Investigation of verapamil-induced cardiorenal dysfunction and compensatory ion regulation in zebrafish embryos.

Autor: Horng JL; Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan., Hsiao BY; Division of Cardiology and Cardiovascular Research Center, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 11031, Taiwan; Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan; Taipei Heart Institute, Taipei Medical University, Taipei 11031, Taiwan., Lin WT; Affiliated Senior High School of National Taiwan Normal University, Taipei 10658, Taiwan., Lin TT; Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan., Chang CY; Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan., Lin LY; Department of Life Science, National Taiwan Normal University, Taipei 11677, Taiwan. Electronic address: linly@ntnu.edu.tw.
Jazyk: angličtina
Zdroj: Comparative biochemistry and physiology. Toxicology & pharmacology : CBP [Comp Biochem Physiol C Toxicol Pharmacol] 2024 Oct; Vol. 284, pp. 109980. Date of Electronic Publication: 2024 Jul 20.
DOI: 10.1016/j.cbpc.2024.109980
Abstrakt: The purpose of the present study was to investigate the development of verapamil-induced cardiorenal failure and the response of epidermal ionocytes in zebrafish embryos to this syndrome. Zebrafish embryos were exposed to verapamil for 24 h at different developmental stages (48, 72, and 96 h post-fertilization). The exposure resulted in the generation of edema in the pericardial and yolk sac regions, with more-pronounced effects observed in later-stage embryos. Cardiac parameters showed a suppressed heart rate at all stages, with a more-significant effect appearing in later stages. Verapamil also affected cardiac parameters including the end-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF), and cardiac output (CO), indicating negative overall effects on cardiac performance. mRNA levels of heart failure markers (nppa and nppb genes) were upregulated in verapamil-exposed embryos at all stages. Renal function was impaired as FITC-dextran excretion was suppressed. A whole-embryo ion content analysis revealed significant increases in sodium and calcium contents in verapamil-exposed embryos. The density of epidermal ionocytes increased, and the apical membrane of ionocytes was enlarged, indicating upregulation of ion uptake. In addition, mRNA levels of several ion transporter genes (rhcg1, slc9a3, atp6v1a, atp2b1a, trpv6, and slc12a10.2) were significantly upregulated in verapamil-exposed embryos. In summary, prolonged exposure to verapamil can induce cardiorenal failure which triggers compensatory upregulation of ionocytes in zebrafish embryos.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier Inc.)
Databáze: MEDLINE
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