Enantioselective toxicity of (S)-amlodipine towards zebrafish embryos: Abnormal ocular development, cardiac dysfunction, and malformed intersegmental vessels
Amlodipine (AM), widely used for the treatment of hypertension and angina, consists of two enantiomers: (S)-AM and (R)-AM. The extensive use of this medication has raised concerns regarding environmental contamination, but the enantioselective toxicity of AM in aquatic organisms has not been adequat...
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Elsevier
2025-06-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325006517 |
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| author | Chaeeun Kim Donghyeon Kim Sung-Eun Lee |
| author_facet | Chaeeun Kim Donghyeon Kim Sung-Eun Lee |
| author_sort | Chaeeun Kim |
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| description | Amlodipine (AM), widely used for the treatment of hypertension and angina, consists of two enantiomers: (S)-AM and (R)-AM. The extensive use of this medication has raised concerns regarding environmental contamination, but the enantioselective toxicity of AM in aquatic organisms has not been adequately investigated. This study aimed to examine the enantioselective toxicity of AM using zebrafish (Danio rerio) embryos, focusing on acute toxicity and developmental toxicity. Neither enantiomer exhibited acute toxicity at the tested concentrations (0.25–20 mg/L). With respect to ocular development, (R)-AM reduced eye volume at the highest tested concentration. The lens-to-eye volume ratio showed a significant increase in embryos treated with both enantiomers compared to the control. Enantioselective toxicity was evident in cardiac function, as (S)-AM-induced heart dysfunction, despite both enantiomers displaying similar patterns of heart development-related gene expression. Severe defects in ISV formation were observed in both (S)-AM and (R)-AM treatments, indicating that AM exposure may result in abnormal blood vessel formation in other fish. Metabolomic analysis indicated that exposure to either enantiomer led to the upregulation of most metabolic pathways, except for starch and sucrose metabolism. Further research needs to confirm enantioselective toxicity under chronic conditions at environmentally relevant concentrations of AM. |
| format | Article |
| id | doaj-art-a15fd524fff14de2b4d77af91495cc2c |
| institution | OA Journals |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
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| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-a15fd524fff14de2b4d77af91495cc2c2025-08-20T01:52:42ZengElsevierEcotoxicology and Environmental Safety0147-65132025-06-0129811831510.1016/j.ecoenv.2025.118315Enantioselective toxicity of (S)-amlodipine towards zebrafish embryos: Abnormal ocular development, cardiac dysfunction, and malformed intersegmental vesselsChaeeun Kim0Donghyeon Kim1Sung-Eun Lee2Department of Applied Biosciences, Kyungpook National University, Daegu 41566, Republic of KoreaDepartment of Applied Biosciences, Kyungpook National University, Daegu 41566, Republic of KoreaDepartment of Applied Biosciences, Kyungpook National University, Daegu 41566, Republic of Korea; Department of Integrative Biology, Kyungpook National University, Daegu 41566, Republic of Korea; Corresponding author at: Department of Applied Biosciences, Kyungpook National University, Daegu 41566, Republic of Korea.Amlodipine (AM), widely used for the treatment of hypertension and angina, consists of two enantiomers: (S)-AM and (R)-AM. The extensive use of this medication has raised concerns regarding environmental contamination, but the enantioselective toxicity of AM in aquatic organisms has not been adequately investigated. This study aimed to examine the enantioselective toxicity of AM using zebrafish (Danio rerio) embryos, focusing on acute toxicity and developmental toxicity. Neither enantiomer exhibited acute toxicity at the tested concentrations (0.25–20 mg/L). With respect to ocular development, (R)-AM reduced eye volume at the highest tested concentration. The lens-to-eye volume ratio showed a significant increase in embryos treated with both enantiomers compared to the control. Enantioselective toxicity was evident in cardiac function, as (S)-AM-induced heart dysfunction, despite both enantiomers displaying similar patterns of heart development-related gene expression. Severe defects in ISV formation were observed in both (S)-AM and (R)-AM treatments, indicating that AM exposure may result in abnormal blood vessel formation in other fish. Metabolomic analysis indicated that exposure to either enantiomer led to the upregulation of most metabolic pathways, except for starch and sucrose metabolism. Further research needs to confirm enantioselective toxicity under chronic conditions at environmentally relevant concentrations of AM.http://www.sciencedirect.com/science/article/pii/S0147651325006517EnantiomersAmlodipineEnantioselective toxicityAbnormal ocular developmentHeart dysfunction |
| spellingShingle | Chaeeun Kim Donghyeon Kim Sung-Eun Lee Enantioselective toxicity of (S)-amlodipine towards zebrafish embryos: Abnormal ocular development, cardiac dysfunction, and malformed intersegmental vessels Ecotoxicology and Environmental Safety Enantiomers Amlodipine Enantioselective toxicity Abnormal ocular development Heart dysfunction |
| title | Enantioselective toxicity of (S)-amlodipine towards zebrafish embryos: Abnormal ocular development, cardiac dysfunction, and malformed intersegmental vessels |
| title_full | Enantioselective toxicity of (S)-amlodipine towards zebrafish embryos: Abnormal ocular development, cardiac dysfunction, and malformed intersegmental vessels |
| title_fullStr | Enantioselective toxicity of (S)-amlodipine towards zebrafish embryos: Abnormal ocular development, cardiac dysfunction, and malformed intersegmental vessels |
| title_full_unstemmed | Enantioselective toxicity of (S)-amlodipine towards zebrafish embryos: Abnormal ocular development, cardiac dysfunction, and malformed intersegmental vessels |
| title_short | Enantioselective toxicity of (S)-amlodipine towards zebrafish embryos: Abnormal ocular development, cardiac dysfunction, and malformed intersegmental vessels |
| title_sort | enantioselective toxicity of s amlodipine towards zebrafish embryos abnormal ocular development cardiac dysfunction and malformed intersegmental vessels |
| topic | Enantiomers Amlodipine Enantioselective toxicity Abnormal ocular development Heart dysfunction |
| url | http://www.sciencedirect.com/science/article/pii/S0147651325006517 |
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