2. Academic Validation
  3. Dimethyl fumarate induces cardiac developmental toxicity in zebrafish via down-regulation of oxidative stress

Dimethyl fumarate induces cardiac developmental toxicity in zebrafish via down-regulation of oxidative stress

  • Toxicology. 2024 Jan 23:153735. doi: 10.1016/j.tox.2024.153735.
Mengqi Wan 1,  Jiejun Liu 2,  Dou Yang 2,  Zhonghao Xiao 2,  Xue Li 2,  Jieping Liu 2,  Ling Huang 2,  Fasheng Liu 2,  Shouhua Zhang 3,  Qiang Tao 3,  Juhua Xiao 4,  Zigang Cao 5
Affiliations

Affiliations

  • 1 Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Ji'an, Jiangxi, China; Jiangxi Key Laboratory of Developmental Biology of Organs, College of Life Sciences, Clinical Research Center of Affiliated Hospital of Jinggangshan University, Jinggangshan University, Ji'an, 343009 Jiangxi, China; Department of General Surgery,The Affiliated Children's Hospital of Nanchang University, Nanchang, Jiangxi; 330006,China.
  • 2 Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Ji'an, Jiangxi, China; Jiangxi Key Laboratory of Developmental Biology of Organs, College of Life Sciences, Clinical Research Center of Affiliated Hospital of Jinggangshan University, Jinggangshan University, Ji'an, 343009 Jiangxi, China.
  • 3 Department of General Surgery,The Affiliated Children's Hospital of Nanchang University, Nanchang, Jiangxi; 330006,China.
  • 4 Department of Ultrasound, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, 330006, Jiangxi, China.
  • 5 Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Ji'an, Jiangxi, China; Jiangxi Key Laboratory of Developmental Biology of Organs, College of Life Sciences, Clinical Research Center of Affiliated Hospital of Jinggangshan University, Jinggangshan University, Ji'an, 343009 Jiangxi, China. Electronic address: [email protected].
PMID: 38272385 DOI: 10.1016/j.tox.2024.153735
Abstract

Dimethyl fumarate (DMF) is an immunosuppressant commonly used to treat multiple sclerosis and other autoimmune diseases. Despite known side effects such as lymphopenia, the effect of DMF on cardiac development remains unclear. To assess this, we used zebrafish to evaluate the cardiac developmental toxicity of DMF. Our study showed that DMF reduced the survival rate of zebrafish embryos, with those exposed to 1, 1.3, and 1.6mg/L exhibiting heart rate reduction, shortened body length, delayed yolk sac absorption, pericardial edema, increased distance from sinus venous to bulbus arteriosus, and separation of cardiomyocytes and endocardial cells at 72 hpf. Heart development-related genes showed disorder, apoptosis-related genes were up-regulated, and the oxidative stress response was down-regulated. Treatment with cysteamine ameliorated the heart development defects. Our study demonstrates that DMF induces cardiac developmental toxicity in zebrafish, possibly by down-regulating oxidative stress responses. This study provides a certain research basis for further study of DMF-induced cardiac developmental toxicity, and provides some experimental evidence for future clinical application and study of DMF.

Keywords

apoptosis; cardiotoxicity; dimethyl fumarate; oxidative stress.

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