Dapagliflozin has protective effects on palmitate-induced renal tubular epithelial cells by enhancing mitochondrial function and reducing oxidative stress.

Abstract

Sodium-glucose co-transporter 2 (SGLT2) inhibitors, commonly utilized for diabetic nephropathy, have demonstrated benefits beyond glucose control, including organ protection. This study investigated the protective effects of the SGLT2 inhibitor, dapagliflozin (DAPA), on palmitate-induced renal tubular epithelial cell (HK-2) injury, particularly concentrating on mitochondrial function and oxidative stress. HK-2 cells were treated with 150 μmol/L palmitate to induce mitochondrial dysfunction and oxidative stress, and they were co-treated with 2 μmol/L DAPA for 24 h. DAPA significantly increased cell viability (P < 0.05), reduced reactive oxygen species (ROS) levels (P < 0.001), and restored mitochondrial membrane potential (P < 0.05). It also lowered malondialdehyde (MDA) level (P < 0.001) and increased superoxide dismutase (SOD) expression level (P < 0.001). Western blot analysis revealed that DAPA reversed palmitate-induced upregulation of apoptosis-related proteins, including Bax and Cytochrome C. DAPA also mitigated the overactivation of autophagy-related proteins, such as LC3 and Beclin-1, indicating its role in modulating autophagy under diabetic nephropathy. Electron microscopy confirmed improvements in mitochondrial morphology, accompanying by reduced swelling and restored cristae structure. These findings highlight the potential of DAPA, as an SGLT2 inhibitor, to mitigate renal injury by enhancing mitochondrial function and reducing oxidative stress, providing novel insights into its therapeutic value for diabetic nephropathy management.