DOI QR코드

DOI QR Code

Long-Term Intake of High Doses of Vitamin C Down-regulates Anti-oxidant Enzymes in Human Erythrocytes

  • Kim, Hee-Joon (Department of Pharmacology, Dankook University College of Medicine) ;
  • Park, Min-Kyung (Department of Human Nutrition and Food Science, Chungwoon University) ;
  • Rhee, Kwang-Ho (Department of Microbiology, Gyeongsang University College of Medicine) ;
  • Youn, Hee-Sang (Department of Pediatrics, Gyeongsang University College of Medicine) ;
  • Ko, Seong-Hee (Food and Nutrition, College of Human Ecology, Sookmyung Women's University) ;
  • Kim, Hyun-Sook (Food and Nutrition, College of Human Ecology, Sookmyung Women's University) ;
  • Chung, Myung-Hee (Department of Pharmacology, Seoul National University School of Medicine)
  • Published : 2008.09.30

Abstract

We located a group of healthy young males (aged $20{\sim}30$) who had been taking a high dose (more than 5 g) of vitamin C daily for more than one year. We observed that this vitamin C group had plasma levels of vitamin C that were more than three times that of the control group. The control group had not taken any additional vitamin C except for that included in their diets. But the vitamin C group showed significantly lower amounts of Cu/ZnSOD, catalase and glutathione-s-transferase and lower activities of glutathione peroxidase and glutathione reductase in erythrocyte lysates than the control group. However, there was no difference in the plasma levels of lipid peroxides between the two groups. These results suggest that vitamin C offsets its own contribution to anti-oxidant activity by repressing the expression of anti-oxidant enzymes and also excludes the possibility that vitamin C acts as a pro-oxidant in vivo.

Keywords

References

  1. Li QT, Yeo MH, Tan BK. 2000. Lipid peroxidation in small and large phospholipid unilamellar vesicles induced by water-soluble free radical sources. Biochem Biophys Res Commun 273: 72-76 https://doi.org/10.1006/bbrc.2000.2908
  2. Du J, Gebicki JM. 2004. Proteins are major initial cell targets of hydroxyl free radicals. Int J Biochem Cell Biol 36: 2334-2343 https://doi.org/10.1016/j.biocel.2004.05.012
  3. Patrzyc HB, Dawidzik JB, Budzinski EE, Iijima H, Box HC. 2001. Double lesions are produced in DNA oligomer by ionizing radiation and by metal-catalyzed $H_2O_2$ reactions. Radiat Res 155: 634-636 https://doi.org/10.1667/0033-7587(2001)155[0634:DLAPID]2.0.CO;2
  4. Mates JM, Sanchez-Jimenez F. 1999. Antioxidant enzymes and their implications in pathophysiologic processes. Front Biosci 4: D339-345 https://doi.org/10.2741/Mates
  5. Chaudiere J, Ferrari-Iliou R. 1999. Intracellular antioxidants: from chemical to biochemical mechanisms. Food Chem Toxicol 37: 949-962 https://doi.org/10.1016/S0278-6915(99)00090-3
  6. Tao F, Gonzalez-Flecha B, Kobzik L. 2003. Reactive oxygen species in pulmonary inflammation by ambient particulates. Free Radic Biol Med 35: 327-340 https://doi.org/10.1016/S0891-5849(03)00280-6
  7. Yamagishi S, Ueda S, Matsui T, Nakamura K, Okuda S. 2008. Role of advanced glycation end products (AGEs) and oxidative stress in diabetic retinopathy. Curr Pharm Des 14: 962-968 https://doi.org/10.2174/138161208784139729
  8. Sasaki M, Joh T. 2007. Oxidative stress and ischemia-reperfusion injury in gastrointestinal tract and antioxidant, protective agents. J Clin Biochem Nutr 40: 1-12 https://doi.org/10.3164/jcbn.40.1
  9. Jablonski KL, Seals DR, Eskurza I, Monahan KD, Donato AJ. 2007. High-dose ascorbic acid infusion abolishes chronic vasoconstriction and restores resting leg blood flow in healthy older men. J Appl Physiol 103: 1715-1721 https://doi.org/10.1152/japplphysiol.00533.2007
  10. Lee CW, Wang XD, Chien KL, Ge Z, Rickman BH, Rogers AB, Varro A, Whary MT, Wang TC, Fox JG. 2008. Vitamin C supplementation does not protect L-gulono-gamma-lactone oxidase-deficient mice from Helicobacter pylori-induced gastritis and gastric premalignancy. Int J Cancer 122: 1068-1076 https://doi.org/10.1002/ijc.23228
  11. Reynolds M, Stoddard L, Bespalov I, Zhitkovich A. 2007. Ascorbate acts as a highly potent inducer of chromate mutagenesis and clastogenesis: linkage to DNA breaks in $G_2$ phase by mismatch repair. Nucleic Acids Res 35: 465-476 https://doi.org/10.1093/nar/gkl1069
  12. Winterbourn CC, Benatti U, De Flora A. 1986. Contributions of superoxide, hydrogen peroxide, and transition metal ions to auto-oxidation of the favism-inducing pyrimidine aglycone, divicine, and its reactions with haemoglobin. Biochem Pharmacol 35: 2009-2015 https://doi.org/10.1016/0006-2952(86)90734-3
  13. Towbin H, Staehelin T, Gordon J. 1979. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci USA 76: 4350-4354 https://doi.org/10.1073/pnas.76.9.4350
  14. Gunzler WA, Kremers H, Flohe L. 1974. An improved coupled test procedure for glutathione peroxidase (EC 1-11-1-9-) in blood. Z Klin Chem Klin Biochem 12: 444-448
  15. Carlberg I, Mannervik B. 1985. Glutathione reductase. Methods Enzymol 113: 484-490 https://doi.org/10.1016/S0076-6879(85)13062-4
  16. Hughes RE. 1956. The use of homocysteine in the estimation of dehydroascorbic acid. Biochem J 64: 203-208 https://doi.org/10.1042/bj0640203
  17. Yagi H, Horinaka S, Matsuoka H. 2005. Edaravone prevented deteriorated cardiac function after myocardial ischemia-reperfusion via inhibiting lipid peroxidation in rat. J Cardiovasc Pharmacol 46: 46-51 https://doi.org/10.1097/01.fjc.0000162772.16797.7f
  18. Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzano MD, Fujimoto EK, Goeke NM, Olson BJ, Klenk DC. 1985. Measurement of protein using bicinchoninic acid. Anal Biochem 150: 76-85 https://doi.org/10.1016/0003-2697(85)90442-7
  19. Dehghan M, Akhtar-Danesh N, McMillan CR, Thabane L. 2007. Is plasma vitamin C an appropriate biomarker of vitamin C intake? A systematic review and metaanalysis. Nutr J 6: 41-52 https://doi.org/10.1186/1475-2891-6-41
  20. Purdom-Dickinson SE, Sheveleva EV, Sun H, Chen QM. 2007. Translational control of Nrf2 protein in activation of antioxidant response by oxidants. Mol Pharmacol 72: 1074-1081 https://doi.org/10.1124/mol.107.035360
  21. Iqbal J, Clerch LB, Hass MA, Frank L, Massaro D. 1989. Endotoxin increases lung Cu,Zn superoxide dismutase mRNA: O2 raises enzyme synthesis. Am J Physiol 257: L61-64
  22. Niwa Y, Ishimoto K, Kanoh T. 1990. Induction of superoxide dismutase in leukocytes by paraquat: correlation with age and possible predictor of longevity. Blood 76: 835-841
  23. Kong XJ, Fanburg BL. 1992. Regulation of Cu,Zn-superoxide dismutase in bovine pulmonary artery endothelial cells. J Cell Physiol 153: 491-497 https://doi.org/10.1002/jcp.1041530308
  24. Alvarez A, Boveris A. 1993. Induction of antioxidant enzymes and DT-diaphorase in human blood mononuclear cells by light stress. Arch Biochem Biophys 305: 247-251 https://doi.org/10.1006/abbi.1993.1418
  25. Tarumoto T, Nagai T, Ohmine K, Miyoshi T, Nakamura M, Kondo T, Mitsugi K, Nakano S, Muroi K, Komatsu N, Ozawa K. 2004. Ascorbic acid restores sensitivity to imatinib via suppression of Nrf2-dependent gene expression in the imatinib-resistant cell line. Exp Hematol 32: 375-381 https://doi.org/10.1016/j.exphem.2004.01.007
  26. Gomez-Cabrera MC, Domenech E, Romagnoli M, Arduini A, Borras C, Pallardo FV, Sastre J, Vina J. 2008. Oral administration of vitamin C decreases muscle mitochondrial biogenesis and hampers training-induced adaptations in endurance performance. Am J Clin Nutr 87: 142-149 https://doi.org/10.1093/ajcn/87.1.142
  27. Ross MH, kaye GI, Pawline W. 2003. Histology; a text and atlas. 4th ed. Lippincott Williams & Wilkins, Baltimore. p 236-237
  28. Rabadi MH, Kristal BS. 2007. Effect of vitamin C supplementation on stroke recovery: a case-control study. Clin Interv Aging 2: 147-151 https://doi.org/10.2147/ciia.2007.2.1.147
  29. Slatore CG, Littman AJ, Au DH, Satia JA, White E. 2008. Long-term use of supplemental multivitamins, vitamin C, vitamin E, and folate does not reduce the risk of lung cancer. Am J Respir Crit Care Med 177: 524-530 https://doi.org/10.1164/rccm.200709-1398OC
  30. Lee CW, Wang XD, Chien KL, Ge Z, Rickman BH, Rogers AB, Varro A, Whary MT, Wang TC, Fox JG. 2008. Vitamin C supplementation does not protect L-gulono-gamma-lactone oxidase-deficient mice from Helicobacter pylori-induced gastritis and gastric premalignancy. Int J Cancer 122: 1068-1076 https://doi.org/10.1002/ijc.23228
  31. Canter PH, Wider B, Ernst E. 2007. The antioxidant vitamins A, C, E and selenium in the treatment of arthritis: a systematic review of randomized clinical trials. Rheumatology (Oxford) 46: 1223-1233 https://doi.org/10.1093/rheumatology/kem116
  32. Santos LF, Freitas RL, Xavier SM, Saldanha GB, Freitas RM. 2008. Neuroprotective actions of vitamin C related to decreased lipid peroxidation and increased catalase activity in adult rats after pilocarpine-induced seizures. Pharmacol Biochem Behav 89: 1-5 https://doi.org/10.1016/j.pbb.2007.10.007
  33. Acharya UR, Mishra M, Patro J, Panda MK. 2008. Effect of vitamins C and E on spermatogenesis in mice exposed to cadmium. Reprod Toxicol 25: 84-88 https://doi.org/10.1016/j.reprotox.2007.10.004
  34. Friel JK, Diehl-Jones WL, Suh M, Tsopmo A, Shirwadkar VP. 2007. Impact of iron and vitamin C-containing supplements on preterm human milk: in vitro. Free Radic Biol Med 42: 1591-1598 https://doi.org/10.1016/j.freeradbiomed.2007.02.022
  35. Reynolds M, Stoddard L, Bespalov I, Zhitkovich A. 2007. Ascorbate acts as a highly potent inducer of chromate mutagenesis and clastogenesis: linkage to DNA breaks in G2 phase by mismatch repair. Nucleic Acids Res 35: 465-476 https://doi.org/10.1093/nar/gkl1069
  36. Duarte TL, Jones GD. 2007. Vitamin C modulation of $H_2O_2$-induced damage and iron homeostasis in human cells. Free Radic Biol Med 43: 1165-1175 https://doi.org/10.1016/j.freeradbiomed.2007.07.017