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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Rossmann, C; Ranz, C; Kager, G; Ledinski, G; Koestenberger, M; Wonisch, W; Wagner, T; Schwaminger, SP; Di, Geronimo, B; Hrzenjak, A; Hallstöm, S; Reibnegger, G; Cvirn, G; Paar, M.
Metformin Impedes Oxidation of LDL In Vitro.
Pharmaceutics. 2023; 15(8): Doi: 10.3390/pharmaceutics15082111 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Führende Autor*innen der Med Uni Graz
Cvirn Gerhard
Rossmann Christine Renate
Co-Autor*innen der Med Uni Graz
Di Geronimo Quintero Bruno
Hallström Seth
Hrzenjak Andelko
Kager Gerd
Koestenberger Martin
Ledinski Gerhard
Paar Margret
Reibnegger Gilbert
Schwaminger Sebastian
Wagner Thomas
Wonisch Willibald
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Abstract:
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.

Find related publications in this database (Keywords)
antioxidants
atherosclerosis
diabetes
copper ions
low density lipoprotein
lipid oxidation
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