{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T06:46:12Z","timestamp":1789541172249,"version":"build-2803163510"},"reference-count":85,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Chlorfenapyr (CFP) is a widely used pesticide associated with significant toxicological effects, including reproductive toxicity. Rosmarinic acid (RA) possesses potent antioxidant and anti\u2010inflammatory properties; however, its therapeutic application may be limited by poor physicochemical characteristics. This study investigated the molecular mechanisms underlying CFP\u2010induced testicular toxicity and evaluated whether nano\u2010encapsulation of RA within Chitosan nanoparticles (RA\u2010CHNPs) improves its protective efficacy against CFP\u2010induced reproductive damage. A total of 60 adult male Wistar rats were allocated into six groups (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200910\/group): control, RA, RA\u2010CHNPs, CFP, CFP\u2009+\u2009RA, and CFP\u2009+\u2009RA\u2010CHNPs. Animals received oral CFP (180\u2009mg\/kg\/day) and\/or RA (75\u2009mg\/kg\/day, crude or nano\u2010encapsulated) for 30 consecutive days. CFP exposure significantly reduced testicular weight, sperm count, sperm motility, luteinizing hormone, follicle\u2010stimulating hormone, and testosterone levels. These alterations were accompanied by oxidative stress, increased pro\u2010inflammatory cytokine production, apoptosis, and activation of NF\u2010\u03baB\/NLRP3 signaling. Immunohistochemical analysis revealed marked NF\u2010\u03baB expression in spermatogenic and Leydig cells, together with strong NLRP3 expression within seminiferous tubules. Co\u2010administration of RA\u2010CHNPs was associated with a marked attenuation of these adverse effects, denoting greater protective efficacy than crude RA. RA\u2010CHNPs reduced NF\u2010\u03baB and NLRP3 expression, which was accompanied by improved testicular architecture, restored spermatogenic activity, and normalized reproductive hormone levels. These protective effects were associated with activation of the NRF2\/HO\u20101 antioxidant pathway, suppression of inflammatory responses, and regulation of apoptosis\u2010related genes. Overall, RA\u2010loaded Chitosan nanoparticles provided superior protection against CFP\u2010induced testicular toxicity compared with crude RA, highlighting the potential of nanoformulation strategies to enhance RA's biological efficacy.\n                  <\/jats:p>","DOI":"10.1002\/jbt.71037","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T13:50:27Z","timestamp":1784641827000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Nano\u2010Rosmarinic Acid Protects Against Chlorfenapyr\u2010Induced Testicular Toxicity Through Modulation of NRF2\/HO\u20101 and NF\u2010\u03baB\/NLRP3 Signaling Pathways"],"prefix":"10.1002","volume":"40","author":[{"given":"Ahmad Najem","family":"Alshammari","sequence":"first","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"},{"name":"Editome: Precision Gene Editing Unit, King Fahd Medical Research Center King Abdulaziz University Jeddah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huda A. Al","family":"Doghaither","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Science King Abdulaziz University Jeddah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed M. S.","family":"Hegazy","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Faculty of Medicine Northern Border University Arar 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\/0000-0002-6104-562X","authenticated-orcid":false,"given":"Asmaa Fady","family":"Sharif","sequence":"additional","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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7836-9639","authenticated-orcid":false,"given":"Zahraa Khalifa","family":"Sobh","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine Alexandria University Alexandria Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-023-04758-1"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2024.1464003"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s41935-025-00494-6"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/and.13978"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.21608\/asejaiqjsae.2021.177465"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.21608\/asejaiqjsae.2021.201175"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12011-021-02704-3"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2022.153208"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27175722"},{"issue":"1","key":"e_1_2_10_11_1","first-page":"38","article-title":"Protective Effect of Rosmarinic Acid Against Cisplatin\u2010Induced Testicular Damage in Mice via Modulation of Inflammation, Oxidative Stress, and Apoptosis and Restoration of Nrf2\/HO\u20101","volume":"11","author":"Norman B.","year":"2025","journal-title":"Journal of Basic and Applied Research in Biomedicine"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0314093"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2022.121281"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.36516\/jocass.1619585"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-023-02788-9"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.70179"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/fsn3.70452"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.114687"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12272-022-01378-2"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.21937"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/stresses4030032"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cryobiol.2025.105548"},{"issue":"1","key":"e_1_2_10_23_1","first-page":"143","article-title":"Enhanced Drug Delivery With Nanocarriers: A Comprehensive Review of Recent Advances in Breast Cancer Detection and Treatment. 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