Dim light at night induces cardiac injury in zebrafish embryos via disrupted chloride homeostasis

  • iScience. 2026 Jun 3;29(6):115796. doi: 10.1016/j.isci.2026.115796.
Risi Chen  1  2 ,  Ying Zeng  3 ,  Meixin Min  1 ,  Ke Xu  1 ,  Jia Wang  1 ,  Tingting Liu  1  2 ,  Yan Zhao  1  2 ,  Weixin Zhang  1  2 ,  Shuting Cheng  4 ,  Yiyue Zhang  5 ,  Chunru Wang  6 ,  Dan Deng  7 ,  Xiaoping Xiao  1  2
Affiliations
  • 1. Ganzhou Key Laboratory for Drug Screening and Discovery, School of Geography and Environmental Engineering, Gannan Normal University, Ganzhou 341000, China.
  • 2. Jiangxi Provincial Key Laboratory of Synthetic Pharmaceutical Chemistry, Gannan Normal University, Ganzhou 341000, China.
  • 3. Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, China.
  • 4. Health Ministry Key Laboratory of Chronobiology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China.
  • 5. Innovation Centre of Ministry of Education for Development and Diseases, School of Medicine, South China University of Technology, Guangzhou 510006, China.
  • 6. Beijing National Research Center for Molecular Sciences, Key Laboratory of Molecular Nanostructure and Nanotechnology, Institute of Chemistry, Chinese Academy of Science, Beijing 100190, China.
  • 7. Gannan Health Vocational College, Ganzhou 341000, China.
PMID: 42291255 DOI: 10.1016/j.isci.2026.115796
Abstract

Artificial light at night (ALAN) is an escalating environmental stressor linked to Cardiovascular Disease, yet its underlying mechanisms remain poorly understood. Here, we investigate the molecular basis of this pathology using zebrafish embryos for mechanistic discovery and murine models for translational validation under a chronic dim- light- at -night (dLAN) paradigm. dLAN exposure induced cardiac injury characterized by pericardial edema and hemodynamic impairment. Transcriptomic profiling revealed dysregulation of inflammatory and oxidative stress pathways, accompanied by marked suppression of the calcium-activated Chloride Channel accessory protein zclca1. Genetic knockdown of zclca1 recapitulated core dLAN pathologies, while pharmacological intervention with the chloride-modulating diuretic bumetanide reversed cardiac dysfunction in both species. These findings identify a conserved "dLAN-CLCA-chloride-cardiac injury" axis, wherein light pollution disrupts chloride homeostasis to drive cardiac pathology, suggesting that chloride modulation may represent a potential therapeutic strategy for mitigating light pollution-induced cardiovascular injury.

Keywords
environmental health; molecular biology.
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