Oxyresveratrol and/or Dapagliflozin Attenuate Doxorubicin-Induced Nephrotoxicity via Modulation of PPAR-γ/Nrf-2/HO-1, NF-κB/TNF-α/Keap-1, and Bcl-2/Caspase-3/ATG-5 signaling pathways in rats

Among the most undesirable effects that lead to the restriction of doxorubicin (DOX) use in chemotherapy is kidney damage. This research aimed to assess the possible defenses against DOX-induced nephrotoxicity offered by oxyresveratrol (ORES) and/or dapagliflozin (DAPA). Five groups of eight male Swiss albino rats each were created from a total of sixty-four. One intravenous injection of DOX (10 mg/kg) was given into the tail vein on the fourteenth day of the experiment; in the meantime, ORES (80 mg/kg) and DAPA (10 mg/kg) were given orally 14 days prior to the DOX injection and 2 days following the DOX injection. In rats given DOX, ORES and/or DAPA both successfully reduced the kidney weight, kidney/bodyweight ratio, and blood levels of creatinine, uric acid, and urea. They also increased final body weight and albumin serum levels. Additionally, lower serum concentrations of TNF-α and IL-6 were noted, along with a lower kidney content of caspase-3. Furthermore, the expression of the Bcl-2 gene was upregulated, as were the Nrf-2, PPAR-γ, and HO-1 proteins, and there was a downregulation of the ATG-5, Keap-1, and NF-κB renal gene expression. These findings support a decrease in oxidative stress and relief of histopathological alterations. The current study's findings suggest that ORES and/or DAPA pretreatment could be a viable therapeutic approach to ameliorate DOX-induced nephrotoxicity.