{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T03:02:36Z","timestamp":1792638156776,"version":"4.5.0"},"reference-count":73,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Doxorubicin (DOX)-induced nephrotoxicity remains a major limitation to its clinical use, yet the underlying epigenetic mechanisms are incompletely understood. This study investigated the role of epigenetic dysregulation and MyD88\/STAT3 signaling in DOX-induced renal injury and evaluated the renoprotective efficacy of rutin-loaded nanostructured lipid carriers (RUT-NLCs) compared with free rutin (RUT). Thirty-six rats were allocated to six experimental groups, and renal function, oxidative stress, inflammation, DNA damage, epigenetic modifications, MyD88\/STAT3 signaling, histopathology, and ultrastructural changes were assessed. DOX administration induced severe renal dysfunction, oxidative stress, DNA damage, tubular injury, global DNA hypermethylation, aberrant histone methylation, Klotho promoter hypermethylation, and activation of the MyD88\/STAT3 inflammatory pathway. Treatment with RUT-NLCs significantly attenuated these alterations by restoring antioxidant defenses, normalizing epigenetic markers, reducing DNA damage, suppressing MyD88\/STAT3 signaling, and improving renal histopathological and ultrastructural architecture. Overall, RUT-NLCs provided greater nephroprotection than free rutin, suggesting that modulation of epigenetic alterations and MyD88\/STAT3 signaling represents a key mechanism underlying their therapeutic efficacy against DOX-induced nephrotoxicity.<\/jats:p>","DOI":"10.3390\/toxics14080713","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T14:45:06Z","timestamp":1786545906000},"page":"713","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Rutin-Loaded Nanostructured Lipid Carriers Attenuate Doxorubicin-Induced Nephrotoxicity and Modulate Epigenetic Regulation and MyD88\/STAT3 Signaling"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3014-9909","authenticated-orcid":false,"given":"Amina","family":"Farag","sequence":"first","affiliation":[{"name":"Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Benha University, Benha 13518, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walaa","family":"El Gazzar","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Physiology and Biochemistry, Faculty of Medicine, The Hashemite University, Zarqa 13133, Jordan"},{"name":"Department of Medical Biochemistry & Molecular Biology, Faculty of Medicine, Benha University, Benha 13518, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6425-9247","authenticated-orcid":false,"given":"Mahmoud","family":"Mostafa","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia 61519, Egypt"},{"name":"Department of Pharmaceutics, Faculty of Pharmacy, Minia National University, New Minia 61768, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Mohammed","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry & Molecular Biology, Faculty of Medicine, Benha University, Benha 13518, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0825-9776","authenticated-orcid":false,"given":"Azza","family":"El-Demerdash","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Agricultural Research Center (ARC), Animal Health Research Institute (AHRI), Zagazig Branch, Zagazig 44516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagah","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Benha University, Benha 13518, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranih","family":"Amer","sequence":"additional","affiliation":[{"name":"Department of Oral Surgery and Diagnostic Sciences, Applied Science Private University (ASU), Amman 11937, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8267-1718","authenticated-orcid":false,"given":"Heba","family":"Youssef","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Benha University, Benha 13518, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noha","family":"El-Shaer","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Benha University, Benha 13518, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4161-4263","authenticated-orcid":false,"given":"Ibrahim","family":"Mostafa","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Benha University, Benha 13518, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haidy","family":"Fakher","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Benha University, Benha 13518, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0648-0979","authenticated-orcid":false,"given":"Sahar","family":"Soliman","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, College of Osteopathic Medicine, Sam Houston State University, Conroe, TX 77304, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"111147","DOI":"10.1016\/j.cbi.2024.111147","article-title":"Phosphocreatine attenuates doxorubicin-induced nephrotoxicity through inhibition of apoptosis, and restore mitochondrial function via activation of Nrf2 and PGC-1\u03b1 pathways","volume":"400","author":"Qaed","year":"2024","journal-title":"Chem. 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