Skip to main content Accessibility help
×
×
Home

Vitamin C deficiency in weanling guinea pigs: differential expression of oxidative stress and DNA repair in liver and brain

  • Jens Lykkesfeldt (a1), Gilberto Perez Trueba (a2), Henrik E. Poulsen (a2) and Stephan Christen (a3)

Abstract

Neonates are particularly susceptible to malnutrition due to their limited reserves of micronutrients and their rapid growth. In the present study, we examined the effect of vitamin C deficiency on markers of oxidative stress in plasma, liver and brain of weanling guinea pigs. Vitamin C deficiency caused rapid and significant depletion of ascorbate (P < 0·001), tocopherols (P < 0·001) and glutathione (P < 0·001), and a decrease in superoxide dismutase activity (P = 0·005) in the liver, while protein oxidation was significantly increased (P = 0·011). No changes in lipid oxidation or oxidatively damaged DNA were observed in this tissue. In the brain, the pattern was markedly different. Of the measured antioxidants, only ascorbate was significantly depleted (P < 0·001), but in contrast to the liver, ascorbate oxidation (P = 0·034), lipid oxidation (P < 0·001), DNA oxidation (P = 0·13) and DNA incision repair (P = 0·014) were all increased, while protein oxidation decreased (P = 0·003). The results show that the selective preservation of brain ascorbate and induction of DNA repair in vitamin C-deficient weanling guinea pigs is not sufficient to prevent oxidative damage. Vitamin C deficiency may therefore be particularly adverse during the neonatal period.

Copyright

Corresponding author

*Corresponding author: Dr Jens Lykkesfeldt, fax +45 35 35 35 14, email jopl@life.ku.dk

References

Hide All
1Guesry, P (1998) The role of nutrition in brain development. Prev Med 27, 189194.
2Morgane, PJ, Austin-LaFrance, R, Bronzino, J, Tonkiss, J, az-Cintra, S, Cintra, L, Kemper, T & Galler, JR (1993) Prenatal malnutrition and development of the brain. Neurosci Biobehav Rev 17, 91128.
3Rice, ME (2000) Ascorbate regulation and its neuroprotective role in the brain. Trends Neurosci 23, 209216.
4Rougemont, M, Do, KQ & Castagne, V (2002) New model of glutathione deficit during development: effect on lipid peroxidation in the rat brain. J Neurosci Res 70, 774783.
5Bains, JS & Shaw, CA (1997) Neurodegenerative disorders in humans: the role of glutathione in oxidative stress-mediated neuronal death. Brain Res Brain Res Rev 25, 335358.
6Mahadik, SP & Mukherjee, S (1996) Free radical pathology and antioxidant defense in schizophrenia: a review. Schizophr Res 19, 117.
7Mukerjee, S, Mahadik, SP, Scheffer, R, Correnti, EE & Kelkar, H (1996) Impaired antioxidant defense at the onset of psychosis. Schizophr Res 19, 1926.
8Schulz, JB, Lindenau, J, Seyfried, J & Dichgans, J (2000) Glutathione, oxidative stress and neurodegeneration. Eur J Biochem 267, 49044911.
9Kuo, CH, Yonehara, N & Yoshida, H (1979) Subcellular ascorbic acid in scorbutic guinea pig brain. J Nutr Sci Vitaminol (Tokyo) 25, 913.
10Sotiriou, S, Gispert, S, Cheng, J, et al. (2002) Ascorbic-acid transporter Slc23a1 is essential for vitamin C transport into the brain and for perinatal survival. Nat Med 8, 514517.
11Burk, RF, Christensen, JM, Maguire, MJ, Austin, LM, Whetsell, WO Jr, May, JM, Hill, KE & Ebner, FF (2006) A combined deficiency of vitamins E and C causes severe central nervous system damage in guinea pigs. J Nutr 136, 15761581.
12Hill, KE, Montine, TJ, Motley, AK, Li, X, May, JM & Burk, RF (2003) Combined deficiency of vitamins E and C causes paralysis and death in guinea pigs. Am J Clin Nutr 77, 14841488.
13Madruga de Oliveira, A, de Carvalho Rondo, PH & Barros, SB (2004) Concentrations of ascorbic acid in the plasma of pregnant smokers and nonsmokers and their newborns. Int J Vitam Nutr Res 74, 193198.
14Lykkesfeldt, J (2006) Smoking depletes vitamin C: should smokers be recommended to take supplements? In Cigarette Smoke and Oxidative Stress pp. 237260 [Halliwell, B and Poulsen, HE, editors]. Berlin: Springer Verlag.
15Ratanachu-Ek, S, Sukswai, P, Jeerathanyasakun, Y & Wongtapradit, L (2003) Scurvy in pediatric patients: a review of 28 cases. J Med Assoc Thai 86, Suppl. 3, S734S740.
16Chatterjee, IB (1973) Evolution and the biosynthesis of ascorbic acid. Science 182, 12711272.
17Nandi, A, Mukhopadhyay, CK, Ghosh, MK, Chattopadhyay, DJ & Chatterjee, IB (1997) Evolutionary significance of vitamin C biosynthesis in terrestrial vertebrates. Free Radic Biol Med 22, 10471054.
18Altromin (2007) Altromin Diet 3010 Composition.http://www.altromin.de/content/db.php?nummer = 3010&sprache = de.
19Altromin (2007) Altromin Diet 2010 Composition.http://www.altromin.de/content/db.php?nummer = 2010&sprache = de.
20Lykkesfeldt, J (2000) Determination of ascorbic acid and dehydroascorbic acid in biological samples by high-performance liquid chromatography using subtraction methods: reliable reduction with Tris[2-carboxyethyl]phosphine hydrochloride. Anal Biochem 282, 8993. [Published erratum appears in Anal Biochem (2001) 292, 173.].
21Lykkesfeldt, J (2002) Measurement of ascorbic acid and dehydroascorbic acid in biological samples. In Current Protocols in Toxicology, pp. 7617615 [Maines, M, Costa, LG, Hodson, E and Reed, JC, editors]. New York: John Wiley & Sons.
22Sattler, W, Mohr, D & Stocker, R (1994) Rapid isolation of lipoproteins and assessment of their peroxidation by high-performance liquid chromatography postcolumn chemiluminescence. Meth Enzymol 233, 469489.
23Hissin, PJ & Hilf, R (1976) A fluorometric method for determination of oxidized and reduced glutathione in tissues. Anal Biochem 74, 214226.
24Marklund, S & Marklund, G (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47, 469474.
25Kontush, A & Beisiegel, U (1999) Measurement of oxidizability of blood plasma. Methods Enzymol 299, 3549.
26Lykkesfeldt, J (2001) Determination of malondialdehyde as dithiobarbituric acid adduct in biological samples by HPLC with fluorescence detection: comparison with ultraviolet-visible spectrophotometry. Clin Chem 47, 17251727.
27Buss, IH & Winterbourn, CC (2002) Protein carbonyl measurement by ELISA. Methods Mol Biol 186, 123128.
28Gedik, CM & Collins, A (2005) Establishing the background level of base oxidation in human lymphocyte DNA: results of an interlaboratory validation study. FASEB J 19, 8284.
29Riis, B, Risom, L, Loft, S & Poulsen, HE (2002) OGG1 mRNA expression and incision activity in rats are higher in foetal tissue than in adult liver tissue while 8-oxo-2′-deoxyguanosine levels are unchanged. DNA Repair (Amst) 1, 709717.
30Bradford, MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72, 248254.
31Buettner, GR & Schafer, FQ (2004) Ascorbate as an antioxidant. In Vitamin C: Its Functions and Biochemistry in Animals and Plants, pp. 173188 [Asard, H, May, JM and Smirnoff, N, editors]. Oxford: BIOS Scientific Publishers.
32Rice, ME & Russo-Menna, I (1998) Differential compartmentalization of brain ascorbate and glutathione between neurons and glia. Neuroscience 82, 12131223.
33Hughes, RE, Hurley, RJ & Jones, PR (1971) The retention of ascorbic acid by guinea-pig tissues. Br J Nutr 26, 433438.
34Bercht, M, Flohr-Beckhaus, C, Osterod, M, Runger, TM, Radicella, JP & Epe, B (2007) Is the repair of oxidative DNA base modifications inducible by a preceding DNA damage induction? DNA Repair (Amst) 6, 367373.
35Lykkesfeldt, J (2002) Increased oxidative damage in vitamin C deficiency is accompanied by induction of ascorbic acid recycling capacity in young but not mature guinea pigs. Free Radic Res 36, 567574.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
  • URL: /core/journals/british-journal-of-nutrition
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed