Evaluation of the cardiotoxicity potential of bisphenol analogues in human induced pluripotent stem cells derived cardiomyocytes
The importance of evaluating the cardiotoxicity potential of common chemicals as well as new drugs is increasing as a result of the development of animal alternative test methods using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). Bisphenol A (BPA), which is used as a main m...
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Format: | Article |
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Elsevier
2024-03-01
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Series: | Ecotoxicology and Environmental Safety |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651324001830 |
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author | Seul-Gi Lee Gyeong-Eun Song Jin Seok Jin Kim Min Woo Kim Jooeon Rhee Shinhye Park Kyu Sik Jeong Suemin Lee Yun Hyeong Lee Youngin Jeong Hyung Min Chung C-Yoon Kim |
author_facet | Seul-Gi Lee Gyeong-Eun Song Jin Seok Jin Kim Min Woo Kim Jooeon Rhee Shinhye Park Kyu Sik Jeong Suemin Lee Yun Hyeong Lee Youngin Jeong Hyung Min Chung C-Yoon Kim |
author_sort | Seul-Gi Lee |
collection | DOAJ |
description | The importance of evaluating the cardiotoxicity potential of common chemicals as well as new drugs is increasing as a result of the development of animal alternative test methods using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). Bisphenol A (BPA), which is used as a main material in plastics, is known as an endocrine-disrupting chemical, and recently reported to cause cardiotoxicity through inhibition of ion channels in CMs even with acute exposure. Accordingly, the need for the development of alternatives to BPA has been highlighted, and structural analogues including bisphenol AF, C, E, F, and S have been developed. However, cardiotoxicity data for analogues of bisphenol are not well known. In this study, in order to evaluate the cardiotoxicity potential of analogues, including BPA, a survival test of hiPSC-CMs and a dual-cardiotoxicity evaluation based on a multi-electrode array were performed. Acute exposure to all bisphenol analogues did not affect survival rate, but spike amplitude, beat period, and field potential duration were decreased in a dose-dependent manner in most of the bisphenols except bisphenol S. In addition, bisphenols, except for bisphenol S, reduced the contractile force of hiPSC-CMs and resulted in beating arrest at high doses. Taken together, it can be suggested that the developed bisphenol analogues could cause cardiotoxicity even with acute exposure, and it is considered that the application of the MEA-based dual-cardiotoxicity evaluation method can be an effective help in the development of safe alternatives. |
first_indexed | 2024-03-07T23:07:13Z |
format | Article |
id | doaj.art-82f84cd4f0f74fca833454a13566a9f5 |
institution | Directory Open Access Journal |
issn | 0147-6513 |
language | English |
last_indexed | 2024-03-07T23:07:13Z |
publishDate | 2024-03-01 |
publisher | Elsevier |
record_format | Article |
series | Ecotoxicology and Environmental Safety |
spelling | doaj.art-82f84cd4f0f74fca833454a13566a9f52024-02-22T04:51:41ZengElsevierEcotoxicology and Environmental Safety0147-65132024-03-01272116108Evaluation of the cardiotoxicity potential of bisphenol analogues in human induced pluripotent stem cells derived cardiomyocytesSeul-Gi Lee0Gyeong-Eun Song1Jin Seok2Jin Kim3Min Woo Kim4Jooeon Rhee5Shinhye Park6Kyu Sik Jeong7Suemin Lee8Yun Hyeong Lee9Youngin Jeong10Hyung Min Chung11C-Yoon Kim12Department of Stem Cell Biology, School of Medicine, Konkuk University, 120 Neungdong-Ro, Gwangjin-Gu, Seoul 05029, Republic of Korea; College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of KoreaCollege of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of KoreaCollege of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of KoreaCollege of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of KoreaCollege of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of KoreaCollege of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of KoreaCollege of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of KoreaCollege of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of KoreaCollege of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of KoreaCollege of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of KoreaCollege of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of KoreaDepartment of Stem Cell Biology, School of Medicine, Konkuk University, 120 Neungdong-Ro, Gwangjin-Gu, Seoul 05029, Republic of Korea; Miraecell Bio Co. Ltd., Seoul 04795, Republic of KoreaCollege of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of Korea; Corresponding author.The importance of evaluating the cardiotoxicity potential of common chemicals as well as new drugs is increasing as a result of the development of animal alternative test methods using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). Bisphenol A (BPA), which is used as a main material in plastics, is known as an endocrine-disrupting chemical, and recently reported to cause cardiotoxicity through inhibition of ion channels in CMs even with acute exposure. Accordingly, the need for the development of alternatives to BPA has been highlighted, and structural analogues including bisphenol AF, C, E, F, and S have been developed. However, cardiotoxicity data for analogues of bisphenol are not well known. In this study, in order to evaluate the cardiotoxicity potential of analogues, including BPA, a survival test of hiPSC-CMs and a dual-cardiotoxicity evaluation based on a multi-electrode array were performed. Acute exposure to all bisphenol analogues did not affect survival rate, but spike amplitude, beat period, and field potential duration were decreased in a dose-dependent manner in most of the bisphenols except bisphenol S. In addition, bisphenols, except for bisphenol S, reduced the contractile force of hiPSC-CMs and resulted in beating arrest at high doses. Taken together, it can be suggested that the developed bisphenol analogues could cause cardiotoxicity even with acute exposure, and it is considered that the application of the MEA-based dual-cardiotoxicity evaluation method can be an effective help in the development of safe alternatives.http://www.sciencedirect.com/science/article/pii/S0147651324001830Bisphenol ABisphenol analoguesCardiotoxicityField potentialContractility |
spellingShingle | Seul-Gi Lee Gyeong-Eun Song Jin Seok Jin Kim Min Woo Kim Jooeon Rhee Shinhye Park Kyu Sik Jeong Suemin Lee Yun Hyeong Lee Youngin Jeong Hyung Min Chung C-Yoon Kim Evaluation of the cardiotoxicity potential of bisphenol analogues in human induced pluripotent stem cells derived cardiomyocytes Ecotoxicology and Environmental Safety Bisphenol A Bisphenol analogues Cardiotoxicity Field potential Contractility |
title | Evaluation of the cardiotoxicity potential of bisphenol analogues in human induced pluripotent stem cells derived cardiomyocytes |
title_full | Evaluation of the cardiotoxicity potential of bisphenol analogues in human induced pluripotent stem cells derived cardiomyocytes |
title_fullStr | Evaluation of the cardiotoxicity potential of bisphenol analogues in human induced pluripotent stem cells derived cardiomyocytes |
title_full_unstemmed | Evaluation of the cardiotoxicity potential of bisphenol analogues in human induced pluripotent stem cells derived cardiomyocytes |
title_short | Evaluation of the cardiotoxicity potential of bisphenol analogues in human induced pluripotent stem cells derived cardiomyocytes |
title_sort | evaluation of the cardiotoxicity potential of bisphenol analogues in human induced pluripotent stem cells derived cardiomyocytes |
topic | Bisphenol A Bisphenol analogues Cardiotoxicity Field potential Contractility |
url | http://www.sciencedirect.com/science/article/pii/S0147651324001830 |
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