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The present research aimed to clarify the potential ameliorative effects of secukinumab (SEC) and dapagliflozin (DAPA) against SUN\u2010induced renal toxicity and the underpinning molecular mechanisms. For this purpose, adult Wistar albino rats were received SUN (25\u2009mg\/kg 3 times\/week, <jats:italic>po<\/jats:italic>) and co\u2010treated with SEC (3\u2009mg\/kg\/every 2 weeks, subcutaneously) or DAPA (10\u2009mg\/kg\/day, <jats:italic>po<\/jats:italic>) for 4 weeks and compared with age\u2010matched control group (CON). Markers of kidney functions were assessed in serum samples. Kidneys were harvested for biochemical and histological examination. Compared to CON group, SUN\u2010treated rats displayed signs of kidney dysfunction along with renal histological changes that were ameliorated by SEC or DAPA. Both drugs significantly lowered the renal levels of IL\u201017, but SEC exerted more inhibitory effect than DAPA. Additionally, SUN\u2010subjected rats showed significant increases in the renal expression of NLRP3 inflammasome and the other inflammatory mediators including IL\u20101\u03b2, END\u20101, and MCP\u20101. This was associated with marked decline of the renal levels of beclin\u20101. Co\u2010treatment with SEC or DAPA significantly suppressed NLRP3\u2010induced inflammation while enhanced beclin\u20101\u2010mediated autophagy. The modulatory effect of DAPA on NLRP3 and beclin\u20101 was superior to that of SEC. Moreover, both drugs significantly and similarly attenuated the enhanced cleaved caspase\u20103 expression and interstitial fibrosis in renal tissue of SUN\u2010subjected rats. Collectively, these findings may repurpose SEC and DAPA as candidate therapies to alleviate the renal toxicity of SUN and to rescue the renal functionality in SUN\u2010treated cancer cases.<\/jats:p>","DOI":"10.1002\/jbt.70204","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T04:38:21Z","timestamp":1741754301000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Repurposing Secukinumab and Dapagliflozin as Candidate Therapies to Mitigate the Renal Toxicity of Sunitinib in Rats Through Suppressing IL\u201017\u2010Mediated Pyroptosis and Promoting Autophagy"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8383-8383","authenticated-orcid":false,"given":"Rania A.","family":"Elrashidy","sequence":"first","affiliation":[{"name":"Department of Biochemistry Faculty of Pharmacy, Zagazig University Zagazig Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoda E.","family":"Mohamad","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Faculty of Pharmacy, Zagazig University Zagazig Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara M. 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