Metformin Impedes Oxidation of LDL In Vitro

被引：6

作者：

Rossmann, Christine ^{[1
]}

Ranz, Cornelia ^{[1
]}

Kager, Gerd ^{[1
]}

Ledinski, Gerhard ^{[1
]}

Koestenberger, Martin ^{[2
]}

Wonisch, Willibald ^{[1
]}

Wagner, Thomas ^{[3
]}

Schwaminger, Sebastian P. ^{[1
,4
]}

Di Geronimo, Bruno ^{[1
]}

Hrzenjak, Andelko ^{[5
]}

Hallstoem, Seth ^{[1
,6
]}

Reibnegger, Gilbert ^{[1
]}

Cvirn, Gerhard ^{[1
]}

Paar, Margret ^{[1
]}

机构：

[1] Med Univ Graz, Otto Loewi Res Ctr, Div Med Chem, A-8010 Graz, Austria

[2] Med Univ Graz, Dept Pediat & Adolescent Med, Div Gen Pediat, A-8010 Graz, Austria

[3] Med Univ Graz, Dept Blood Grp Serol & Transfus Med, A-8010 Graz, Austria

[4] BioTechMed Graz, A-8010 Graz, Austria

[5] Med Univ Graz, Dept Internal Med, Div Pulmonol, A-8010 Graz, Austria

[6] Med Univ Vienna, Div Biomed Res & Translat Med, A-1090 Vienna, Austria

来源：

PHARMACEUTICS | 2023年 / 15卷 / 08期

关键词：

antioxidants; atherosclerosis; diabetes; copper ions; low density lipoprotein; lipid oxidation; LOW-DENSITY-LIPOPROTEIN; PERMANENT CELL-LINE; ENDOTHELIAL DYSFUNCTION; CARDIOVASCULAR OUTCOMES; TYPE-2; ATHEROSCLEROSIS; MODULATION; ACTIVATION; INHIBITION; EXPRESSION;

D O I：

10.3390/pharmaceutics15082111

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页数：14

共 67 条

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