以大型蚤为临床前模型评估癌症化疗药物的心脏毒性

Qudrathulla Khan Quadri Mohammed, Rama Krishna Kancha
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引用次数: 0

摘要

癌症治疗后的主要问题之一是心脏毒性。因此,在临床前阶段预测癌症化疗药物的潜在心脏毒性非常重要。目前的心脏毒性测试模型包括细胞培养模型或啮齿类动物模型。我们开发了一种简单的无脊椎动物模型,用于快速筛查癌症化疗药物的心脏毒性。大型水蚤(水蚤,一种甲壳类动物)有一个透明的身体和一个大的肌源性心脏,可以很容易地在显微镜下进行监测。利用这一模型,我们之前描述了几种被批准用于治疗多种癌症的激酶抑制剂的心脏毒性比较。在这篇文章中,我们将分步描述评估 D. magna 心率和存活率的方案,并提供相关的故障排除信息。基本方案 1:大型蚤的培养和维护基本方案 2:评估水蚤心率的实验设计基本方案 3:药物暴露对水蚤存活的长期影响
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Evaluation of Cardiotoxicity of Cancer Chemotherapeutics Using Daphnia magna as a Preclinical Model

One of the major concerns following cancer treatment is cardiotoxicity. Therefore, it is important to predict potential cardiotoxicity of cancer chemotherapeutics at the preclinical phase. Current models of cardiotoxicity testing involve either cell culture models or rodent models. We developed a simple invertebrate animal model for rapid screening of cardiotoxicity of cancer chemotherapeutics. Daphnia magna (water flea, a crustacean) has a transparent body and a large myogenic heart that can be easily monitored under a microscope. Using this model, we have previously described comparative cardiotoxicity of several kinase inhibitors that were approved for the treatment of multiple cancers. In this article, we describe the step-wise protocols for evaluating the heart rate and survival of D. magna with relevant information on troubleshooting. © 2024 Wiley Periodicals LLC.

Basic Protocol 1: Culturing and maintenance of D. magna

Basic Protocol 2: Experimental design for evaluating heart rate of Daphnia

Basic Protocol 3: Long-term effect on Daphnia survival upon drug exposure

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