{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T13:42:10Z","timestamp":1792330930817,"version":"4.4.0"},"reference-count":52,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T00:00:00Z","timestamp":1792281600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T00:00:00Z","timestamp":1792281600000},"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":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Vincristine (VIN) is a widely used chemotherapeutic agent whose therapeutic application is substantially constrained by concentration\u2010dependent toxicities, including nephrotoxicity. This study aimed to characterize the renoprotective capacity of hesperidin (HES) in a VIN\u2010induced nephrotoxicity model and to delineate the mechanisms underlying its protective action. Twenty\u2010eight female Wistar albino rats were divided into four groups: control, HES (200\u2009mg\/kg), VIN (0.17\u2009mg\/kg), and VIN (0.17\u2009mg\/kg) + HES (200\u2009mg\/kg), with all treatments administered for 7 consecutive days. Renal function markers, oxidative stress parameters, apoptosis\u2010 and autophagy\u2010related gene expression, phosphoinositide 3\u2010kinase (PI3K)\/protein kinase B (Akt)\/mammalian target of rapamycin (mTOR) signaling components, and histopathological alterations were evaluated. VIN administration significantly increased serum urea and creatinine levels, lipid peroxidation, and oxidative DNA damage, while reducing antioxidant defenses (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). VIN also induced marked apoptosis, evidenced by increased tumor protein p53 (p53), Bcl\u20102\u2010associated X protein (Bax), Caspase\u20103, and C\/EBP homologous protein (CHOP) expression and decreased B\u2010cell lymphoma 2 (Bcl\u20102) levels, together with enhanced autophagy and suppression of PI3K\/Akt\/mTOR signaling (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). These molecular changes were accompanied by severe renal histopathological damage (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). HES supplementation significantly attenuated these effects by restoring antioxidant capacity, reducing inflammatory cytokines, suppressing apoptosis, modulating autophagy\u2010related gene expression, and partially restoring PI3K\/Akt\/mTOR signaling (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). Histopathological findings further confirmed the protective effect of HES against VIN\u2010induced renal injury (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). In conclusion, HES exerts renoprotective effects against VIN\u2010induced nephrotoxicity by modulating interconnected oxidative stress, inflammation, apoptosis, autophagy, and PI3K\/Akt\/mTOR signaling pathways, suggesting its potential as a multi\u2010target agent for preventing chemotherapy\u2010associated renal injury in this experimental model.\n                  <\/jats:p>","DOI":"10.1002\/jbt.71136","type":"journal-article","created":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T13:00:46Z","timestamp":1792328446000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hesperidin Attenuates Vincristine\u2010Induced Nephrotoxicity via Nrf2\/HO\u20101 and PI3K\/Akt\/mTOR Signaling"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5367-0743","authenticated-orcid":false,"given":"Aydin","family":"Genc","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Faculty of Veterinary Medicine Bingol University Bingol T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6721-9387","authenticated-orcid":false,"given":"Bayram","family":"Akoglan","sequence":"additional","affiliation":[{"name":"Animal Nutrition and Nutritional Disease Department, Faculty of Veterinary Medicine Bingol University Bingol T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7625-1883","authenticated-orcid":false,"given":"Emre","family":"Sahin","sequence":"additional","affiliation":[{"name":"Animal Nutrition and Nutritional Disease Department, Faculty of Veterinary Medicine Bingol University Bingol T\u00fcrkiye"},{"name":"Department of Veterinary Biostatistics, Health Sciences Institute Ankara University Ankara T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3456-398X","authenticated-orcid":false,"given":"Eren","family":"Cankaya","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Veterinary Medicine Firat University Elazig Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,18]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.22037\/jpn.v12i1.45705"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.4067\/S0717-95022019000100273"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.4103\/njecp.njecp_35_21"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-026-05691-y"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22116109"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-57300-x"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17111826"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2022.110073"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sjbs.2022.01.052"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11071261"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2023.108369"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2018.06.012"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-40454-5"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.70829"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(66)90167-9"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/34.3.497"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0076-6879(84)05016-3"},{"key":"e_1_2_12_19_1","first-page":"248","article-title":"\u201cDetermination of Enzyme Activity in Lipid Peroxidation and Glutathione Pathways","volume":"15","author":"Matkovics B.","year":"1988","journal-title":"Laboratoriumi Diagnosztika"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(68)90092-4"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)52451-6"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.5c02662"},{"key":"e_1_2_12_24_1","volume-title":"Manual of Histologic Staining Methods of the Armed Forces Institute of Pathology","author":"Luna L. 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