Therapeutic efficacy of dapagliflozin on diabetic kidney disease in rats

Abstract

AimDiabetic kidney disease (DKD) is one of the severe microvascular complications of type 2 diabetes mellitus (T2DM), which eventually leads to irreversible renal damage and develops into end-stage renal disease (ESRD). Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a new class of antidiabetic drugs that act on the kidney to reduce glucose reabsorption. Increasing evidence confirms that dapagliflozin exerts a protective effect on DKD, but the mechanisms have not been reported. The aims of this study were to observe the therapeutic efficacy of dapagliflozin on DKD and investigate the possible immunological mechanism. Materials and methodsT2DM was modeled by a high-sugar and high-fat diet combined with STZ. Then, rats were treated with 10 mg/kg dapagliflozin for 8 weeks. The protective efficacy of dapagliflozin was evaluated by observing body weight, blood glucose, blood serum creatinine, blood urea nitrogen, 24-h urine protein, renal histology and ultrastructure, and oxidative stress levels. The immunological mechanisms were monitored by measuring the levels of TLR2/Myd88/NF-κB by immunohistochemical staining, RT-qPCR and Western blotting. ResultsAfter treatment with dapagliflozin, renal damage was greatly improved. The levels of blood glucose, renal function and proteinuria were significantly decreased, and renal pathological and ultrastructural damage was obviously extenuated, possibly due to the reduction in inflammation and the levels of oxidative stress. ConclusionsDapagliflozin has therapeutic potential for DKD. This effect was possibly mediated by inhibiting inflammation and oxidative stress levels.