Potential Role of Empagliflozin to Ameliorate Doxorubicin Induced Cardiotoxicity in Male Rats

Empagliflozin (EMPA), a selective inhibitor of sodium-glucose cotranspoter2 (SGLT2), mainly regulates blood glucose levels. Many different mechanisms illustrated the significant impact on HD with CVs-outcomes that were unexpected. Specialists have speculated that it could be unrelated to lowering BG levels. The study aims to investigate if empagliflozin has promised a protective effect against the cardiotoxicity induced by doxorubicin in laboratory rats. Male Sprague- Dawley-type rats that did not yet have diabetes were randomly allocated to one of four different groups. The control group was given physiological DW (2 mL), the second group was given EMPA, which was given by oral route at a dose of 10 mg per kg, and the DOXO-group was given cumulatively 15 mg/kg of body weight DOXO, given by IP route at a dose of 2.5 mg per kg. The DOXO and EMPA were administered to the EMPA+DOXO group. Doxorubicin caused cardiotoxicity, which was shown by a significant increase (P< 0.001) in the levels of cTn-1, ICAM-1, and caspase-3. At the same time, the levels of GSH and SOD were significantly reduced- (P < 0.001) in the cardiac tissues of rats in the doxorubicin-treated group compared to the control group. The drug also caused Histological changes and lesions. The administration of empagliflozin was found to reduce cardiotoxicity; this can be proved by significant decreases (p~< 0.001) in cTn-1, ICAM-1, and caspase 3 and significant increases (P < 0.001) in SOD and GSH when compared to the DOXO group; and significant improvements (P < 0.001) in the score of CMYO and lesions. In the dosages used in this study, empagliflozin protected the hearts of rats from DOXO-induced cardiotoxicity. This may be related to the interfered^ and ameliorated oxidative stress, the inflammatory response, and the apoptotic pathway.