Metformin decreases intracellular production of reactive oxygen species in aortic endothelial cells.
Beyond its antidiabetic activity justifying its use in the treatment of the type 2 diabetes, metformin (MET [dimethylguanidine, Glucophage]) has been shown to exhibit antioxidant properties in vitro, which could contribute to limit the deleterious vascular complications of diabetes. We investigated whether MET, at the pharmacological level of 10 -5 mol/L, was able to modulate intracellular production of reactive oxygen species (ROS) both in quiescent bovine aortic endothelial cells (BAECs) and in BAECs stimulated by a short incubation with high levels of glucose (30 mmol/L, 2 hours) or angiotensin II (10 -7 mol/L, 1 hour). Intracellular ROS production was measured by fluorescence of the DCF (2,7-dichlorodihydrofluorescein) probe. Our results showed that MET was able to reduce the intracellular production of ROS in both nonstimulated BAECs (-20%, P < .05) and BAEC stimulated by high levels of glucose or angiotensin II (-28% and -72%, respectively, P < .01). Experiments performed in the presence of the nicotinamide adenine dinucleotide phosphate [NAD(P)H] oxidase inhibitor apocynin or the respiratory mitochondrial chain inhibitor rotenone indicated that MET exerted its effect partly through an inhibition of the formation of ROS produced mainly by NAD(P)H oxidase and also, to a lesser extent, by the respiratory mitochondrial chain.
Ouslimani
Nadjat
N
EA 3617 "Stress oxydant et atteintes vasculaires," Département de Biochimie, Faculté de Pharmacie, F75006 Paris, France.
Peynet
Jacqueline
J
Bonnefont-Rousselot
Dominique
D
Thérond
Patrice
P
Legrand
Alain
A
Beaudeux
Jean-Louis
JL
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008687:Metformin / Q000494:pharmacology*; D019255:NADPH Oxidases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*
D007004:Hypoglycemic Agents; D017382:Reactive Oxygen Species; D008687:Metformin; D019255:NADPH Oxidases