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Acute exposure to CFP results in severe delayed neurotoxicity with potentially fatal outcomes. The mechanisms by which CFP exerts its neurotoxic effects are not fully understood, and no definitive treatment for acute CFP poisoning exists to date. Thus, the present study investigated the neurotoxic effects of CFP in male Wistar rats. Also, we evaluated the neuroprotective potential of curcumin (CUR) encapsulated in casein nanoparticles (CUR\u2010CasNPs) compared to free CUR. Sixty rats were randomly divided into six groups receiving control, CUR, CUR\u2010CasNPs, CFP, CFP\u2009+\u2009CUR, or CFP\u2009+\u2009CUR\u2010CasNPs orally for 30 consecutive days. CFP exposure significantly reduced hippocampal neurotransmitter levels, including dopamine, norepinephrine, and serotonin, decreased ATP content and pyruvate dehydrogenase activity, elevated oxidative and nitrosative stress markers such as malondialdehyde and nitric oxide, suppressed antioxidant defenses including glutathione, superoxide dismutase, catalase, and glutathione peroxidase, upregulated pro\u2010inflammatory cytokines (IL\u20101\u03b2, TNF\u2010\u03b1), activated NF\u2010\u03baB\/COX\u20102 signaling, and increased pro\u2010apoptotic gene expression (Bax, Caspase\u20103) while downregulating anti\u2010apoptotic Bcl\u20102 and Nrf2\/HO\u20101 signaling. Co\u2010administration of CUR\u2010CasNPs significantly mitigated these alterations, restoring neurotransmitter balance, enhancing antioxidant capacity, reducing inflammation and apoptosis, and preserving hippocampal microstructure more effectively than free CUR. Histological and ultrastructural analyses confirmed maintenance of neuronal architecture, reduced gliosis, and improved vascular integrity in CUR\u2010CasNPs\u2010treated rats. These findings demonstrate that nano\u2010formulation enhances CUR's stability, bioavailability, and overall neuroprotective efficacy, highlighting its potential as a therapeutic strategy to counteract CFP\u2010induced hippocampal neurotoxicity by simultaneously modulating oxidative stress, inflammatory pathways, apoptotic signaling, and energy metabolism<\/jats:p>","DOI":"10.1002\/jbt.70783","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T11:52:54Z","timestamp":1774612374000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Chlorfenapyr\u2010Induced Hippocampal Neurotoxicity Is Driven by Oxidative Stress\u2010Inflammation Crosstalk, Mitochondrial Dysfunction, and Neurotransmitter Dysregulation: Evidence From Curcumin\u2010Loaded Casein Nanoparticle Intervention"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6104-562X","authenticated-orcid":false,"given":"Asmaa Fady","family":"Sharif","sequence":"first","affiliation":[{"name":"Department of Clinical Medical Sciences, College of Medicine Dar Al\u2010Uloom University Riyadh Saudi Arabia"},{"name":"Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine Tanta University Tanta Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad Najem","family":"Alshammari","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Technology, College of Applied Medical Sciences Northern Border University Arar Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayat B.","family":"Al\u2010Ghafari","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Science King Abdulaziz University Jeddah Saudi Arabia"},{"name":"Experimental Biochemistry Unit, King Fahd Medical Research Center King Abdulaziz University Jeddah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huda A.","family":"Al Doghaither","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Science King Abdulaziz University Jeddah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7444-2499","authenticated-orcid":false,"given":"Ekramy M.","family":"Elmorsy","sequence":"additional","affiliation":[{"name":"Center for Health Research Northern Border University Arar Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7836-9639","authenticated-orcid":false,"given":"Zahraa Khalifa","family":"Sobh","sequence":"additional","affiliation":[{"name":"Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine Alexandria University Alexandria Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,27]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.7b02098"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/medicina58111630"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/00498254.2016.1236300"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/425179"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/1024907918782065"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/15563650.2024.2310748"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s41935-025-00494-6"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.4103\/0972-2327.112486"},{"key":"e_1_2_10_10_1","first-page":"497","article-title":"General Rules Discussion for Basic Treatment of Acute Chlorfenapyr Poisoning","volume":"43","author":"Cheng Y. 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