2. Academic Validation
  3. The influence of sunitinib and sorafenib, two tyrosine kinase inhibitors, on development and thyroid system in zebrafish larvae

The influence of sunitinib and sorafenib, two tyrosine kinase inhibitors, on development and thyroid system in zebrafish larvae

  • Chemosphere. 2022 Dec;308(Pt 2):136354. doi: 10.1016/j.chemosphere.2022.136354.
Gang Wei 1,  Cao-Xu Zhang 2,  Yu Jing 2,  Xia Chen 3,  Huai-Dong Song 2,  Liu Yang 4
Affiliations

Affiliations

  • 1 The Core Laboratory in Medical Center of Clinical Research, Department of Molecular Diagnostics & Endocrinology, Shanghai Ninth People's Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China; Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province, Hangzhou, 310015, China; Beijing Key Laboratory of Diabetes Research and Care, Department of Endocrinology, Beijing Diabetes Institute, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China. Electronic address: gangwei_2013@163.com.
  • 2 The Core Laboratory in Medical Center of Clinical Research, Department of Molecular Diagnostics & Endocrinology, Shanghai Ninth People's Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
  • 3 Department of Endocrinology, Shanghai Gongli Hospital, Shanghai, 200135, China.
  • 4 The Core Laboratory in Medical Center of Clinical Research, Department of Molecular Diagnostics & Endocrinology, Shanghai Ninth People's Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China. Electronic address: 18210655830@sina.cn.
PMID: 36087734 DOI: 10.1016/j.chemosphere.2022.136354
Abstract

Recently, the potential toxic effects of various pharmaceuticals on the thyroid endocrine system have raised considerable concerns. In this study, we evaluated the adverse effects of sorafenib and sunitinib, two widely used anti-tumor drugs, on the developmental toxicities and thyroid endocrine disruption by using zebrafish (Danio rerio) model. Zebrafish embryos/larvae were exposed to different contentions (0, 10, 50 and 100 nM) of sorafenib and sunitinib for 96 hpf. The results revealed that waterborne exposure to sorafenib and sunitinib exhibited remarkable toxic effects on the survival and development in zebrafish embryos/larvae, which was accompanied by obvious disturbances of thyroid endocrine system (e.g., decreased T3 and T4 content, increased TSH content) and genes' transcription changes within the hypothalamus-pituitary-thyroid (HPT) axis. In addition, we verified a strikingly abnormal thyroid gland organogenesis in zebrafish larvae in response to sorafenib and sunitinib, by assessing the development of thyroid follicles using the WISH staining of tg, the Tg (tg:GFP) zebrafish transgenic line, and histopathological analysis. Taken together, our results indicated sorafenib and sunitinib exposure could induce obvious developmental toxicities and thyroid function disruption in zebrafish embryos/larvae, which might involve a regulatory mechanism, at least in part, by destroying the thyroid follicle structure, and by disturbing the balance of the HPT axis.

Keywords

Anti-tumor drug; Danio rerio; Hypothalamus-pituitary-thyroid axis; Thyroid disruption.

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