Combining the zebrafish embryo developmental toxicity assay (ZEDTA) with hemoglobin staining to accelerate the research of novel antimalarial drugs for pregnant women
<p>Background: Malaria during pregnancy implies a high risk for the mother and the developing child. However, the</p><p>therapeutic options for pregnant women have historically been very limited, especially during the first trimester</p><p>of pregnancy due to potential...
| Autores: | , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/218813 |
| Acceso en línea: | https://hdl.handle.net/2445/218813 |
| Access Level: | acceso abierto |
| Palabra clave: | Peix zebra Toxicologia Embriologia Zebra danio Toxicology Embryology |
| id |
ES_08fba8e4b0a496a76ed831783ca71799 |
|---|---|
| oai_identifier_str |
oai:diposit.ub.edu:2445/218813 |
| network_acronym_str |
ES |
| network_name_str |
España |
| repository_id_str |
|
| spelling |
Combining the zebrafish embryo developmental toxicity assay (ZEDTA) with hemoglobin staining to accelerate the research of novel antimalarial drugs for pregnant womenBorrallo-Lopez, LucíaGuzman, LauraRomero, Noelia GiselleSampietro, AnnaMallo Abreu, AnaGuardia Escoté, LaiaTeixidó Condomines, ElisabetFlick, BurkhardFernàndez Busquets, XavierMuñoz-Torrero López-Ibarra, DiegoBarenys Espadaler, MartaPeix zebraToxicologiaEmbriologiaZebra danioToxicologyEmbryology<p>Background: Malaria during pregnancy implies a high risk for the mother and the developing child. However, the</p><p>therapeutic options for pregnant women have historically been very limited, especially during the first trimester</p><p>of pregnancy due to potential adverse effects on embryo-fetal development. Recently, there has been great</p><p>controversy regarding these potential embryo-fetal adverse effects because the results of rodent studies were not</p><p>in accordance with the clinical data available, and finally the WHO has changed the recommendations for</p><p>pregnant women with uncomplicated <em>P. falciparum</em> malaria to treatment with artemether-lumefantrine during</p><p>the first trimester. The discrepancy between pre-clinical and clinical studies has been attributed to speciesdifferences</p><p>in the duration of the window of susceptibility of circulating primitive erythroblasts.</p><p>Methods: Here we provide a tool based on an alternative method to animal experimentation that accelerates the</p><p>research of novel drugs for pregnant women. We have adapted the zebrafish embryo developmental toxicity</p><p>assay to include hemoglobin staining in the embryos and two time-points of lethality and dysmorphogenesis</p><p>evaluation. These two time-points were selected to include one when the development is independent of and one</p><p>when the development is dependent of erythrocytes function. The method was used to test four marketed</p><p>antimalarial drugs and three new antimalarial drug candidates.</p><p>Results: Our combination of tests can correctly predict the teratogenic and non-teratogenic effects of several</p><p>antimalarial marketed drugs (artemisinin, quinine, chloroquine, and dihydroartemisinin + desbutyl-lumefantrine).</p><p>Furthermore, we have tested three new drug candidates (GS-GUAN, DONE3TCl, and YAT2150) with novel</p><p>mechanisms of action, and different from those of the marketed antimalarial drugs.</p><p>Conclusions: We propose a decision tree combining the results of the two time-points of evaluation together with</p><p>the information on significant erythrocyte depletion. The aim of this decision tree is to identify compounds with</p><p>no or lower hazard on teratogenicity or erythrocyte depletion at an early phase of the drug development process.</p>Elsevier2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/218813Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/https://doi.org/10.1016/j.ijpddr.2025.100582International Journal For Parasitology: Drugs And Drug Resistance, 2025, vol. 27https://doi.org/https://doi.org/10.1016/j.ijpddr.2025.100582cc-by-nc-nd (c) Borrallo-Lopez, L. et al., 2025http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2188132026-05-27T06:46:51Z |
| dc.title.none.fl_str_mv |
Combining the zebrafish embryo developmental toxicity assay (ZEDTA) with hemoglobin staining to accelerate the research of novel antimalarial drugs for pregnant women |
| title |
Combining the zebrafish embryo developmental toxicity assay (ZEDTA) with hemoglobin staining to accelerate the research of novel antimalarial drugs for pregnant women |
| spellingShingle |
Combining the zebrafish embryo developmental toxicity assay (ZEDTA) with hemoglobin staining to accelerate the research of novel antimalarial drugs for pregnant women Borrallo-Lopez, Lucía Peix zebra Toxicologia Embriologia Zebra danio Toxicology Embryology |
| title_short |
Combining the zebrafish embryo developmental toxicity assay (ZEDTA) with hemoglobin staining to accelerate the research of novel antimalarial drugs for pregnant women |
| title_full |
Combining the zebrafish embryo developmental toxicity assay (ZEDTA) with hemoglobin staining to accelerate the research of novel antimalarial drugs for pregnant women |
| title_fullStr |
Combining the zebrafish embryo developmental toxicity assay (ZEDTA) with hemoglobin staining to accelerate the research of novel antimalarial drugs for pregnant women |
| title_full_unstemmed |
Combining the zebrafish embryo developmental toxicity assay (ZEDTA) with hemoglobin staining to accelerate the research of novel antimalarial drugs for pregnant women |
| title_sort |
Combining the zebrafish embryo developmental toxicity assay (ZEDTA) with hemoglobin staining to accelerate the research of novel antimalarial drugs for pregnant women |
| dc.creator.none.fl_str_mv |
Borrallo-Lopez, Lucía Guzman, Laura Romero, Noelia Giselle Sampietro, Anna Mallo Abreu, Ana Guardia Escoté, Laia Teixidó Condomines, Elisabet Flick, Burkhard Fernàndez Busquets, Xavier Muñoz-Torrero López-Ibarra, Diego Barenys Espadaler, Marta |
| author |
Borrallo-Lopez, Lucía |
| author_facet |
Borrallo-Lopez, Lucía Guzman, Laura Romero, Noelia Giselle Sampietro, Anna Mallo Abreu, Ana Guardia Escoté, Laia Teixidó Condomines, Elisabet Flick, Burkhard Fernàndez Busquets, Xavier Muñoz-Torrero López-Ibarra, Diego Barenys Espadaler, Marta |
| author_role |
author |
| author2 |
Guzman, Laura Romero, Noelia Giselle Sampietro, Anna Mallo Abreu, Ana Guardia Escoté, Laia Teixidó Condomines, Elisabet Flick, Burkhard Fernàndez Busquets, Xavier Muñoz-Torrero López-Ibarra, Diego Barenys Espadaler, Marta |
| author2_role |
author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Peix zebra Toxicologia Embriologia Zebra danio Toxicology Embryology |
| topic |
Peix zebra Toxicologia Embriologia Zebra danio Toxicology Embryology |
| description |
<p>Background: Malaria during pregnancy implies a high risk for the mother and the developing child. However, the</p><p>therapeutic options for pregnant women have historically been very limited, especially during the first trimester</p><p>of pregnancy due to potential adverse effects on embryo-fetal development. Recently, there has been great</p><p>controversy regarding these potential embryo-fetal adverse effects because the results of rodent studies were not</p><p>in accordance with the clinical data available, and finally the WHO has changed the recommendations for</p><p>pregnant women with uncomplicated <em>P. falciparum</em> malaria to treatment with artemether-lumefantrine during</p><p>the first trimester. The discrepancy between pre-clinical and clinical studies has been attributed to speciesdifferences</p><p>in the duration of the window of susceptibility of circulating primitive erythroblasts.</p><p>Methods: Here we provide a tool based on an alternative method to animal experimentation that accelerates the</p><p>research of novel drugs for pregnant women. We have adapted the zebrafish embryo developmental toxicity</p><p>assay to include hemoglobin staining in the embryos and two time-points of lethality and dysmorphogenesis</p><p>evaluation. These two time-points were selected to include one when the development is independent of and one</p><p>when the development is dependent of erythrocytes function. The method was used to test four marketed</p><p>antimalarial drugs and three new antimalarial drug candidates.</p><p>Results: Our combination of tests can correctly predict the teratogenic and non-teratogenic effects of several</p><p>antimalarial marketed drugs (artemisinin, quinine, chloroquine, and dihydroartemisinin + desbutyl-lumefantrine).</p><p>Furthermore, we have tested three new drug candidates (GS-GUAN, DONE3TCl, and YAT2150) with novel</p><p>mechanisms of action, and different from those of the marketed antimalarial drugs.</p><p>Conclusions: We propose a decision tree combining the results of the two time-points of evaluation together with</p><p>the information on significant erythrocyte depletion. The aim of this decision tree is to identify compounds with</p><p>no or lower hazard on teratogenicity or erythrocyte depletion at an early phase of the drug development process.</p> |
| publishDate |
2025 |
| dc.date.none.fl_str_mv |
2025 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/2445/218813 |
| url |
https://hdl.handle.net/2445/218813 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Reproducció del document publicat a: https://doi.org/https://doi.org/10.1016/j.ijpddr.2025.100582 International Journal For Parasitology: Drugs And Drug Resistance, 2025, vol. 27 https://doi.org/https://doi.org/10.1016/j.ijpddr.2025.100582 |
| dc.rights.none.fl_str_mv |
cc-by-nc-nd (c) Borrallo-Lopez, L. et al., 2025 http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
cc-by-nc-nd (c) Borrallo-Lopez, L. et al., 2025 http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
Elsevier |
| publisher.none.fl_str_mv |
Elsevier |
| dc.source.none.fl_str_mv |
Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica) reponame:Dipòsit Digital de la UB instname:Universidad de Barcelona |
| instname_str |
Universidad de Barcelona |
| reponame_str |
Dipòsit Digital de la UB |
| collection |
Dipòsit Digital de la UB |
| repository.name.fl_str_mv |
|
| repository.mail.fl_str_mv |
|
| _version_ |
1869403079835648000 |
| score |
15,811543 |