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

Area of Science:

• Biochemistry
• Cell Biology
• Immunology

Background:

• Severe sepsis often leads to mitochondrial dysfunction due to oxidative stress.
• Oxidative stress can also trigger protective cellular signaling pathways.
• Vitamin C's role in cellular protection against oxidative damage is under investigation.

Purpose of the Study:

• To investigate if dehydroascorbic acid (DHA), a form of vitamin C, up-regulates antioxidant enzymes.
• To determine if DHA protects mitochondria from oxidative stress induced by lipopolysaccharide (LPS).
• To compare the effects of DHA versus ascorbic acid on cellular protection.

Main Methods:

• Monocytes were treated with dehydroascorbic acid (DHA) or ascorbic acid in an iron-free environment.
• Cellular oxidative stress, antioxidant enzyme expression (manganese superoxide dismutase, catalase), and mitochondrial membrane potential were measured.
• Mitochondrial and cytosolic cytochrome c levels, and Bcl-2 protein expression were assessed following LPS exposure.

Main Results:

• Dehydroascorbic acid (DHA) treatment induced oxidative stress and increased manganese superoxide dismutase and catalase expression in monocytes.
• Pre-treatment with DHA significantly enhanced mitochondrial membrane potential and reduced cytochrome c in the cytosol after LPS exposure.
• DHA pre-treatment also increased mitochondrial Bcl-2 protein expression, indicating anti-apoptotic effects, which were blocked by a DHA uptake inhibitor.

Conclusions:

• Acute exposure to dehydroascorbic acid (DHA) in monocytes induces protective antioxidant enzymes.
• DHA pre-treatment protects mitochondria from oxidative stress associated with a septic insult (LPS).
• The protective effects of DHA are dependent on its cellular uptake.