Dehydroascorbic acid

Nature, 1993 Jul 1;364(6432):79-82.

Mammalian facilitative hexose transporters mediate the transport of dehydroascorbic acid.[Reference: WebLink]

Although vitamin C is critical to human physiology, it is not clear how it is taken up into cells. The kinetics of cell and tissue accumulation of ascorbic acid in vitro indicate that the process is mediated by specific transporters at the cell membrane. Some experimental observations have linked the transport of ascorbic acid with hexose transport systems in mammalian cells, although no clear information is available regarding the specific role(s) of these transporters, if any, in this process.
METHODS AND RESULTS:
Here we use the Xenopus laevis oocyte expression system to show that the mammalian facilitative hexose transporters are efficient transporters of the oxidized form of vitamin C (Dehydroascorbic acid). Two transport pathways, one with low affinity and one with high affinity for Dehydroascorbic acid, were found in oocytes expressing the mammalian transporters, and these oocytes accumulated vitamin C against a concentration gradient when supplied with Dehydroascorbic acid. We obtained similar results in experiments using normal human neutrophils.
CONCLUSIONS:
These observations indicate that mammalian facilitative hexose transporters are a physiologically significant pathway for the uptake and accumulation of vitamin C by cells, and suggest a mechanism for the accumulation of ascorbic acid against a concentration gradient.

Free Radical Research, 1997, 27(6):619-626.

Antioxidant and prooxidant effects of ascorbic acid, dehydroascorbic acid and flavonoids on LDL submitted to different degrees of oxidation.[Pubmed: 9455697 ]

Although a high intake of antioxidants may decrease the risk of developing cardiovascular diseases, under certain circumstances they may promote free radical generation and lipid peroxidation.
METHODS AND RESULTS:
The objectives of the present study were to determine the antioxidant effects of ascorbic acid (AA), Dehydroascorbic acid (DHA) and flavonoids on LDL submitted to different degrees of oxidation. LDL was submitted to oxidation with CuCl2 (2.4 microM). Before or at different times after the propagation of the oxidation process, 28 microM (5 micrograms/ml) of either AA or DHA or 5 micrograms/mL flavonoids extract were added. Alpha-tocopherol, conjugated dienes, thiobarbituric acid reacting substances (TBARS) and LDL electrophoretic mobility were determined as indices of LDL oxidation. The presence of any of the three antioxidants from the onset of the incubation delayed the oxidation process. However, the addition of both DHA and flavonoids to the oxidation process when it was already initiated and alpha-tocopherol consumed, accelerated the oxidation. In contrast, AA delayed the oxidation process even when added after alpha-tocopherol was consumed. Nevertheless, it also accelerated LDL oxidation when added during the propagation phase of the oxidation process.
CONCLUSIONS:
although AA, DHA and flavonoids delay LDL oxidation when added before the initiation of the process, they accelerate the process if added to minimally oxidized LDL.

European Journal of Biochemistry, 2010, 255(1):147-155.

Dehydroascorbic acid prevents apoptosis induced by oxidized low-density lipoprotein in human monocyte-derived macrophages.[Pubmed: 9692913]

METHODS AND RESULTS:
Human low-density lipoprotein (LDL) oxidized with Cu2+ or the radical generator 2,2'-azobis(2-methyl-propionamidine) hydrochloride (AAPH) induces apoptosis in mature human monocyte-derived macrophages as assessed by staining with fluorescein-isothiocyanate-labeled annexin V, by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling, and by staining of the 7A6 mitochondrial antigen. Oxidized LDL-induced apoptosis was dose and time dependent and clearly distinct from apoptosis induced by serum deprivation. Human autologous serum and lipoprotein-deficient human serum prevented apoptosis induced by oxidized LDL. Supplementation of serum-free culture medium with 25 microM ascorbic or isoascorbic acid only partially protected macrophages from apoptosis, whereas Dehydroascorbic acid (DHAA) completely inhibited apoptosis induced by either Cu2+- or AAPH-oxidized LDL. Apoptosis was also inhibited by the structural analogue alloxan. Both cyclic multiketones dose-dependently inhibited oxidized LDL-induced apoptosis with IC50 in the submicromolar range. Prior loading of macrophages with ascorbic acid did not prevent the induction of apoptosis. Apoptosis was reduced by more than 90% after treatment of oxidized LDL with DHAA, whereas after incubation with either ascorbic or isoascorbic acid there was no such reduction. Removal of free DHAA by gel filtration did not reverse the inactivation. Parameters of LDL oxidation such as electrophoretic mobility, alpha-tocopherol content, thiobarbituric-acid-reactive subtances and lipid peroxide levels did not correlate to apoptotic activity. Also, binding and uptake of Texas-red-labeled oxidized LDL was not prevented by DHAA. Dithiothreitol-treatment of oxidized LDL, however, reduced the apoptotic activity by 76%.
CONCLUSIONS:
Our results suggest that oxidized thiols on apoB may be essential for the induction of apoptosis by oxidized LDL in human macrophages.

The American Journal of Clinical Nutrition, 01 Apr 1997, 65(4):959-963.

Ascorbic acid and dehydroascorbic acid as biomarkers of oxidative stress caused by smoking.[Pubmed: 9094879 ]

METHODS AND RESULTS:
Using a reliable, newly developed assay for ascorbic acid (reduced form) and Dehydroascorbic acid (DHAA; the oxidized form) in plasma, we studied the influence of age, sex, and smoking on 219 healthy, age-stratified, and randomly selected subjects representing the Danish population. The mean (+/-SD) plasma total ascorbic acid (ascorbic acid + DHAA) concentration was lower in smokers (62.8 +/- 24.9 mumol/L) than in nonsmokers (74.9 +/- 23.6 mumol/L) (P < 0.001) and the DHAA content was 1.8 +/- 4.0% of the total ascorbic acid in smokers compared with 0.1 +/- 3.1% in nonsmokers (P < 0.001). A significant inverse correlation between the DHAA fraction and the total ascorbic acid concentration was found in smokers (P < 0.002) but not in smokers; the slopes of the linear regressions were significantly different in the two groups (P < 0.005). The mean plasma concentration of total ascorbic acid was higher in females than in males (P < 0.005); this difference persisted in multivariate analysis when smoking was adjusted for. No age dependence could be identified. The data show that smoking results in severe oxidative stress, depletion of the ascorbic acid pool, and insufficient reduction capacity to maintain ascorbic acid in the reduced form in plasma.
CONCLUSIONS:
We suggest that the additional analysis of DHAA allows further differentiation in the assessment of oxidative stress and may provide an objective way of determining vitamin C requirements in smokers. Preliminary findings suggest that a vitamin C dose that results in a plasma concentration of approximately 70 mumol/L or higher is required in smokers.

Neurochemistry International,2005,46( 5):399-407.

Dehydroascorbic acid normalizes several markers of oxidative stress and inflammation in acute hyperglycemic focal cerebral ischemia in the rat.[Reference: WebLink]

METHODS AND RESULTS:
We investigated the effect of Dehydroascorbic acid (DHA), the oxidized form of vitamin C which is a superoxide scavenger, on manganese superoxide dismutase (MnSOD), copper–zinc SOD (CuZnSOD), cyclooxygenase-2 (COX-2) and interleukin-1beta (IL-1β) expression in a rat model of focal cerebral ischemia under normo- and hyperglycemic conditions. Edema formation was also assessed. MnSOD, CuZnSOD, COX-2 and IL-1β mRNA and protein expression were studied 3 h post-ischemia. No changes were observed in MnSOD and CuZnSOD mRNA expression among the groups. COX-2 and IL-1β mRNA expression were upregulated by ischemia but were not influenced by the glycemic state. At the protein level, hyperglycemic cerebral ischemia increased MnSOD and CuZnSOD [Bémeur, C., Ste-Marie, L., Desjardins, P., Butterworth, R.F., Vachon, L., Montgomery, J., Hazell, A.S., 2004a. Expression of superoxide dismutase in hyperglycemic focal cerebral ischemia in the rat. Neurochem. Int. 45, 1167–1174] and IL-1β expression compared to normoglycemic ischemia. COX-2 protein expression was also significantly higher following hyperglycemic ischemia compared to hyperglycemic shams. DHA administration did not change the pattern of COX-2 or IL-1β mRNA expression, but normalized the increased protein expression following hyperglycemic ischemia. DHA administration also normalized MnSOD and CuZnSOD protein expression to the levels observed in normoglycemic ischemic animals. Edema formation was significantly reduced by DHA administration in hyperglycemic ischemic animals.
CONCLUSIONS:
The DHA-induced post-transcriptional normalization of MnSOD, CuZnSOD, COX-2 and IL-1β levels and the decreased edema formation suggest that hyperglycemia accelerates superoxide formation and the inflammatory response, thus contributing to early damage in hyperglycemic stroke and strategies to scavenge superoxide should be an important therapeutic avenue.