alpha-Lipoic acid and ascorbate prevent LDL oxidation and oxidant stress in endothelial cells

Mol Cell Biochem. 2008 Feb;309(1-2):125-32. doi: 10.1007/s11010-007-9650-z. Epub 2007 Nov 16.


Both alpha-lipoic acid (LA) and ascorbic acid (vitamin C) have been shown to improve endothelial dysfunction, a precursor of atherosclerosis. Since oxidant stress can cause endothelial dysfunction, we tested the interaction and efficacy of these antioxidants in preventing oxidant damage to lipids due to both intra- and extracellular oxidant stresses in EA.hy926 endothelial cells. LA spared intracellular ascorbate in culture and in response to an intracellular oxidant stress induced by the redox cycling agent menadione. Extracellular oxidant stress generated by incubating cells for 2 h in with 0.2 mg/ml LDL and 5 muM Cu2+ caused a time-dependent increase of the lipid peroxidation product malondialdehyde in both cells and LDL, preceded by rapid disappearance of; alpha-tocopherol in LDL. alpha-Lipoic acid at concentrations of 40-80 microM blunted these effects. Similarly, intracellular ascorbate concentrations of 1-2 mM also prevented Cu2+-induced lipid peroxidation in LDL and cells. Cu2+-dependent oxidation of LDL in the presence of ascorbate-loaded cells decreased intracellular ascorbate by 20%, but this decrease was not reversed by LA. Both LA and ascorbate protect endothelial cells and LDL from either intra- or extracellular oxidant stress, but that LA does not spare ascorbate in oxidatively stressed cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Ascorbic Acid / metabolism*
  • Cells, Cultured
  • Cholesterol, LDL / metabolism*
  • Copper / metabolism
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism*
  • Extracellular Space / drug effects
  • Extracellular Space / metabolism
  • Glutathione / metabolism
  • Humans
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism
  • Malondialdehyde / metabolism
  • Oxidants / pharmacology
  • Oxidation-Reduction / drug effects
  • Oxidative Stress / drug effects*
  • Thioctic Acid / pharmacology*
  • Time Factors
  • Vitamin K 3 / pharmacology
  • alpha-Tocopherol / metabolism


  • Cholesterol, LDL
  • Oxidants
  • Malondialdehyde
  • Vitamin K 3
  • Thioctic Acid
  • Copper
  • Glutathione
  • alpha-Tocopherol
  • Ascorbic Acid