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This study was designed to evaluate empagliflozin ability to suppress the progression of 1,2\u2010dimethylhydrazine (DMH)\u2010induced colorectal cancer. An 8\u2010week regimen of 40\u2009mg\/kg\/twice a week of DMH to generate colorectal cancer. Three groups of eight male Wistar rats were created as follows: normal control, DMH group and DMH\u2009+\u2009empagliflozin (30\u2009mg\/kg; p.o.). The colonic levels of the antioxidant enzymes; superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were restored, empagliflozin adjusted the redox imbalance provoked by DMH. Immunohistochemical study proved the impact of empagliflozin in downregulating nuclear factor kappa B (NF\u2010\u03baB) that was elevated by DMH. Empagliflozin counteracted the DMH\u2010triggered inflammation by reducing vascular endothelial growth factor (VEGF), interlukin\u20106 (IL\u20106) and cyclooxygenase\u20102 (COX\u20102) levels. Empagliflozin hindered tumor cell proliferation which has supported by the decline in proliferating cell nuclear antigen (PCNA) mRNA expression. Empagliflozin halted the DMH\u2010activated oncogenic phosphatidylinositol 3 kinase (PI3K)\/protein kinase B (Akt)\/the mammalian target of rapamycin (mTOR) signaling pathway, demonstrated by western blot analysis. Histopathological assessment verified that empagliflozin suppressed the formation of dysplastic aberrant crypt foci (ACF). Empagliflozin has been suggested to suppress the progression of colorectal carcinogenesis.<\/jats:p>","DOI":"10.1002\/jbt.70886","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T13:32:43Z","timestamp":1778765563000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Unraveling the Potential of Empagliflozin to Counteract 1,2\u2010Dimethylhydrazine\u2010Induced Colorectal Cancer in Rats: Involvement of Redox Imbalance, Inflammatory Cascades, and Unprogrammed Cell Proliferation"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9372-6588","authenticated-orcid":false,"given":"Hager Abd","family":"Al\u2010Hamid","sequence":"first","affiliation":[{"name":"Biochemistry Department, Faculty of Pharmacy Modern University for Technology and Information Cairo 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