Urquizu, EdurneCuiller, MarinePapadopoulou, GeorgiaPubill Sánchez, DavidRaldúa, DemetrioCamarasa García, JordiEscubedo Rafa, ElenaLópez-Arnau, Raúl2025-12-152025-12-152025-12-062076-3921https://hdl.handle.net/2445/224905Neurotoxicity 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.19 p.application/pdfengcc-by (c) Edurne Urquizu et al., 2025http://creativecommons.org/licenses/by/4.0/Estrès oxidatiuNeuroimmunologiaInflamacióOxidative stressNeuroimmunologyInflammationinfo:eu-repo/semantics/article7629352025-12-15info:eu-repo/semantics/openAccess