Oxygen: from the benefits of inducing VEGF expression to managing the risk of hyperbaric stress

Antioxid Redox Signal. 2005 Sep-Oct;7(9-10):1377-87. doi: 10.1089/ars.2005.7.1377.


Hypoxia limits wound healing. Both normobaric (1 atm) and hyperbaric oxygen (HBO) approaches have been used clinically to oxygenate wound tissue. Recently, we reported that HBO ameliorates stress-induced impairment of dermal healing. We examined the effect of pressure on oxygen-induced vascular endothelial growth factor (VEGF) expression by human HaCaT keratinocytes. Next, we investigated the effect of HBO on whole-body redox and on the ratio of oxidized to reduced glutathione (GSSG/GSH) in the liver, heart, lung, and brain of rats. Superoxygenation (90% O2) of keratinocytes partially arrested cell growth. G2-M growth arrest was substantially augmented by HBO. HBO also caused apoptosis in a small subpopulation. Normobaric oxygen, but not HBO (2 atm), potently induced the expression of VEGF165 and 189. In vivo electron paramagnetic resonance spectroscopy imaging revealed a clear shift of the whole-body redox status toward oxidation in response to HBO. The standard diet of laboratory rats contains excessive (17x human recommended dietary allowance) alpha-tocopherol (E++), which confers exceptional resistance to oxidant insults. People with chronic wounds commonly suffer from under- or malnutrition. We generated vitamin E-deficient (E-) rats by long-term dietary vitamin E restriction. HBO did not raise GSSG/GSH in E++ rats, but post-HBO GSSG/GSH was significantly higher in E- compared with E++. Thus, rats on antioxidant-enriched diet were well protected against HBO. The risk of oxidative stress may negatively impact the net benefits of HBO. This is of special concern for people with inadequate intake of dietary antioxidants. Nutritional antioxidant supplementation may offset HBO-induced oxidative stress.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Cell Cycle
  • Cell Division
  • Cell Line
  • Chromatography, High Pressure Liquid
  • Electron Spin Resonance Spectroscopy
  • Female
  • G2 Phase
  • Glutathione / metabolism
  • Humans
  • Hyperbaric Oxygenation / adverse effects*
  • Keratinocytes / cytology
  • Keratinocytes / metabolism
  • Keratinocytes / pathology
  • Liver / metabolism
  • Oxidants / chemistry
  • Oxidation-Reduction
  • Oxidative Stress*
  • Oxygen / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Risk
  • Time Factors
  • Vascular Endothelial Growth Factor A / biosynthesis*
  • Vascular Endothelial Growth Factor A / metabolism
  • Vitamin E / metabolism
  • Wound Healing
  • alpha-Tocopherol / metabolism


  • Antioxidants
  • Oxidants
  • Vascular Endothelial Growth Factor A
  • Vitamin E
  • Glutathione
  • alpha-Tocopherol
  • Oxygen