{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T06:14:11Z","timestamp":1765260851949,"version":"3.46.0"},"reference-count":80,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T00:00:00Z","timestamp":1764979200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NATO Science for Peace and Security Program","award":["SPS.MYP G5852"],"award-info":[{"award-number":["SPS.MYP G5852"]}]},{"DOI":"10.13039\/501100011033","name":"Agencia Estatal de Investigaci\u00f3n","doi-asserted-by":"publisher","award":["PID2023-148502OB-C21"],"award-info":[{"award-number":["PID2023-148502OB-C21"]}],"id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002809","name":"Generalitat de Catalunya","doi-asserted-by":"crossref","award":["2021SGR0090"],"award-info":[{"award-number":["2021SGR0090"]}],"id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Neurotoxicity induced by organophosphorus (OP) compounds such as paraoxon (POX) leads to severe brain damage and cognitive impairments. Although current treatments alleviate acute cholinergic symptoms, they fail to address secondary neurotoxicity. This study investigated the therapeutic potential of N-acetylcysteine-amide (AD4), a blood\u2013brain-barrier permeable antioxidant, in a survival mouse model of acute POX intoxication. Male Swiss CD-1 mice received POX (4 mg\/kg) followed by standard emergency therapy (atropine, pralidoxime and diazepam). AD4 (150 mg\/kg) was administered 2 and 6 h post-exposure. AD4 treatment effectively prevented oxidative stress by reducing lipid peroxidation and restoring the expression in hippocampus (HP) and\/or prefrontal cortex (PFC) of key antioxidant enzymes such as glutathione peroxidase-1 (GPx-1) and catalase (CAT) suppressed by POX acute exposure. Moreover, AD4 attenuated neuroinflammation in specific hippocampal subregions, as evidenced by reduced Glial Fibrillary Acidic Protein (GFAP) and Ionized Calcium Binding Adaptor Molecule 1 (Iba-1) immunoreactivity. Importantly, AD4 also rescued recognition memory deficits, as assessed by the Novel Object Recognition Test (NORT). In summary, these findings demonstrate that AD4 mitigates oxidative stress, neuroinflammation, and cognitive dysfunction following acute POX intoxication, supporting its potential as an adjuvant therapy for mitigating the secondary neurotoxicity derived from organophosphorus poisoning.<\/jats:p>","DOI":"10.3390\/antiox14121463","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T08:21:43Z","timestamp":1765182103000},"page":"1463","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neuroprotective Effects of N-Acetylcysteine-Amide (AD4) in a Survival Mouse Model of Paraoxon Intoxication: Targeting Oxidative Stress, Neuroinflammation and Memory Impairments"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7184-9461","authenticated-orcid":false,"given":"Edurne","family":"Urquizu","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutic Chemistry, Pharmacology Section and Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marine","family":"Cuiller","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutic Chemistry, Pharmacology Section and Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgia","family":"Papadopoulou","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutic Chemistry, Pharmacology Section and Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6627-4501","authenticated-orcid":false,"given":"David","family":"Pubill","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutic Chemistry, Pharmacology Section and Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5256-1641","authenticated-orcid":false,"given":"Demetrio","family":"Rald\u00faa","sequence":"additional","affiliation":[{"name":"Institute for Environmental Assessment and Water Research (IDAEA-CSIC), 08034 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jordi","family":"Camarasa","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutic Chemistry, Pharmacology Section and Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5078-366X","authenticated-orcid":false,"given":"Elena","family":"Escubedo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutic Chemistry, Pharmacology Section and Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8904-7398","authenticated-orcid":false,"given":"Raul","family":"L\u00f3pez-Arnau","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutic Chemistry, Pharmacology Section and Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Balali-Mood, M., and Abdollahi, M. 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