Bibliographic Details
Title: |
Metformin Impedes Oxidation of LDL In Vitro |
Authors: |
Christine Rossmann, Cornelia Ranz, Gerd Kager, Gerhard Ledinski, Martin Koestenberger, Willibald Wonisch, Thomas Wagner, Sebastian P. Schwaminger, Bruno Di Geronimo, Andelko Hrzenjak, Seth Hallstöm, Gilbert Reibnegger, Gerhard Cvirn, Margret Paar |
Source: |
Pharmaceutics, Vol 15, Iss 8, p 2111 (2023) |
Publisher Information: |
MDPI AG, 2023. |
Publication Year: |
2023 |
Collection: |
LCC:Pharmacy and materia medica |
Subject Terms: |
antioxidants, atherosclerosis, diabetes, copper ions, low density lipoprotein, lipid oxidation, Pharmacy and materia medica, RS1-441 |
More Details: |
Metformin is the most commonly prescribed glucose-lowering drug for the treatment of type 2 diabetes. The aim of this study was to investigate whether metformin is capable of impeding the oxidation of LDL, a crucial step in the development of endothelial dysfunction and atherosclerosis. LDL was oxidized by addition of CuCl2 in the presence of increasing concentrations of metformin. The extent of LDL oxidation was assessed by measuring lipid hydroperoxide and malondialdehyde concentrations, relative electrophoretic mobilities, and oxidation-specific immune epitopes. Cytotoxicity of oxLDL in the vascular endothelial cell line EA.hy926 was assessed using the alamarBlue viability test. Quantum chemical calculations were performed to determine free energies of reactions between metformin and radicals typical for lipid oxidation. Metformin concentration-dependently impeded the formation of lipid hydroperoxides, malondialdehyde, and oxidation-specific immune epitopes when oxidation of LDL was initiated by addition of Cu2+. The cytotoxicity of oxLDL was reduced when it was obtained under increasing concentrations of metformin. The quantum chemical calculations revealed that only the reaction of metformin with hydroxyl radicals is exergonic, whereas the reactions with hydroperoxyl radicals or superoxide radical anions are endergonic. Metformin, beside its glucose-lowering effect, might be a suitable agent to impede the development of atherosclerosis and associated CVD. This is due to its capability to impede LDL oxidation, most likely by scavenging hydroxyl radicals. |
Document Type: |
article |
File Description: |
electronic resource |
Language: |
English |
ISSN: |
1999-4923 |
Relation: |
https://www.mdpi.com/1999-4923/15/8/2111; https://doaj.org/toc/1999-4923 |
DOI: |
10.3390/pharmaceutics15082111 |
Access URL: |
https://doaj.org/article/9bbf4f263d38442cb03d53efcf102673 |
Accession Number: |
edsdoj.9bbf4f263d38442cb03d53efcf102673 |
Database: |
Directory of Open Access Journals |
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