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Rats were allocated to the control group; the CA group was administered CA 10\u2009mg\/kg\/day orally for 10 days; the CDDP group was injected with 7\u2009mg\/kg, intraperitoneal as a single dose on the 5th day, and the CDDP\u2009+\u2009CA group. Compared to the CDDP\u2010treated group, CA effectively attenuated CDDP\u2010induced heart injury as evidenced by a decrease of serum aspartate aminotransferase,\u00a0alkaline phosphatase, creatine kinase\u2010MB, and lactate dehydrogenase enzymes and supported by the alleviation of histopathological changes in cardiac tissues. Biochemically, CA attenuated cardiac oxidative injury through upregulation of the nuclear factor\u2010erythroid 2 related factor 2 (Nrf2) signal. CA suppressed inflammation by decreasing cardiac NO<jats:sub>2<\/jats:sub><jats:sup>\u2212<\/jats:sup>, MPO, iNOS, nuclear factor kappa B\u00a0(NF\u2010\u03baB),\u00a0tumor necrosis factor\u2010alpha, and interleukin 1\u2010beta levels. Besides, CA significantly upregulated cardiac levels of phosphoinositide 3\u2010kinase\u00a0(PI3K), protein kinase B\u00a0(AKT), and p\u2010AKT proteins. Moreover, CA remarkably mitigated CDDP\u2010induced apoptosis via modulation of Bax, cytochrome C, and Bcl\u20102 protein levels. Together, the present study revealed that CA could be a good candidate for preventing CDDP\u2010induced cardiac injury by modulating iNOS\/NF\u2010\u03baB, Nrf2, PI3K\/AKT, and Bax\/cytochrome C\/Bcl\u20102 signals.<\/jats:p>","DOI":"10.1002\/jbt.23309","type":"journal-article","created":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T11:26:27Z","timestamp":1673868387000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Exploring the cardioprotective effects of canagliflozin against cisplatin\u2010induced cardiotoxicity: Role of iNOS\/NF\u2010\u03baB, Nrf2, and Bax\/cytochrome C\/Bcl\u20102 signals"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8341-7458","authenticated-orcid":false,"given":"Fares E. 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