N-Acetylcysteine-Amide Protects Against Acute Acrylamide Neurotoxicity in Adult Zebrafish
Acrylamide (ACR) is a potent neurotoxicant that disrupts cellular redox homeostasis by depleting reduced glutathione (GSH) and inducing oxidative stress. Despite its well-characterized mechanism, no effective treatments for ACR-induced neurotoxicity currently exist. This study evaluates the therapeu...
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MDPI AG
2025-04-01
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| Series: | Toxics |
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| Online Access: | https://www.mdpi.com/2305-6304/13/5/362 |
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| author | Niki Tagkalidou Júlia Goyenechea-Cunillera Irene Romero-Alfano Maria Olivella Martí Juliette Bedrossiantz Eva Prats Cristian Gomez-Canela Demetrio Raldúa |
| author_facet | Niki Tagkalidou Júlia Goyenechea-Cunillera Irene Romero-Alfano Maria Olivella Martí Juliette Bedrossiantz Eva Prats Cristian Gomez-Canela Demetrio Raldúa |
| author_sort | Niki Tagkalidou |
| collection | DOAJ |
| description | Acrylamide (ACR) is a potent neurotoxicant that disrupts cellular redox homeostasis by depleting reduced glutathione (GSH) and inducing oxidative stress. Despite its well-characterized mechanism, no effective treatments for ACR-induced neurotoxicity currently exist. This study evaluates the therapeutic efficacy of N-acetylcysteine-amide (AD4), a blood–brain barrier (BBB)-permeable derivative of N-acetylcysteine, in a novel severe acute ACR neurotoxicity model in adult zebrafish. Adult zebrafish received a single intraperitoneal (i.p.) injection of ACR (800 μg/g), followed by AD4 (400 μg/g i.p.) or PBS 24 h later. ACR exposure reduced brain GSH levels by 51% reduction at 48 h, an effect fully reversed by AD4 treatment. Behavioral analyses showed that AD4 rescued ACR-induced deficits in short-term habituation of the acoustic startle response (ASR). Surprisingly, ACR exposure did not alter the neurochemical profile of key neurotransmitters or the expression of genes related to redox homeostasis, synaptic vesicle recycling, regeneration, or myelination. These results demonstrate AD4’s neuroprotective effects against acute ACR-induced brain toxicity, highlighting its therapeutic potential and validating adult zebrafish as a translational model for studying neurotoxic mechanisms and neuroprotective interventions. |
| format | Article |
| id | doaj-art-3270606f44d44c3ebaf980e4b0ad609d |
| institution | DOAJ |
| issn | 2305-6304 |
| language | English |
| publishDate | 2025-04-01 |
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| series | Toxics |
| spelling | doaj-art-3270606f44d44c3ebaf980e4b0ad609d2025-08-20T03:12:04ZengMDPI AGToxics2305-63042025-04-0113536210.3390/toxics13050362N-Acetylcysteine-Amide Protects Against Acute Acrylamide Neurotoxicity in Adult ZebrafishNiki Tagkalidou0Júlia Goyenechea-Cunillera1Irene Romero-Alfano2Maria Olivella Martí3Juliette Bedrossiantz4Eva Prats5Cristian Gomez-Canela6Demetrio Raldúa7Institute for Environmental Assessment and Water Research (IDAEA-CSIC), Jordi Girona, 18, 08034 Barcelona, SpainDepartment of Analytical and Applied Chemistry, School of Engineering, Institut Químic de Sarrià-Universitat Ramon Llull, Via Augusta 390, 08017 Barcelona, SpainDepartment of Analytical and Applied Chemistry, School of Engineering, Institut Químic de Sarrià-Universitat Ramon Llull, Via Augusta 390, 08017 Barcelona, SpainDepartment of Analytical and Applied Chemistry, School of Engineering, Institut Químic de Sarrià-Universitat Ramon Llull, Via Augusta 390, 08017 Barcelona, SpainInstitute for Environmental Assessment and Water Research (IDAEA-CSIC), Jordi Girona, 18, 08034 Barcelona, SpainResearch and Development Center (CID-CSIC), Jordi Girona, 18, 08034 Barcelona, SpainDepartment of Analytical and Applied Chemistry, School of Engineering, Institut Químic de Sarrià-Universitat Ramon Llull, Via Augusta 390, 08017 Barcelona, SpainInstitute for Environmental Assessment and Water Research (IDAEA-CSIC), Jordi Girona, 18, 08034 Barcelona, SpainAcrylamide (ACR) is a potent neurotoxicant that disrupts cellular redox homeostasis by depleting reduced glutathione (GSH) and inducing oxidative stress. Despite its well-characterized mechanism, no effective treatments for ACR-induced neurotoxicity currently exist. This study evaluates the therapeutic efficacy of N-acetylcysteine-amide (AD4), a blood–brain barrier (BBB)-permeable derivative of N-acetylcysteine, in a novel severe acute ACR neurotoxicity model in adult zebrafish. Adult zebrafish received a single intraperitoneal (i.p.) injection of ACR (800 μg/g), followed by AD4 (400 μg/g i.p.) or PBS 24 h later. ACR exposure reduced brain GSH levels by 51% reduction at 48 h, an effect fully reversed by AD4 treatment. Behavioral analyses showed that AD4 rescued ACR-induced deficits in short-term habituation of the acoustic startle response (ASR). Surprisingly, ACR exposure did not alter the neurochemical profile of key neurotransmitters or the expression of genes related to redox homeostasis, synaptic vesicle recycling, regeneration, or myelination. These results demonstrate AD4’s neuroprotective effects against acute ACR-induced brain toxicity, highlighting its therapeutic potential and validating adult zebrafish as a translational model for studying neurotoxic mechanisms and neuroprotective interventions.https://www.mdpi.com/2305-6304/13/5/362acrylamideneurotoxicityzebrafish modelglutathioneacoustic startle responsehabituation |
| spellingShingle | Niki Tagkalidou Júlia Goyenechea-Cunillera Irene Romero-Alfano Maria Olivella Martí Juliette Bedrossiantz Eva Prats Cristian Gomez-Canela Demetrio Raldúa N-Acetylcysteine-Amide Protects Against Acute Acrylamide Neurotoxicity in Adult Zebrafish Toxics acrylamide neurotoxicity zebrafish model glutathione acoustic startle response habituation |
| title | N-Acetylcysteine-Amide Protects Against Acute Acrylamide Neurotoxicity in Adult Zebrafish |
| title_full | N-Acetylcysteine-Amide Protects Against Acute Acrylamide Neurotoxicity in Adult Zebrafish |
| title_fullStr | N-Acetylcysteine-Amide Protects Against Acute Acrylamide Neurotoxicity in Adult Zebrafish |
| title_full_unstemmed | N-Acetylcysteine-Amide Protects Against Acute Acrylamide Neurotoxicity in Adult Zebrafish |
| title_short | N-Acetylcysteine-Amide Protects Against Acute Acrylamide Neurotoxicity in Adult Zebrafish |
| title_sort | n acetylcysteine amide protects against acute acrylamide neurotoxicity in adult zebrafish |
| topic | acrylamide neurotoxicity zebrafish model glutathione acoustic startle response habituation |
| url | https://www.mdpi.com/2305-6304/13/5/362 |
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