Background: Diabetes patients often suffer chronic vascular complications resulting from endothelial dysfunction, smooth muscle cell (SMC) proliferation, inflammation and disturbed oxidative balance. Empagliflozin is one of three approved sodium-glucose cotransporter 2 (SGLT2) inhibitors for type 2 diabetes mellitus.
The aim of this study: was to determine the protective and repairing effect of EMPA in a model of vascular endothelial and SMC damage with 25-hydroxycholesterol (25-OHC).
Methods: Human umbilical vascular endothelial cells (HUVECs) and SMCs were treated with compounds which induce DNA single-strand breaks (SSBs) and subjected to comet assay. Oxidative DNA damage was detected using endonuclease III (Nth) or human 8 oxoguanine DNA glycosylase (hOOG1). Reactive oxygen species (ROS) formation was determined by the fluorescence of a 6-carboxy-2',7'-dichlorodihydrofluoresce probe in diacetate (H2DCFDA).
Results: 25-OHC-stimulated SMCs showed greater resistance to ROS generation and DNA damage compared to HUVECs. In both experimental models, EMPA treatment was associated with lower ROS production and DNA damage, including oxidative damage to purines and pyrimidines. This effect was not dose-dependent. EMPA was found to counteract this DNA damage by inhibiting ROS production.
Conclusions: It appears that the EMPA induced indirect repair of DNA by inhibiting ROS production.
Keywords: DNA bases; DNA oxidative damage; Empagliflozin; Oxidized cholesterol; Reactive oxygen species; Smooth muscle cells; Vascular endothelial damage.
Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.