No Cytotoxic and Inflammatory Effects of Empagliflozin and Dapagliflozin on Primary Renal Proximal Tubular Epithelial Cells under Diabetic Conditions In Vitro

International Journal of Molecular Sciences

Ralf Schubert¹  Helmut Geiger²  PatrickC. Baer²  Benjamin Koch²  Janina Freitag² 

[1] Division of Allergology, Pneumology and Cystic Fibrosis, Department for Children and Adolescents, University Hospital, Goethe-University, 60596 Frankfurt/M., Germany;Division of Nephrology, Department of Internal Medicine III, University Hospital, Goethe-University, 60596 Frankfurt/M., Germany;

关键词: renal tubular cells;    epithelial cells;    proximal tubule;    cytotoxicity;    injury;    inflammation;    empagliflozin;    dapagliflozin;    kidney;   

DOI  :  10.3390/ijms21020391

来源: DOAJ

【 摘 要 】

Gliflozins are inhibitors of the renal proximal tubular sodium-glucose co-transporter-2 (SGLT-2), that inhibit reabsorption of urinary glucose and they are able to reduce hyperglycemia in patients with type 2 diabetes. A renoprotective function of gliflozins has been proven in diabetic nephropathy, but harmful side effects on the kidney have also been described. In the current project, primary highly purified human renal proximal tubular epithelial cells (PTCs) have been shown to express functional SGLT-2, and were used as an in vitro model to study possible cellular damage induced by two therapeutically used gliflozins: empagliflozin and dapagliflozin. Cell viability, proliferation, and cytotoxicity assays revealed that neither empagliflozin nor dapagliflozin induce effects in PTCs cultured in a hyperglycemic environment, or in co-medication with ramipril or hydro-chloro-thiazide. Oxidative stress was significantly lowered by dapagliflozin but not by empagliflozin. No effect of either inhibitor could be detected on mRNA and protein expression of the pro-inflammatory cytokine interleukin-6 and the renal injury markers KIM-1 and NGAL. In conclusion, empa- and dapagliflozin in therapeutic concentrations were shown to induce no direct cell injury in cultured primary renal PTCs in hyperglycemic conditions.

【 授权许可】

Unknown