Neuroprotective effects of N-acetylcysteine-amide (AD4) in a Survival Mouse Model of Paraoxon Intoxication: Targeting Oxidative Stress, Neuroinflammation and Memory Impairments.
Neurotoxicity induced by organophosphorus (OP) compounds such as paraoxon (POX)</p><p>leads to severe brain damage and cognitive impairments. Although current treatments</p><p>alleviate acute cholinergic symptoms, they fail to address secondary neurotoxicity. This</p>&l...
| Autores: | , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:2445/224905 |
| Acceso en línea: | https://hdl.handle.net/2445/224905 |
| Access Level: | acceso abierto |
| Palabra clave: | Estrès oxidatiu Neuroimmunologia Inflamació Oxidative stress Neuroimmunology Inflammation |
| Sumario: | Neurotoxicity induced by organophosphorus (OP) compounds such as paraoxon (POX)</p><p>leads to severe brain damage and cognitive impairments. Although current treatments</p><p>alleviate acute cholinergic symptoms, they fail to address secondary neurotoxicity. This</p><p>study investigated the therapeutic potential of N-acetylcysteine-amide (AD4), a blood–</p><p>brain-barrier permeable antioxidant, in a survival mouse model of acute POX intoxication.</p><p>Male Swiss CD-1 mice received POX (4 mg/kg) followed by standard emergency therapy</p><p>(atropine, pralidoxime and diazepam). AD4 (150 mg/kg) was administered 2 and 6 h</p><p>post-exposure. AD4 treatment effectively prevented oxidative stress by reducing lipid</p><p>peroxidation and restoring the expression in hippocampus (HP) and/or prefrontal cortex</p><p>(PFC) of key antioxidant enzymes such as glutathione peroxidase-1 (GPx-1) and catalase</p><p>(CAT) suppressed by POX acute exposure. Moreover, AD4 attenuated neuroinflammation</p><p>in specific hippocampal subregions, as evidenced by reduced Glial Fibrillary Acidic Protein</p><p>(GFAP) and Ionized Calcium Binding Adaptor Molecule 1 (Iba-1) immunoreactivity. Im-</p><p>portantly, AD4 also rescued recognition memory deficits, as assessed by the Novel Object</p><p>Recognition Test (NORT). In summary, these findings demonstrate that AD4 mitigates</p><p>oxidative stress, neuroinflammation, and cognitive dysfunction following acute POX in-</p><p>toxication, supporting its potential as an adjuvant therapy for mitigating the secondary</p><p>neurotoxicity derived from organophosphorus poisoning. |
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