斑马鱼的卡博桑提尼布诱导的胀代表了一种不良影响,其特点是淋巴血管和功能缺陷
Raghavender Medishetti1,2, Mallikarjuna Rao C3, Kiranam Chatti1
1Center for Innovation in Molecular and Pharmaceutical Sciences, Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, Hyderabad, Telangana, India.
Journal of biochemical and molecular toxicology
|June 19, 2023
概括
氨酸激酶抑制剂 (TKIs) 可以引起,特别是像卡博桑提尼布这样的VEGFR抑制剂. 斑马鱼研究显示血管和功能障碍是这种TKI副作用的可能原因.
科学领域:
- 药理学 药理学 是一个学科.
- 发展生物学 发展生物学
- 毒理学 毒理学 毒理学
背景情况:
- 氨酸激酶抑制剂 (TKI) 是关键的向癌症疗法.
- 开发新的技术知识和克服现有技术知识的局限性至关重要.
- 需要可访问的动物模型来评估TKI的不良影响.
研究的目的:
- 评估22个FDA批准的TCI使用斑马鱼幼虫的不良影响.
- 调查卡博桑提尼布诱导的胀及其潜在机制.
- 确定TKI诱导的的潜在临床影响.
主要方法:
- 斑马鱼幼虫暴露于22个TKI.
- 评估死亡率,发育和形态异常.
- 进行了与血管和功能相关的基因表达的分子分析.
主要成果:
- 胀是VEGFR抑制剂,特别是卡博桑提尼布在非致死剂量时的突出影响.
- 卡博桑提尼布暴露导致血管损失,淋巴缺陷和功能抑制.
- 观察到对VEGFR,prox1a,sox18,nephrin和podocin基因的下调.
结论:
- edem 是 cabozantinib 的一种新型表型效应,与血管和功能障碍有关.
- 这些发现表明,使用卡博桑提尼布和其他VEGFR抑制剂可能存在的临床风险.
- 斑马鱼幼虫作为TKI毒性查的宝贵模型.
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