TY - JOUR A1 - Baer, Patrick C. A1 - Koch, Benjamin Florian A1 - Freitag, Janina A1 - Schubert, Ralf A1 - Geiger, Helmut T1 - No cytotoxic and inflammatory effects of empagliflozin and dapagliflozin on primary renal proximal tubular epithelial cells under diabetic conditions in vitro T2 - International journal of molecular sciences N2 - 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. KW - renal tubular cells KW - epithelial cells KW - proximal tubule KW - cytotoxicity KW - injury KW - inflammation KW - empagliflozin KW - dapagliflozin KW - kidney Y1 - 2020 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/54290 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-542901 SN - 1422-0067 SN - 1661-6596 N1 - This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited VL - 21 IS - 2, Art. 391 SP - 1 EP - 15 PB - Molecular Diversity Preservation International CY - Basel ER -