Hostname: page-component-848d4c4894-75dct Total loading time: 0 Render date: 2024-06-11T19:47:17.594Z Has data issue: false hasContentIssue false
  • English
  • Français

Iron loading and large doses of intravenous ascorbic acid promote lipid peroxidation in whole serum in guinea pigs

Published online by Cambridge University Press:  09 March 2007

Maria Kapsokefalou  and
Dennis D Miller
Maria Kapsokefalou*
Affiliation:
Cornell Institute of Food Science, Stocking Hall, Cornell University, Ithaca, NY 14853-7201, USA
*
*Corresponding author: Dr Maria Kapsokefalou, present address Department of Chemistry, University of Crete, Heraklion, POB 1470, Greece, fax + 3081 210951, email kapsok@athina.cc.uch.gr
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Large doses of ascorbic acid may mobilise Fe from Fe-binding proteins in vivo which in turn could catalyse lipid peroxidation, a process associated with degenerative diseases. This hypothesis was tested in vitro in the serum of Fe-loaded animals. Eighteen male guinea pigs weighing about 500 g on arrival were allocated to two groups of nine. Fe loading was induced in one group by two intraperitoneal injections of 200 mg iron dextran given on days 1 and 5. Blood (6 ml) was drawn from all animals on day 12 by cardiac puncture. Serum and LDL were separated. Serum was tested for loosely-bound Fe (bleomycin assay) and lipid peroxidation (thiobarbituric acid reactive substances (TBARS) assay) and LDL for susceptibility to in vitro oxidation (TBARS and conjugated diene assays). On day 12, another intraperitoneal injection of 200 mg iron dextran was given to the animals in the Fe-loaded group. On day 19, all animals were given 75 mg ascorbic acid by intraperitoneal injection. Blood (6 ml) was drawn 4 h later by cardiac puncture. Serum and LDL assays were repeated. Ascorbic acid increased loosely-bound Fe and in vitro oxidation in the serum from animals of the Fe-loaded group but not in the serum from animals of the control group. Susceptibility of LDL to in vitro oxidation increased after the ascorbic acid injection in the control group but there was no further increase in the Fe-loaded group. These data suggest that large doses of ascorbic acid promote Fe mobilisation and in vitro oxidation in the serum of Fe-loaded animals.

Keywords

IronAscorbic acidOxidation
Type
Research Article
Information
British Journal of Nutrition , Volume 85 , Issue 6 , May 2001 , pp. 681 - 687
Copyright
Copyright © The Nutrition Society 2001

References

Ascherio, A, Willet, WC, Rimm, EB, Giovannucci, EL & Stampfer, MJ (1994) Dietary iron intake and risk of coronary disease among men. Circulation 89, 969–974.Google Scholar
Aust, SD (1987) Sources of iron for lipid peroxidation in biological systems.In Oxygen radicals and tissue injury 27–33.[Halliwell, B, editor]. Bethesda, MD: Upjohn Co, by the FASEB.Google Scholar
Casalino, E, Sblano, C & Landriscina, C (1996) A possible mechanism for initiation of lipid peroxidation by ascorbate in rat liver microsomes. International Journal of Biochemistry and Cell Biology 28, 137–149.CrossRefGoogle ScholarPubMed
Chen, LH & Chang, HM (1978) Effects of high level of vitamin C on tissue oxidant status of guinea pigs. International Journal of Vitamin and Nutritional Research 49, 87–91.Google Scholar
Corti, MC, Guralnik, JM, Salive, ME, Ferrucci, L, Pahor, M, Wallace, RB & Hennekens, CH (1997) Serum iron level, coronary artery disease, and all-cause mortality in older men and women. American Journal of Cardiology 79, 120–127.CrossRefGoogle ScholarPubMed
Dasgupta, A & Zdunek, T (1992) In vitro lipid peroxidation of human serum catalyzed by cupric ion: Antioxidant rather than prooxidant role of ascorbate. Life Sciences 50, 875–882.CrossRefGoogle ScholarPubMed
Dillard, JC, Downey, JE & Tappel, AL (1984) Effect of antioxidants on lipid peroxidation in iron-loaded guinea pigs. Lipids 19, 127–133.CrossRefGoogle Scholar
Esterbauer, H, Gebiki, J, Puhl, H & Jurgens, G (1992) The role of lipid peroxidation and antioxidants in oxidative modification of LDL. Free Radicals in Biology and Medicine 13, 341–390.CrossRefGoogle ScholarPubMed
Frei, B, England, L & Ames, BN (1989) Ascorbate is an outstanding antioxidant in human blood plasma. Proceedings of the National Academy of Sciences 86, 6377–6381.CrossRefGoogle ScholarPubMed
Goldberg, L & Martin, LE (1960) Iron overloading phenomena in animals. Toxicology and Applied Pharmacology 2, 683–707.Google Scholar
Gutteridge, JM, Halliwell, B, Treffry, A, Harrision, PM & Blake, D (1983) Effect of ferritin-containing fractions with different iron loading on lipid peroxidation. Biochemical Journal 209, 557–560.CrossRefGoogle ScholarPubMed
Gutteridge, JM & Hou, Y (1986) Iron complexes and their reactivity in the bleomycin assay for radical-promoting loosely-bound iron. Free Radical Research Communications 2, 143–151.Google Scholar
Gutteridge, JM & Halliwell, B (1987) Radical promoting loosely bound iron in biological fluids and the bleomycin assay. Life Chemistry Reports 4, 113–142.Google Scholar
Gutteridge, JM (1987) Lipid peroxidation: Some problems and concepts. In Oxygen Radicals and Tissue Injury, pp. 9–19 [Halliwell, B, editor]. Bethesda, MD: Upjohn Co, by the FASEB.Google Scholar
Halliwell, B & Chirico, S (1993) Lipid peroxidation: its mechanism, measurement, and significance. American Journal of Clinical Nutrition 57, 715S–725S.CrossRefGoogle ScholarPubMed
Herbert, V (1983) Viewpoint. Does mega-C do more good than harm, or more harm than good?. Nutrition Today 1, 28–32.Google Scholar
Kanner, J, Sofer, F, Harell, S & Doll, L (1988) Antioxidant activity of ceruloplasmin in muscle membrane and in situ lipid peroxidation. Journal of Agricultural and Food Chemistry 36, 415–417.CrossRefGoogle Scholar
Kunert, KJ & Tappel, AL (1983) The effect of vitamin C on. in vivo lipid peroxidation in guinea pigs as measured by pentane and ethane production Lipids 18, 271–274.Google Scholar
Liao, Y, Cooper, RS & McGee, DL (1994) Iron status and coronary heart disease: Negative findings from the NHANES I epidemiologic follow-up study. American Journal of Epidemiology 139, 704–712.CrossRefGoogle ScholarPubMed
Miller, JC & Miller, JN (1993) Errors in instrumental analysis; regression and correlation. In Statistics for Analytical Chemistry,3rd ed.: Ellis Horwood Limited: Chichester, UK.Google Scholar
Minotti, G & Aust, S (1992) Redox cycling of iron and lipid peroxidation. Lipids 27, 219–226.Google Scholar
O'Connel, MJ, Ward, RJ, Baum, H & Peters, TJ (1985) The role of iron in ferritin- and haemosiderin-mediated lipid peroxidation in liposomes. Biochemical Journal 229, 135–139.CrossRefGoogle Scholar
Parthasarathy, S, Khoo, JC, Miller, E, Barnett, J, Witztum, JL & Steinberg, D (1990) Low density lipoprotein rich in oleic acid is protected against oxidative modification: Implications for dietary prevention of atherosclerosis. Proceedings of the National Academy of Sciences 87, 3894–3898.CrossRefGoogle Scholar
Poole, T (1987) The guinea pig. In The UFAW Handbook on the Care and Management of Laboratory Animals 6th ed.:393–410.[T, Poole, editor]. London: Longman Scientific & Technical.Google Scholar
Reaven, P, Parthasarathy, S, Grasse, BJ, Miller, E, Almazan, F, Mattson, FH, Khoo, JC, Steinberg, D & Witztum, JL (1991) Feasibility of using an oleate-rich diet to reduce the susceptibility of low-density lipoprotein to oxidative modification in humans. American Journal of Clinical Nutrition 54, 701–706.CrossRefGoogle ScholarPubMed
Reunanen, A, Takkunen, H, Knekt, P, Seppanen, R & Aroma, A (1995) Body iron stores, dietary iron intake and coronary heart disease mortality. Journal of Internal Medicine 238, 223–230.Google Scholar
Rifici, VA & Khachadurian, AK (1993) Dietary supplementation with vitamins C and E inhibits. in vitro oxidation of lipoproteins Journal of the American College of Nutrition 12, 631–637.Google Scholar
Salonen, JT, Nyssonen, K, Korpela, H, Toumilethto, J, Sepanen, R & Salonen, R (1992) High stored iron levels are associated with excess risk of myocardial infarction in Eastern Finnish men. Circulation 86, 803–811.CrossRefGoogle ScholarPubMed
Simpson, RJ, Cooper, CE, Raja, KB, Halliwell, B, Evans, PJ, Aruoma, OI, Singh, S & Konijn, AM (1992) Non-transferrin-bound iron species in the serum of hypotransferrinaemic mice. Biochimica et Biophysica Acta 1156, 19–26.CrossRefGoogle ScholarPubMed
Snedecor, GW & Cochran, WG (1980) Shortcut and nonparametric methods. In Statistical Methods 135–148. Ames,IA: The Iowa State University Press.Google Scholar
Steinberg, D, Parthasarathy, S, Carew, T, Khoo, JC & Witztum, JL (1989) Beyond cholesterol: Modifications of low density lipoprotein that increase its atherogenicity. New England Journal of Medicine 320, 915–924.Google ScholarPubMed
Steinbrecher, PU, Parthasarathy, S, Leake, SD, Witztum, LJ & Steinberg, D (1984) Modification of low density lipoprotein by endothelial cells involves lipid peroxidation and degradation of low density lipoprotein phospholipids. Proceedings of the National Academy of Sciences 81, 3883–3887.Google Scholar
Sullivan, JL (1989) The iron paradigm of ischemic heart disease. American Heart Journal 117, 1177–1188.Google Scholar
Tuomainen, TP, Punnonen, K, Nyyssonen, K & Salonen, JT (1998) Association between body iron stores and the risk of acute myocardial infarction in men. Circulation 97, 1461–1466.Google Scholar
Tzonou, A, Lagiou, P, Trichopoulou, A, Tsoutsos, V & Trichopoulos, D (1998) Dietary iron and coronary heart disease risk: a study from Greece. American Journal of Epidemiology 147, 161–166.CrossRefGoogle Scholar
Yamamoto, K & Niki, E (1988) Interaction of α-tocopherol with iron: antioxidant and prooxidant effects of α-tocopherol in the oxidation of lipids in aqueous dispersions in the presence or iron. Biochimica et Biophysica Acta 958, 19–23.CrossRefGoogle ScholarPubMed