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En Face Detection of Nitric Oxide and Superoxide in Endothelial Layer of Intact Arteries
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Nitrones reverse hyperglycemia-induced endothelial dysfunction in bovine aortic endothelial cells.

Colwyn A Headley1, David DiSilvestro2, Kelsey E Bryant3

  • 1Department of Biological Chemistry and Pharmacology, The Ohio State University, Columbus, OH, USA.

Biochemical Pharmacology
|January 18, 2016
PubMed
Summary

Nitrone spin traps like PBN and DMPO effectively reversed hyperglycemia-induced endothelial dysfunction in bovine aortic endothelial cells, improving cell health and function. Further in vivo studies are recommended for cardiometabolic disease models.

Keywords:
5,5-dimethyl-1-pyrroline N-oxide (PubChem ID: 1774)Endothelial dysfunctionHyperglycemiaN-tert-butyl-α-phenylnitrone (PubChem ID: 638877)NOROSα-lipoic acid (PubChem ID: 864)

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Cardiovascular Research

Background:

  • Hyperglycemia contributes to endothelial dysfunction via increased reactive oxygen species (ROS).
  • Nitrones are known to counteract ROS-induced damage and restore endothelial function.

Purpose of the Study:

  • To investigate the efficacy of nitrone spin traps (DMPO, PBN, PBN-LA) in an in vitro model of hyperglycemia-induced endothelial dysfunction.
  • To assess their impact on glucose uptake and markers of oxidative stress and mitochondrial function.

Main Methods:

  • Bovine aortic endothelial cells (BAEC) were cultured under low (5.5mM) and high (50mM) glucose conditions for 14 days.
  • Cells were treated with nitrones (DMPO, PBN, PBN-LA) for 24 hours post-hyperglycemic culture.
  • Measurements included cell viability, ROS levels, nitric oxide (NO) and tetrahydrobiopterin (BH4) levels, mitochondrial membrane potential, glucose transport, and antioxidant enzyme activity.

Main Results:

  • Chronic hyperglycemia significantly increased ROS, decreased cell viability, reduced NO bioavailability and BH4 levels, and impaired glucose transport and superoxide dismutase (SOD) activity.
  • Treatment with PBN and DMPO (50 μM) normalized most measured parameters, except for SOD and catalase activities.
  • Nitrone treatment mitigated the negative effects of high glucose on endothelial cells.

Conclusions:

  • Nitrone compounds PBN and DMPO effectively reverse hyperglycemia-induced endothelial dysfunction in vitro.
  • These findings support further investigation of nitrones in animal models of cardiometabolic diseases.