Evaluation of Renal Effects of Dapagliflozin in Diabetic Rats with Subacute Exposure

Abstract

ABSTRACT Dapagliflozin (DAPA), a sodium glucose co-transporter 2 (SGLT2) inhibitor, is used 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. Diabetes was induced by single injection of streptozotocin (STZ) (35 mg/kg b.w.) after the rats were fed with high-fat diet for two-weeks. Diabetic rats were administered with DAPA at 10 mg/kg by oral gavage for 28 days. The oxidative stress, inflammation and apoptosis induction potentials of DAPA were evaluated. The morphological changes and apoptosis were investigated by histological examinations. The findings showed that DAPA treatment reduced oxidative parameters and slightly inhibited inflammatory mediator levels. 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 diabetic patients.

Keywords

• Dapagliflozin
• SGLT2 inhibitors
• Nephrotoxicity
• Diabetes
• renoprotective effect

Supporting Institution

Research Fund of Istanbul University

Project Number

TDK-2018-31064

Evaluation of Renal Effects of Dapagliflozin in Diabetic Rats With Subacute Exposure

Abstract

ABSTRACT Dapagliflozin (DAPA), a sodium glucose co-transporter 2 (SGLT2) inhibitor, is used 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. Diabetes was induced by single injection of streptozotocin (STZ) (35 mg/kg b.w.) after the rats were fed with high-fat diet for two-weeks. Diabetic rats were administered with DAPA at 10 mg/kg by oral gavage for 28 days. The oxidative stress, inflammation and apoptosis induction potentials of DAPA were evaluated. The morphological changes and apoptosis were investigated by histological examinations. The findings showed that DAPA treatment reduced oxidative parameters and slightly inhibited inflammatory mediator levels. 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 diabetic patients.

Keywords

• Dapagliflozin
• SGLT2 inhibitors
• nephrotoxicity
• diabetes
• renoprotective effect

Project Number

TDK-2018-31064

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