The protective effects of empagliflozin on DNA oxidative changes in a model of vascular endothelial and smooth muscle cells damaged by oxidized cholesterol.
DNA bases
DNA oxidative damage
Empagliflozin
Oxidized cholesterol
Reactive oxygen species
Smooth muscle cells
Vascular endothelial damage
Journal
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
ISSN: 1950-6007
Titre abrégé: Biomed Pharmacother
Pays: France
ID NLM: 8213295
Informations de publication
Date de publication:
27 Dec 2023
27 Dec 2023
Historique:
received:
17
10
2023
revised:
19
12
2023
accepted:
21
12
2023
medline:
29
12
2023
pubmed:
29
12
2023
entrez:
28
12
2023
Statut:
aheadofprint
Résumé
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. was to determine the protective and repairing effect of EMPA in a model of vascular endothelial and SMC damage with 25-hydroxycholesterol (25-OHC). 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 (H 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. It appears that the EMPA induced indirect repair of DNA by inhibiting ROS production.
Sections du résumé
BACKGROUND
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
OBJECTIVE
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
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 (H
RESULTS
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
CONCLUSIONS
It appears that the EMPA induced indirect repair of DNA by inhibiting ROS production.
Identifiants
pubmed: 38154272
pii: S0753-3322(23)01863-2
doi: 10.1016/j.biopha.2023.116065
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
116065Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.