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2025/02/10

Development of zebrafish-based oncocardionephrology

Development of zebrafish-based oncocardionephrology

Cardiotoxicity and nephrotoxicity caused by molecularly targeted cancer drugs have been observed in many clinical cases, but the mechanisms of each toxicity are often unknown at present. The interaction and integrated analysis of cardiotoxicity and nephrotoxicity are extremely difficult. Therefore, the need for oncocardionephrology has been advocated internationally. However, research models for simultaneous quantitative analysis of these cancer drug effects and cardionephrotoxicity mechanisms in the same individual are currently lacking, even globally. Historically, cardiorenal toxicity analyses have been conducted first in a small number of normal mammalian models. In addition, there has been great promise in human cell (organoid, iPS cell, ES cell, etc.) models. On the other hand, oncocardionephrology with zebrafish (Danio rerio) has taken the unique advantage of high-throughput in vivo screening, and the toxicity mechanisms of cancer therapy on cardiorenal function. To enable high-throughput in chemical/omics screening in oncocardionephrology using zebrafish, we have introduced fluorescent proteins into the heart and tubules of the transparent zebrafish MieKomachi103 (cmlc2:mRFP/enpep:GFP/nacre) was created. Furthermore, we established a live quantitative individual proteinuria analysis method using our originally developed ZMB741 (Chemical & Biomedical Imaging. 2024 May 31;2(11):755- 764.), a whole plasma protein binding dye that can be administered non-invasively. We will report on the latest research developments with this new zebrafish oncocardionephrology model.