Protective Pleiotropic Effect of Flavonoids on NAD + Levels in Endothelial Cells Exposed to High Glucose

NAD+ is important for oxidative metabolism by serving as an electron transporter. Hyperglycemia decreases NAD+ levels by activation of the polyol pathway and by overactivation of poly(ADP-ribose)-polymerase (PARP). We examined the protective role of three structurally related flavonoids (rutin, quer...

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Bibliographic Details
Published in:Oxidative medicine and cellular longevity 2015-01, Vol.2015 (2015), p.1-7
Main Authors: Bast, Aalt, den Hartog, Gertjan J. M., von Ungern-Sternberg, Saskia N. I., Boesten, Daniëlle M. P. H. J.
Format: Article
Language:English
Subjects:
Aldehyde Reductase - metabolism
Animals
Antioxidants
Apoptosis - drug effects
Cell growth
Deoxyribonucleic acid
Diabetes
DNA
DNA repair
Enzymes
Flavones - pharmacology
Flavonoids
Flavonoids - pharmacology
Gene expression
Glucose
Glucose - toxicity
Human Umbilical Vein Endothelial Cells
Humans
Hyperglycemia
Lens, Crystalline - drug effects
Lens, Crystalline - enzymology
NAD - metabolism
Oxidative stress
Pathogenesis
Poly(ADP-ribose) Polymerases - metabolism
Protective Agents - pharmacology
Quercetin - pharmacology
Rodents
Rutin - pharmacology
Swine
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Summary:NAD+ is important for oxidative metabolism by serving as an electron transporter. Hyperglycemia decreases NAD+ levels by activation of the polyol pathway and by overactivation of poly(ADP-ribose)-polymerase (PARP). We examined the protective role of three structurally related flavonoids (rutin, quercetin, and flavone) during high glucose conditions in an in vitro model using human umbilical vein endothelial cells (HUVECs). Additionally we assessed the ability of these flavonoids to inhibit aldose reductase enzyme activity. We have previously shown that flavonoids can inhibit PARP activation. Extending these studies, we here provide evidence that flavonoids are also able to protect endothelial cells against a high glucose induced decrease in NAD+. In addition, we established that flavonoids are able to inhibit aldose reductase, the key enzyme in the polyol pathway. We conclude that this protective effect of flavonoids on NAD+ levels is a combination of the flavonoids ability to inhibit both PARP activation and aldose reductase enzyme activity. This study shows that flavonoids, by a combination of effects, maintain the redox state of the cell during hyperglycemia. This mode of action enables flavonoids to ameliorate diabetic complications.
ISSN:1942-0900
1942-0994
DOI:10.1155/2015/894597