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 language | English |
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Pages (from-to) | 283-292 |
Number of pages | 10 |
Journal | Free Radical Research |
Volume | 44 |
Issue number | 3 |
DOIs | |
Publication status | Published - 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