Evaluation of the Cardioprotective Activity of Empagliflozin, Linagliptin and Their Combination Against Doxorubicin-Induced Cardiotoxicity in Rats

Background Doxorubicin is an effective antineoplastic agent whose clinical application may be limited by cardiotoxicity. The present study was undertaken to evaluate the cardioprotective activity of empagliflozin and linagliptin, administered individually and in combination, against doxorubicin-induced cardiotoxicity in rats.Materials and MethodsHealthy adult male Wistar rats weighing 180–225 g were used. Doxorubicin was administered intraperitoneally at 2.5 mg/kg in six equal doses on alternate days over two weeks, giving a cumulative dose of 15 mg/kg. Empagliflozin (10 mg/kg/day, orally) and linagliptin (5 mg/kg/day, orally) were administered for 15 days, either individually or in combination. Vitamin E (100 mg/kg, orally) was used as the standard treatment. Serum glucose, CK-MB, LDH, total cholesterol, triglycerides, HDL-C, LDL-C, VLDL-C and cardiac troponin I were evaluated. Histopathological examination of cardiac tissue was also performed. ResultsDoxorubicin-induced cardiotoxicity produced marked biochemical and histopathological alterations. CK-MB increased from 18.50 ± 1.190 U/L in the normal control group to 27.50 ± 1.443 U/L in the disease control group, while LDH increased from 175.00 ± 6.445 to 220.00 ± 12.25 U/L. Treatment with empagliflozin, linagliptin and their combination reduced reported CK-MB levels to 21.50 ± 1.323, 23.50 ± 1.190 and 19.75 ± 0.8539 U/L, respectively. Cardiac troponin I was 4.50 ng/mL in the disease control group and was reported as 3.11, 2.67 and 2.01 ng/mL in the empagliflozin, linagliptin and combination groups, respectivelyConclusionThe present findings indicate that empagliflozin and linagliptin individually attenuated selected biochemical and histopathological alterations associated with doxorubicin-induced cardiotoxicity. Further mechanistic and functional studies are required to establish the mechanisms underlying these observations