2026-04-13T07:10:52Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/2188132025-12-05T14:16:56Zcom_2072_1057col_2072_478816col_2072_478902col_2072_478917

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 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 Peix zebra Toxicologia Embriologia Zebra danio Toxicology Embryology <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> 2025-02-17T07:54:06Z 2025-02-17T07:54:06Z 2025-01-22 2025-02-17T07:54:06Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 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 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 Elsevier Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)