Dehydroascorbic acid as pre-conditioner: protection from lipopolysaccharide induced mitochondrial damage

Damon A Lowes, Nigel R Webster, Helen F Galley

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Oxidative stress-induced mitochondrial dysfunction is a common consequence of severe sepsis. However, oxidative stress also activates signalling cascades which enable protection of cells against subsequent oxidative damage. This study hypothesized that cellular uptake of vitamin C as dehydroascorbic acid rather than ascorbic acid would up-regulate antioxidant enzyme systems and impart a protective effect to mitochondria in cells subsequently exposed to lipopolysaccharide (LPS) in an iron free environment. Treatment of monocytes with dehydroascorbic acid, but not ascorbic acid, caused oxidative stress (p < 0.001). Dehydroascorbic acid exposure also resulted in increased manganese superoxide dismutase (p= 0.018) and catalase (p= 0.003) expression. Pre-treatment of monocytes with dehydroascorbic acid followed by LPS resulted in higher mitochondrial membrane potentials than cells without pre-treatment (p < 0.0001). Lower cytochrome c in cytosol (p < 0.05) and higher mitochondrial expression of the anti-apoptotic Bcl-2 protein (p= 0.029) was also found in monocytes pre-treated before subsequent LPS exposure, compared to cells without pre-treatment. In conclusion, acute exposure of monocytes to dehydroascorbic acid in an iron free environment induces cytoprotective antioxidant enzymes and protected mitochondria from the harmful effects of oxidative stress prior to a septic insult, which was abrogated when cells were pre-incubated with the DHA uptake inhibitor cytocholasin B.

Original languageEnglish
Pages (from-to)283-292
Number of pages10
JournalFree Radical Research
Volume44
Issue number3
DOIs
Publication statusPublished - Mar 2010

Keywords

  • vitamin C
  • reactive oxygen species
  • monocyte
  • endotoxin
  • mitochondria
  • pre-conditioning
  • critically-ill patients
  • in-vitro system
  • oxidative stress
  • vitamin-C
  • ascorbic-acid
  • septic shock
  • permeability transition
  • reperfusion injury
  • hydrogen-peroxide
  • skeletal-muscle

Cite this