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Toxicity Evaluation and Biomarker Selection with Validated Reference Gene in Embryonic Zebrafish Exposed to Mitoxantrone

文献类型： 外文期刊

作者： Liu, Lili 1 ; Zhu, Hua 1 ; Yan, Yanchun 2 ; Lv, Peng 2 ; Wu, Wei 2 ;

作者机构： 1.Beijing Fisheries Res Inst, Beijing Key Lab Fishery Biotechnol, Beijing 100068, Peoples R China

2.Chinese Acad Agr Sci, Grad Sch, Beijing 100081, Peoples R China

关键词： reference genes; stability evaluation; zebrafish embryos; mitoxantrone; toxicity evaluation; biomarker selection

期刊名称：INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES （ 影响因子：5.923； 五年影响因子：6.132 ）

ISSN： 1422-0067

年卷期： 2018 年 19 卷 11 期

页码：

收录情况： SCI

摘要： Notwithstanding the widespread use and promising clinical value of chemotherapy, the pharmacokinetics, toxicology, and mechanism of mitoxantrone remains unclear. To promote the clinical value in the treatment of human diseases and the exploration of potential subtle effects of mitoxantrone, zebrafish embryos were employed to evaluate toxicity with validated reference genes based on independent stability evaluation programs. The most stable and recommended reference gene was gapdh, followed by tub1b, for the 48 h post fertilization (hpf) zebrafish embryo mitoxantrone test, while both eef1a1l1 and rpl13 were recommended as reference genes for the 96 hpf zebrafish embryo mitoxantrone test. With gapdh as an internal control, we analyzed the mRNA levels of representative hepatotoxicity biomarkers, including fabp10a, gclc, gsr, nqo1, cardiotoxicity biomarker erg, and neurotoxicity biomarker gfap in the 48 hpf embryo mitoxantrone test. The mRNA levels of gclc, gsr, and gfap increased significantly in 10 and 50 g/L mitoxantrone-treated 48 hpf embryos, while the transcript levels of fabp10a decreased in a dose-dependent manner, indicating that mitoxantrone induced hepatotoxicity and neurotoxicity. Liver hematoxylin-eosin staining and the spontaneous movement of embryos confirmed the results. Thus, the present research suggests that mitoxantrone induces toxicity during the development of the liver and nervous system in zebrafish embryos and that fabp10a is recommended as a potential biomarker for hepatotoxicity in zebrafish embryos. Additionally, gapdh is proposed as a reference gene for the 48 hpf zebrafish embryo mitoxantrone toxicity test, while eef1a1l1 and rpl13 are proposed as that for the 96 hpf test.

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[1]Toxicity Evaluation and Biomarker Selection with Validated Reference Gene in Embryonic Zebrafish Exposed to Mitoxantrone. Liu, Lili,Zhu, Hua,Liu, Lili,Yan, Yanchun,Lv, Peng,Wu, Wei. 2018

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