Evaluation of the cardiotoxicity of Echinochrome A using human induced pluripotent stem cell-derived cardiac organoids.

Autor: Lee SJ; Center for Bio-Signal Research, Division of Advanced Predictive Research, Korea Institute of Toxicology (KIT), Daejeon 34114, Republic of Korea; Department of Physiology, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea., Kim E; Center for Bio-Signal Research, Division of Advanced Predictive Research, Korea Institute of Toxicology (KIT), Daejeon 34114, Republic of Korea., Jeong Y; Center for Bio-Signal Research, Division of Advanced Predictive Research, Korea Institute of Toxicology (KIT), Daejeon 34114, Republic of Korea., Youm JB; National Research Laboratory for Mitochondrial Signaling, Department of Physiology, Cardiovascular and Metabolic Disease Center, Inje University College of Medicine, Busan 47392, Republic of Korea., Kim HK; National Research Laboratory for Mitochondrial Signaling, Department of Physiology, Cardiovascular and Metabolic Disease Center, Inje University College of Medicine, Busan 47392, Republic of Korea., Han J; National Research Laboratory for Mitochondrial Signaling, Department of Physiology, Cardiovascular and Metabolic Disease Center, Inje University College of Medicine, Busan 47392, Republic of Korea., Vasileva EA; G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Vladivostok 690022, Russia., Mishchenko NP; G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Vladivostok 690022, Russia., Fedoreyev SA; G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Vladivostok 690022, Russia., Stonik VA; G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Vladivostok 690022, Russia., Kim SJ; Department of Physiology, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea. Electronic address: sjoonkim@snu.ac.kr., Lee HA; Center for Bio-Signal Research, Division of Advanced Predictive Research, Korea Institute of Toxicology (KIT), Daejeon 34114, Republic of Korea. Electronic address: vanessa@kitox.re.kr.
Jazyk: angličtina
Zdroj: Ecotoxicology and environmental safety [Ecotoxicol Environ Saf] 2024 Dec 06; Vol. 289, pp. 117489. Date of Electronic Publication: 2024 Dec 06.
DOI: 10.1016/j.ecoenv.2024.117489
Abstrakt: Echinochrome A (EchA), a marine-derived natural product, has shown promise in treating cardiovascular and inflammatory diseases due to its antioxidant and anti-inflammatory properties. However, its cardiac safety remains underexplored. In this study, we utilized human induced pluripotent stem cell-derived cardiac organoids (hCOs) to validate their ability to model the cardiac safety profile of EchA in a human-relevant system. While EchA's therapeutic effects have been reported, prior studies have not evaluated its cardiotoxicity or arrhythmogenic potential in a high-fidelity 3D human cardiac model. The hCOs, characterized by expression of key cardiac markers (cTnT) and functional ion channels (Cav1.2, Nav1.5, hERG), exhibited structural and electrophysiological properties reflective of human cardiac physiology. Using multi-electrode array (MEA) analysis, we assessed the effects of EchA at concentrations ranging from 0.1 to 30 µM on electrophysiological parameters, including beat period, field potential amplitude, field potential duration, and spike slope. EchA treatment induced no significant changes in these parameters, confirming its non-toxic electrophysiological profile. Cellular viability and lactate dehydrogenase (LDH) assays revealed no cytotoxic effects of EchA across tested concentrations. Contractility assays further demonstrated that EchA did not affect contraction velocity, relaxation velocity, or time to 50 % maximal contraction and relaxation. This study fills a critical gap and highlights the translational relevance of hCOs for cardiotoxicity assessment, demonstrating EchA's cardiac safety and supporting its potential therapeutic and environmental applications.
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 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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