Evaluation of the cardiotoxicity of Echinochrome A using human induced pluripotent stem cell-derived cardiac organoids
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-d...
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Elsevier
2025-01-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651324015653 |
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| author | Su-Jin Lee Eunji Kim Yeeun Jeong Jae Boum Youm Hyoung Kyu Kim Jin Han Elena A. Vasileva Natalia P. Mishchenko Sergey A. Fedoreyev Valentin A. Stonik Sung Joon Kim Hyang-Ae Lee |
| author_facet | Su-Jin Lee Eunji Kim Yeeun Jeong Jae Boum Youm Hyoung Kyu Kim Jin Han Elena A. Vasileva Natalia P. Mishchenko Sergey A. Fedoreyev Valentin A. Stonik Sung Joon Kim Hyang-Ae Lee |
| author_sort | Su-Jin Lee |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-1395581cc957421585441c41c182ec15 |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-1395581cc957421585441c41c182ec152025-01-23T05:25:45ZengElsevierEcotoxicology and Environmental Safety0147-65132025-01-01289117489Evaluation of the cardiotoxicity of Echinochrome A using human induced pluripotent stem cell-derived cardiac organoidsSu-Jin Lee0Eunji Kim1Yeeun Jeong2Jae Boum Youm3Hyoung Kyu Kim4Jin Han5Elena A. Vasileva6Natalia P. Mishchenko7Sergey A. Fedoreyev8Valentin A. Stonik9Sung Joon Kim10Hyang-Ae Lee11Center 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 KoreaCenter for Bio-Signal Research, Division of Advanced Predictive Research, Korea Institute of Toxicology (KIT), Daejeon 34114, Republic of KoreaCenter for Bio-Signal Research, Division of Advanced Predictive Research, Korea Institute of Toxicology (KIT), Daejeon 34114, Republic of KoreaNational Research Laboratory for Mitochondrial Signaling, Department of Physiology, Cardiovascular and Metabolic Disease Center, Inje University College of Medicine, Busan 47392, Republic of KoreaNational Research Laboratory for Mitochondrial Signaling, Department of Physiology, Cardiovascular and Metabolic Disease Center, Inje University College of Medicine, Busan 47392, Republic of KoreaNational Research Laboratory for Mitochondrial Signaling, Department of Physiology, Cardiovascular and Metabolic Disease Center, Inje University College of Medicine, Busan 47392, Republic of KoreaG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Vladivostok 690022, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Vladivostok 690022, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Vladivostok 690022, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Vladivostok 690022, RussiaDepartment of Physiology, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Co-corresponding author.Center for Bio-Signal Research, Division of Advanced Predictive Research, Korea Institute of Toxicology (KIT), Daejeon 34114, Republic of Korea; Correspondence to: Center for Bio-Signal Research, Korea Institute of Toxicology, 141 Gajeong-ro, Yuseong-gu, Daejeon 34114, Republic of Korea.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.http://www.sciencedirect.com/science/article/pii/S0147651324015653Echinochrome AEchACardiac organoidsElectrohysiologyCardiac safety |
| spellingShingle | Su-Jin Lee Eunji Kim Yeeun Jeong Jae Boum Youm Hyoung Kyu Kim Jin Han Elena A. Vasileva Natalia P. Mishchenko Sergey A. Fedoreyev Valentin A. Stonik Sung Joon Kim Hyang-Ae Lee Evaluation of the cardiotoxicity of Echinochrome A using human induced pluripotent stem cell-derived cardiac organoids Ecotoxicology and Environmental Safety Echinochrome A EchA Cardiac organoids Electrohysiology Cardiac safety |
| title | Evaluation of the cardiotoxicity of Echinochrome A using human induced pluripotent stem cell-derived cardiac organoids |
| title_full | Evaluation of the cardiotoxicity of Echinochrome A using human induced pluripotent stem cell-derived cardiac organoids |
| title_fullStr | Evaluation of the cardiotoxicity of Echinochrome A using human induced pluripotent stem cell-derived cardiac organoids |
| title_full_unstemmed | Evaluation of the cardiotoxicity of Echinochrome A using human induced pluripotent stem cell-derived cardiac organoids |
| title_short | Evaluation of the cardiotoxicity of Echinochrome A using human induced pluripotent stem cell-derived cardiac organoids |
| title_sort | evaluation of the cardiotoxicity of echinochrome a using human induced pluripotent stem cell derived cardiac organoids |
| topic | Echinochrome A EchA Cardiac organoids Electrohysiology Cardiac safety |
| url | http://www.sciencedirect.com/science/article/pii/S0147651324015653 |
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