Cardiac effects of dapagliflozin in diabetic rats with subacute exposure

Abstract

Background and Aims: Dapagliflozin (DAPA) is a sodium-glucose co-transporter 2 (SGLT2) inhibitor used for the treatment of type 2 diabetes mellitus (T2DM) as a monotherapy or combination therapy with other antidiabetic medicines. The Food and Drug Administration (FDA) recently approved DAPA to minimize the risk of hospitalization due to heart failure in patients with T2DM because of its antihypertensive and antihyperglycemic activities. However, further study of DAPA is necessary to ensure the safety of patients. Methods: T2DM was induced by streptozotocin (STZ) injection (35 mg/kg b.w. i.p.) in male rats that were fed a high-fat diet for two weeks before STZ injection. The diabetic rats were exposed to 10 mg/kg DAPA by oral gavage during sub-acute treat- ment. Total cholesterol levels and oxidative stress parameters were evaluated. Heart tissues were histologically examined, and cardiac troponin T (cTnT) levels were measured. Results: DAPA has the potential to inhibit diabetes-induced oxidative stress and morphologic damage to heart tissue, and increased cTnT levels of the heart, which is important for cardiac contractility. Conclusion: DAPA might have a protective effect on the heart at a 10 mg/kg oral dose; however, further experimental and clinical studies are required to clarify the cardio-protective potential of DAPA.