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Their nephroprotective effects arise from antioxidant and anti\u2010inflammatory properties. This study investigated the potential protective effects of Saxagliptin and Cilostazol in rats with kidney damage induced by CYP. Five equal groups of 50 male Wistar rats were randomly categorised as Group I (Control group), Group II: CYP untreated nephrotoxicity\u2013induced group, Group III: Nephrotoxicity\u2010induced group treated with saxagliptin, Group IV: Nephrotoxicity\u2010induced group treated with cilostazol, and Group V: Nephrotoxicity\u2010induced group treated with saxagliptin and cilostazol. Renal tissues and blood samples were collected for biochemical analysis of urea, creatinine, and acute kidney injury biomarkers, including Kim\u20101 and NGAL. Additionally, oxidative stress and inflammatory biomarkers such as GSH, MDA, TNF\u2010\u03b1 and IL\u20101\u03b2 were assessed, along with gene expression of <jats:italic>Nrf\u20102\/HO\u20101<\/jats:italic> and <jats:italic>NF\u2010kB<\/jats:italic>. Immunohistochemical analysis of iNOS, and histopathological study were also conducted. Saxagliptin and cilostazol ameliorated the nephrotoxicity induced by CYP, as indicated by improvements in urea, creatinine, and acute kidney injury biomarkers Kim\u20101 and NGAL. Furthermore, there was a decrease in oxidative stress via the upregulation of <jats:italic>Nrf\u20102\/HO\u20101<\/jats:italic>, increased levels of GSH, downregulation of MDA and decreased inflammation via the downregulation of TNF\u2010\u03b1, IL\u20101\u03b2 and iNOS\/<jats:italic>NF\u2010kB<\/jats:italic>. The combination of saxagliptin and cilostazol demonstrated a significant improvement compared to using each agent individually. The combination of Saxagliptin\/Cilostazol is superior to monotherapy by either of each alone in preventing CYP\u2010induced nephrotoxicity.<\/jats:p>","DOI":"10.1002\/jbt.70196","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T02:10:18Z","timestamp":1741745418000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Protective Effects of Saxagliptin and Cilostazol in an Experimental Model of Cyclophosphamide\u2010Induced Nephrotoxicity in Rats: Targeting iNOS\/<i>NF<\/i>\u2010<i>kB<\/i> and <i>Nrf\u20102<\/i>\/<i>HO\u20101<\/i> Pathways"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6855-3758","authenticated-orcid":false,"given":"Monira A.","family":"Seleem","sequence":"first","affiliation":[{"name":"Department of Medical Pharmacology, Faculty of Medicine Tanta University Tanta Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6447-9522","authenticated-orcid":false,"given":"Ola M.","family":"Salem","sequence":"additional","affiliation":[{"name":"Department of Medical Pharmacology, Faculty of Medicine Tanta University Tanta Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8184-6459","authenticated-orcid":false,"given":"Eman","family":"Basha","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine Tanta University Tanta Egypt"},{"name":"Department of Basic Medical Sciences, Physiology, Faculty of Medicine Ibn Sina University for Medical Sciences Amman Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8230-6761","authenticated-orcid":false,"given":"Hoda A.","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of 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