{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:52:58Z","timestamp":1792788778216,"version":"4.5.0"},"reference-count":58,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006701","name":"Umm Al-Qura University","doi-asserted-by":"publisher","award":["26UQU4310453GSSR01"],"award-info":[{"award-number":["26UQU4310453GSSR01"]}],"id":[{"id":"10.13039\/501100006701","id-type":"DOI","asserted-by":"publisher"}]},{"award":["26UQU4310453GSSR01"],"award-info":[{"award-number":["26UQU4310453GSSR01"]}],"id":[{"id":"https:\/\/ror.org\/01xjqrm90","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Paracetamol overdose is a major cause of drug-induced acute kidney injury (AKI), driven by oxidative stress, inflammation, mitochondrial dysfunction, and tubular apoptosis. This study evaluated the nephroprotective efficacy of pH-responsive carboxymethyl cellulose-encapsulated hesperidin-stabilized selenium nanoparticles (CMC@HES-SeNPs) against paracetamol-induced AKI in rats. HES-SeNPs were synthesized using hesperidin as a reducing\/stabilizing agent and further coated with CMC. The nanoparticles were characterized by DLS, zeta potential, TEM, and in vitro release kinetics at pH 7.4 and 5.5. 42 Male rats were allocated into groups of control, paracetamol (PAR), paracetamol treated with sodium selenite (PAR&amp;Se), paracetamol treated with hesperidin (PAR&amp;HES), paracetamol treated with hesperidin-loaded selenium nanoparticles (PAR&amp;HES-SeNPs), and paracetamol treated with carboxy methyl cellulose-coated hesperidin-loaded selenium nanoparticles (PAR&amp;CMC@HES-SeNPs). Paracetamol markedly impaired renal function, increasing creatinine, urea, NGAL, KIM-1, and cystatin-C, and induced oxidative\/nitrosative stress, Keap-1 upregulation, Nrf2 suppression, NF-\u03baB-mediated inflammation, cytochrome-C release, Bax\/Bcl-2 imbalance, caspase-3 activation, and severe renal histopathological injury. CMC@HES-SeNPs displayed sustained, pH-enhanced hesperidin release and produced the strongest renoprotective response, restoring renal biomarkers, associated with restoration of Keap-1\/Nrf2-related antioxidant markers, reduction in TNF-\u03b1, IL-6, NF-\u03baB, and caspase-3, increased IL-10, and preservation of renal architecture. Collectively, these results indicate that CMC@HES-SeNPs represent a promising multifunctional nanoplatform for mitigating paracetamol-induced AKI in association with coordinated modulation of redox, inflammatory, and mitochondrial apoptotic markers, and highlight CMC encapsulation as a rational strategy to enhance selenium\u2013flavonoid delivery and efficacy for future drug-induced AKI management and translation.<\/jats:p>","DOI":"10.3390\/ijms27157049","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T09:46:38Z","timestamp":1786009598000},"page":"7049","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["pH-Responsive Carboxymethyl Cellulose-Encapsulating Hesperidin\u2013Selenium Nanoparticles Attenuate Paracetamol-Induced Acute Kidney Injury via Keap-1\/Nrf2, NF-\u03baB, and Mitochondrial Apoptosis Modulation"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1976-9480","authenticated-orcid":false,"given":"Mohamed H. A.","family":"Gadelmawla","sequence":"first","affiliation":[{"name":"Department of Life Sciences, Faculty of Biotechnology, Sinai University, Kantara Branch, Ismailia 41636, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1140-8338","authenticated-orcid":false,"given":"Khaled M.","family":"Alam-Eldein","sequence":"additional","affiliation":[{"name":"School of Biotechnology, Badr University InCairo (BUC), Badr City 11829, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afnan","family":"Saleh","sequence":"additional","affiliation":[{"name":"School of Biotechnology, Badr University InCairo (BUC), Badr City 11829, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sama","family":"Adel","sequence":"additional","affiliation":[{"name":"School of Biotechnology, Badr University InCairo (BUC), Badr City 11829, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haneen","family":"Ali","sequence":"additional","affiliation":[{"name":"School of Biotechnology, Badr University InCairo (BUC), Badr City 11829, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaza","family":"Ayman","sequence":"additional","affiliation":[{"name":"School of Biotechnology, Badr University InCairo (BUC), Badr City 11829, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esraa","family":"Tarek","sequence":"additional","affiliation":[{"name":"School of Biotechnology, Badr University InCairo (BUC), Badr City 11829, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nievin Ahmed","family":"Mahran","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Biotechnology, Sinai University, Kantara Branch, Ismailia 41636, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2118-0499","authenticated-orcid":false,"given":"Ahmed M.","family":"Ashour","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, Umm Al-Qura University, P.O. Box 13578, Makkah 21955, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0636-7685","authenticated-orcid":false,"given":"Nasser M.","family":"Alorfi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, Umm Al-Qura University, P.O. Box 13578, Makkah 21955, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6966-0128","authenticated-orcid":false,"given":"Fahad S.","family":"Alshehri","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, Umm Al-Qura University, P.O. Box 13578, Makkah 21955, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4816-4421","authenticated-orcid":false,"given":"Wessam N.","family":"El-Sayed","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Science, Suez University, Suez 43221, Egypt"},{"name":"Chemistry Department, College of Science, University of Jeddah, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2568-6059","authenticated-orcid":false,"given":"Ahmed Hassan Ibrahim","family":"Faraag","sequence":"additional","affiliation":[{"name":"School of Biotechnology, Badr University InCairo (BUC), Badr City 11829, Egypt"},{"name":"Botany and Microbiology Department, Faculty of Science, Capital University (Formly Helwan University), Helwan 11795, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Khames","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Sohag University, Sohag 82511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salma M.","family":"Selim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Sinai University, Kantara, Ismailia 41636, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1080\/17425255.2023.2259787","article-title":"Advances in the Understanding of Acetaminophen Toxicity Mechanisms: A Clinical Toxicology Perspective","volume":"19","author":"Chiew","year":"2023","journal-title":"Expert Opin. 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