Metformin Impedes Oxidation of LDL In Vitro

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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More Details
ISSN:19994923
DOI:10.3390/pharmaceutics15082111
Published in:Pharmaceutics
Language:English