Evidence mapPaperPMID 41968204Full record

ArticleCardiovascular toxicology2026

Zebrafish Model Reveals Early Electrocardiographic and Molecular Signatures of Doxorubicin-Induced Cardiotoxicity.

Zih-Yin Lai, Chi-Ying Lee, Yu-Ching Chiu, Chia-Hung Lin, Chung-Chi Yang, Chia-Chia Ho, Lawrence Yu-Min Liu, Yung-Jen Chuang

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Article in Cardiovascular toxicology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Zih-Yin Lai *School of Medicine, National Tsing Hua University, Hsinchu, 300044, Taiwan, R.O.C.
Chi-Ying Lee *School of Medicine, National Tsing Hua University, Hsinchu, 300044, Taiwan, R.O.C.
Yu-Ching ChiuSchool of Medicine, National Tsing Hua University, Hsinchu, 300044, Taiwan, R.O.C.
Chia-Hung LinSchool of Medicine, National Tsing Hua University, Hsinchu, 300044, Taiwan, R.O.C.
Chung-Chi YangSchool of Medicine, National Tsing Hua University, Hsinchu, 300044, Taiwan, R.O.C.
Chia-Chia HoSchool of Medicine, National Tsing Hua University, Hsinchu, 300044, Taiwan, R.O.C.
Lawrence Yu-Min LiuDivision of Cardiology, Department of Internal Medicine, Hsinchu MacKay Memorial Hospital, Hsinchu, 300044, Taiwan, R.O.C.. drlawrenceliu@gmail.com.
Yung-Jen ChuangSchool of Medicine, National Tsing Hua University, Hsinchu, 300044, Taiwan, R.O.C.. yjchuang@life.nthu.edu.tw.

Funding

Hsinchu MacKay Memorial Hospital MMH-HB-11402National Science and Technology Council NSTC 113-2314-B-195-008-
6 · The paper itself

Abstract

Doxorubicin (DOX) is a highly effective anthracycline widely used in cancer therapy but limited by its dose-dependent cardiotoxicity, which may result in arrhythmia, dilated cardiomyopathy, and heart failure. Conventional surveillance tools, including echocardiography and serum biomarkers, often identify injury only after substantial cardiac dysfunction has occurred. This underscores the need for early markers with mechanistic relevance. In this study, we developed an integrated zebrafish platform combining pathophysiological evaluation, electrocardiography (ECG), and transcriptomic profiling to establish a novel approach for early detection of DOX-induced cardiotoxicity (DIC). Consistent with human and mammalian models, DOX administration in adult zebrafish resulted in ventricular enlargement, myocardial fiber disarray, and elevated troponin I levels. ECG recordings revealed dose-dependent conduction disturbances, notably progressive PR interval and QRS prolongation, with P wave widening at higher doses. These findings identify the PR interval as a sensitive, early index of conduction impairment in the zebrafish DIC model, consistent with clinical reports linking PR prolongation to adverse outcomes. RNA sequencing further identified transcriptional pathways associated with conduction delay, with dysregulation of sodium channels (scn5lab, scn1lab), gap junction proteins (cx43, cx40.8), and transcriptional regulators (nkx2.5, tbx family). Notably, scn1lab expression declined progressively, cx43 and nkx2.5 were upregulated, showing temporal changes that co-occurred with the observed ECG and structural phenotypes. Together, these results support adult zebrafish as a scalable platform for cardiotoxicity screening and highlight PR interval prolongation as an early electrophysiological marker of DOX-associated conduction disturbance. The transcriptomic signatures are presented as correlative, hypothesis-generating candidates relevant to cardiac conduction and remodeling.

Indexed as

Action PotentialsAntibiotics, AntineoplasticArrhythmias, CardiacDoxorubicinElectrocardiographyHeart DiseasesHeart RateMyocytes, CardiacTranscriptomeAnimalsAnimals, Genetically ModifiedCardiotoxicityDisease Models, AnimalDose-Response Relationship, DrugGene Expression ProfilingPhenotypeAntibiotics, AntineoplasticDoxorubicinZebrafish ProteinsCardiotoxicityDoxorubicinElectrocardiographyPR intervalZebrafish

Identifiers

PMID41968204
PMCPMC13070985

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.