Dapagliflozinin Diyabetik Sıçanlarda Sub-akut Maruziyet Sonrası Renal Etkilerinin Değerlendirilmesi

Abstract

Dapagliflozin (DAPA), a sodium glucose co-transporter 2 (SGLT2) inhibitor, is a therapy option for the treatment of type 2 diabetes. Although several studies have demonstrated its protective effects on the kidney, the FDA warns about the risk of DAPA-induced nephrotoxicity. SGLT2 inhibitors may induce oxidative stress and inflammation in the kidney due to their mechanism of action. In the present study, it was aimed to clarify the molecular effects of DAPA on the kidney. Streptozotocin (STZ)-induced diabetes was initiated by single injection of STZ (35 mg/kg b.w.) after a two-week high-fat diet in male rats. Diabetic rats were administered with DAPA at 10 mg/kg b.w., by oral gavage for 28 days. The oxidative stress, inflammation and apoptosis induction potentials of DAPA were evaluated in kidney homogenates. The morphological changes and apoptosis were investigated by histological examinations. It was observed that DAPA treatment reduced oxidative parameters. The inflammatory mediators increased in diabetic control group, however, this increase was slightly inhibited by DAPA treatment. According to the histological examinations, DAPA ameliorated the diabetes-induced changes and apoptosis. As a result, DAPA showed a protective effect on the kidney by alleviating oxidative stress and inhibiting inflammation and apoptosis. However, further studies are needed to determine the long-term effects of DAPA on the kidney in diabetics by focusing on different mechanisms and individual differences.