciences, Jinggangshan University, Ji'an 343009, China.
Email: [email protected]
Shouhua Zhang, Department of General Surgery, The Affiliated Children's Hospital of Nanchang University, Nanchang 330006, China.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Zigang Cao
Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, College of Life Sciences, Clinical Research Center of Affiliated Hospital of Jinggangshan University, Jinggangshan University, Ji'an, China
Correspondence
Zigang Cao, School of Life Sciences, Jinggangshan University, Ji'an 343009, China.
Email: [email protected]
Shouhua Zhang, Department of General Surgery, The Affiliated Children's Hospital of Nanchang University, Nanchang 330006, China.
Email: [email protected]
Search for more papers by this authorLing Huang and Zhipeng Wang should be considered joint first author.
Abstract
Apatinib, a small-molecule VEGFR2-tyrosine kinase inhibitor, has shown potent anticancer activity in various clinical cancer treatments, but also different adverse reactions. Therefore, it is necessary to study its potential toxicity and working mechanism. We used zebrafish to investigate the effects of apatinib on the development of embryos. Zebrafish exposed to 2.5, 5, and 10 μM apatinib showed adverse effects such as decreased liver area, pericardial oedema, slow yolk absorption, bladder atrophy, and body length shortening. At the same time, it leads to abnormal liver tissue structure, liver function and related gene expression. Furthermore, after exposure to apatinib, oxidative stress levels were significantly elevated but liver developmental toxicity was effectively ameliorated with oxidative stress inhibitor treatment. Apatinib induces down-regulation of key target genes of Wnt signaling pathway in zebrafish, and it is found that Wnt activator can significantly rescue liver developmental defects. These results suggest that apatinib may induce zebrafish hepatotoxicity by inhibiting the Wnt signaling pathway and up-regulating oxidative stress, helping to strengthen our understanding of rational clinical application of apatinib.
CONFLICT OF INTEREST STATEMENT
The authors declare no conflicts of interest.
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