Alpha lipoic acid attenuates microvascular endothelial cell hyperpermeability by inhibiting the intrinsic apoptotic signaling

Am J Surg. 2008 Feb;195(2):174-8. doi: 10.1016/j.amjsurg.2007.09.028.


Background: This study examined whether alpha lipoic acid (ALA), an antioxidant with anti-apoptotic properties, synthesized in mitochondria of endothelial cells, would inhibit intrinsic apoptotic signaling and microvascular endothelial cell hyperpermeability.

Methods: Rat lung microvascular endothelial cells were transfected with BAK (BH3) peptide (5 microg/mL) or active caspase-3 (5 microg/mL) and were pretreated with ALA (10 and 100 micromol/L). Hyperpermeability was determined using fluorescein isothiocyanate albumin-flux across the cells grown as monolayer. Reactive oxygen species (ROS) formation was determined using 123 dihydrorhodamine and mitochondrial membrane potential using JC-1. Cytochrome c levels and caspase-3 activity were determined using an enzyme-linked immunosorbent assay and a fluorometric assay, respectively.

Results: ALA (100 micromol/L) pretreatment attenuated BAK (BH3)-induced hyperpermeability and ROS formation. ALA restored BAK (BH3)-induced collapse in mitochondrial membrane potential and decreased BAK (BH3)-induced cytochrome c release and caspase-3 activity.

Conclusions: These findings suggest that ALA attenuates BAK-induced monolayer hyperpermeability through the inhibition of ROS formation and intrinsic apoptotic signaling.

MeSH terms

  • Analysis of Variance
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Capillary Permeability
  • Caspase 3 / metabolism
  • Cell Membrane Permeability / drug effects
  • Cell Membrane Permeability / physiology*
  • Cell Survival
  • Cells, Cultured
  • Cytochromes c / metabolism
  • Disease Models, Animal
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism*
  • Lung / cytology
  • Membrane Potential, Mitochondrial / drug effects
  • Membrane Potential, Mitochondrial / physiology
  • Probability
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism*
  • Sensitivity and Specificity
  • Signal Transduction
  • Thioctic Acid / metabolism*
  • Thioctic Acid / pharmacology


  • Reactive Oxygen Species
  • Thioctic Acid
  • Cytochromes c
  • Caspase 3