No cytotoxic and inflammatory effects of empagliflozin and dapagliflozin on primary renal proximal tubular epithelial cells under diabetic conditions in vitro

  • 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.

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Author:Patrick C. BaerORCiDGND, Benjamin Florian KochORCiDGND, Janina Freitag, Ralf SchubertORCiDGND, Helmut GeigerGND
URN:urn:nbn:de:hebis:30:3-542901
DOI:https://doi.org/10.3390/ijms21020391
ISSN:1422-0067
ISSN:1661-6596
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/31936266
Parent Title (English):International journal of molecular sciences
Publisher:Molecular Diversity Preservation International
Place of publication:Basel
Document Type:Article
Language:English
Year of Completion:2020
Date of first Publication:2020/01/08
Publishing Institution:Universit├Ątsbibliothek Johann Christian Senckenberg
Release Date:2020/07/22
Tag:cytotoxicity; dapagliflozin; empagliflozin; epithelial cells; inflammation; injury; kidney; proximal tubule; renal tubular cells
Volume:21
Issue:2, Art. 391
Page Number:15
First Page:1
Last Page:15
Note:
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
HeBIS-PPN:467515301
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universit├Ątspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0