Study of acute lethality, teratogenesis, and metabolomic changes of N-(2’-hydroxyphenyl)-2-propylpentanamide (HO-AAVPA) on Artemia franciscana
Abstract The brine shrimp lethality test (Artemia spp.) is a classical model for assessing the toxicity of bioactive compounds. This study evaluated the toxicity and metabolomic changes induced by N-(2’- hydroxyphenyl)-2-propylpentanamide (HO-AAVPA), a derivative of valproic acid (VPA), in Artemia f...
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Nature Portfolio
2025-05-01
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| Online Access: | https://doi.org/10.1038/s41598-025-03325-9 |
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| author | Cynthia Fernández-Pomares Alan Rubén Estrada-Pérez Humberto L. Mendoza-Figueroa Juan Benjamín García-Vázquez Martha C. Rosales-Hernández José Correa-Basurto |
| author_facet | Cynthia Fernández-Pomares Alan Rubén Estrada-Pérez Humberto L. Mendoza-Figueroa Juan Benjamín García-Vázquez Martha C. Rosales-Hernández José Correa-Basurto |
| author_sort | Cynthia Fernández-Pomares |
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| description | Abstract The brine shrimp lethality test (Artemia spp.) is a classical model for assessing the toxicity of bioactive compounds. This study evaluated the toxicity and metabolomic changes induced by N-(2’- hydroxyphenyl)-2-propylpentanamide (HO-AAVPA), a derivative of valproic acid (VPA), in Artemia franciscana larvae using untargeted metabolomics through liquid chromatography–mass spectrometry (LC-MS/MS). The lethal concentration 50 (LC50) was determined by acute toxicity tests at 24 and 48 h, and teratogenic effects were assessed by measuring the larvae body length. Larval metabolomic changes were examined following 24- and 48-hour exposures to sublethal concentrations of HO-AAVPA (LC1 = 0.04 mM, LC10 = 0.2 mM) and VPA (LC1 = 1.79 mM, LC10 = 8.95 mM). After 48 h, HO-AAVPA had an LC50 of 0.32 mM, while VPA had 18.7 mM. VPA induced teratogenic effects at 9.6 mM; in contrast, HO-AAVPA only significantly affected the body length at 0.56 mM. Metabolomic analysis revealed that sublethal concentrations of HO-AAVPA affected the sphingolipid and glycerophospholipid metabolism, while VPA impacted alanine, aspartate, and glutamate metabolism. These findings suggest HO-AAVPA has high toxicity, but lower teratogenicity compared to VPA. In conclusion, the present study indicates that alterations in lipid and amino acid metabolism could be critical points in the mode of action of these compounds in A. franciscana. |
| format | Article |
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| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-d70b4765fbfd44a988b7bce3addcfab02025-08-20T03:16:50ZengNature PortfolioScientific Reports2045-23222025-05-0115111410.1038/s41598-025-03325-9Study of acute lethality, teratogenesis, and metabolomic changes of N-(2’-hydroxyphenyl)-2-propylpentanamide (HO-AAVPA) on Artemia franciscanaCynthia Fernández-Pomares0Alan Rubén Estrada-Pérez1Humberto L. Mendoza-Figueroa2Juan Benjamín García-Vázquez3Martha C. Rosales-Hernández4José Correa-Basurto5Laboratorio de Diseño y Desarrollo de Nuevos Fármacos e Innovación Biotecnológica, Escuela Superior de Medicina, Instituto Politécnico NacionalLaboratorio de Diseño y Desarrollo de Nuevos Fármacos e Innovación Biotecnológica, Escuela Superior de Medicina, Instituto Politécnico NacionalLaboratorio de Diseño y Desarrollo de Nuevos Fármacos e Innovación Biotecnológica, Escuela Superior de Medicina, Instituto Politécnico NacionalLaboratorio de Diseño y Desarrollo de Nuevos Fármacos e Innovación Biotecnológica, Escuela Superior de Medicina, Instituto Politécnico NacionalLaboratorio de Biofísica y Biocatálisis, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico NacionalLaboratorio de Diseño y Desarrollo de Nuevos Fármacos e Innovación Biotecnológica, Escuela Superior de Medicina, Instituto Politécnico NacionalAbstract The brine shrimp lethality test (Artemia spp.) is a classical model for assessing the toxicity of bioactive compounds. This study evaluated the toxicity and metabolomic changes induced by N-(2’- hydroxyphenyl)-2-propylpentanamide (HO-AAVPA), a derivative of valproic acid (VPA), in Artemia franciscana larvae using untargeted metabolomics through liquid chromatography–mass spectrometry (LC-MS/MS). The lethal concentration 50 (LC50) was determined by acute toxicity tests at 24 and 48 h, and teratogenic effects were assessed by measuring the larvae body length. Larval metabolomic changes were examined following 24- and 48-hour exposures to sublethal concentrations of HO-AAVPA (LC1 = 0.04 mM, LC10 = 0.2 mM) and VPA (LC1 = 1.79 mM, LC10 = 8.95 mM). After 48 h, HO-AAVPA had an LC50 of 0.32 mM, while VPA had 18.7 mM. VPA induced teratogenic effects at 9.6 mM; in contrast, HO-AAVPA only significantly affected the body length at 0.56 mM. Metabolomic analysis revealed that sublethal concentrations of HO-AAVPA affected the sphingolipid and glycerophospholipid metabolism, while VPA impacted alanine, aspartate, and glutamate metabolism. These findings suggest HO-AAVPA has high toxicity, but lower teratogenicity compared to VPA. In conclusion, the present study indicates that alterations in lipid and amino acid metabolism could be critical points in the mode of action of these compounds in A. franciscana.https://doi.org/10.1038/s41598-025-03325-9Acute toxicity textLC-MS/MSValproic acidHistone deacetylase inhibitorsUntargeted metabolomics. |
| spellingShingle | Cynthia Fernández-Pomares Alan Rubén Estrada-Pérez Humberto L. Mendoza-Figueroa Juan Benjamín García-Vázquez Martha C. Rosales-Hernández José Correa-Basurto Study of acute lethality, teratogenesis, and metabolomic changes of N-(2’-hydroxyphenyl)-2-propylpentanamide (HO-AAVPA) on Artemia franciscana Scientific Reports Acute toxicity text LC-MS/MS Valproic acid Histone deacetylase inhibitors Untargeted metabolomics. |
| title | Study of acute lethality, teratogenesis, and metabolomic changes of N-(2’-hydroxyphenyl)-2-propylpentanamide (HO-AAVPA) on Artemia franciscana |
| title_full | Study of acute lethality, teratogenesis, and metabolomic changes of N-(2’-hydroxyphenyl)-2-propylpentanamide (HO-AAVPA) on Artemia franciscana |
| title_fullStr | Study of acute lethality, teratogenesis, and metabolomic changes of N-(2’-hydroxyphenyl)-2-propylpentanamide (HO-AAVPA) on Artemia franciscana |
| title_full_unstemmed | Study of acute lethality, teratogenesis, and metabolomic changes of N-(2’-hydroxyphenyl)-2-propylpentanamide (HO-AAVPA) on Artemia franciscana |
| title_short | Study of acute lethality, teratogenesis, and metabolomic changes of N-(2’-hydroxyphenyl)-2-propylpentanamide (HO-AAVPA) on Artemia franciscana |
| title_sort | study of acute lethality teratogenesis and metabolomic changes of n 2 hydroxyphenyl 2 propylpentanamide ho aavpa on artemia franciscana |
| topic | Acute toxicity text LC-MS/MS Valproic acid Histone deacetylase inhibitors Untargeted metabolomics. |
| url | https://doi.org/10.1038/s41598-025-03325-9 |
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