Hostname: page-component-cd9895bd7-7cvxr Total loading time: 0 Render date: 2024-12-29T01:50:39.343Z Has data issue: false hasContentIssue false
  • English
  • Français

Supplementation with α-tocopherol or a combination of α-tocopheroland ascorbic acid protects the gastrointestinal tract of iron-deficientrats against iron-induced oxidative damage during iron repletion

Published online by Cambridge University Press:  09 March 2007

K. Srigiridhar  and
K. Madhavan Nair
K. Srigiridhar
Affiliation:
Department of Biophysics, National Institute of Nutrition, Indian Council of Medical Research, Jamai Osmania (P.O.) Hyderabad 500 007, India
K. Madhavan Nair*
Affiliation:
Department of Biophysics, National Institute of Nutrition, Indian Council of Medical Research, Jamai Osmania (P.O.) Hyderabad 500 007, India
*
*Corresponding author: Dr K. Madhavan Nair, fax +91 40 7019 074, email [email protected]
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.

Recently we have shown the susceptibility of Fe-deficient rat intestine to oxidative damage during Fe repletion. The role of dietary antioxidants like ascorbic acid, α-tocopherol and a combination of both in counteracting the oxidative stress was tested in this study. Five groups of thirteen weanling WKY female rats were fed with an Fe-deficient diet for a period of 5 weeks. Another set of thirteen rats received an Fe-sufficient diet and served as the control group (Con). Oral administration of either vehicle (D), 8 mg Fe alone (D+) or in the presence of 24 mg ascorbic acid (D+ + C), 40 mg α-tocopherol (D+ + E) or a combination of both (D+ + C + E) per d for 15 d was carried out in Fe-depleted rats. The impact of this treatment protocol on Fe status, oxidative stress and antioxidant status at the site of Fe absorption was assessed. It was observed that though the indicators of Fe status were normalised on Fe supplementation, the oxidative stress as reflected by the levels of both thiobarbituric-acid reactive substances (TBARS) and protein carbonyls were significantly greater in D+ and D+ + C compared to D+ + E, D+ + C + E and Con groups. The mucosal cell DNA damage was seen in D+, D+ + C and D+ + E groups on electrophoresis. Functional integrity as assessed by the activities of alkaline phosphatase and lys-ala-dipeptidyl aminopeptidase were normalized in all the groups treated with the antioxidant(s). There were significant positive alterations in some of the endogenous antiperoxidative systems and in serum caeruloplasmin activity in D+ + E and D+ + C + E groups. Paradoxically, serum ascorbate levels were significantly lower in D+ + C than in D+ + E and D+ + C + E groups. This could be due to the protection offered by α-tocopherol in the presence of Fe. It is concluded that supplementation of α-tocopherol alone or in combination with ascorbic acid protects the gastrointestinal tract of Fe-deficient rats against Fe-mediated oxidative damage during Fe repletion. However, ascorbic acid alone does not protect the gastrointestinal tract against Fe-induced oxidative stress.

Keywords

IronOxidative stressAscorbic acid-Tocopherol
Type
Research Article
Information
British Journal of Nutrition , Volume 84 , Issue 2 , August 2000 , pp. 165 - 173
Copyright
Copyright © The Nutrition Society 2000

References

Aebi, HE (1983) Catalase. In Methods in Enzymatic Analysis, vol. III, pp. 273–282 ]Bergmeyer, HU, editor] Weinhein, Germany: Verlog Chemie.Google Scholar
Almaas, R, Rootwell, T, Oyasaeter, S and Saugstad, OD (1997) Ascorbic acid enhances hydroxyl radical formation in iron-fortified infant cereals and infant formulas. European Journal of Pediatrics 156, 488–492.CrossRefGoogle ScholarPubMed
Balasubramanian, KA, Manohar, M and Mathan, VI (1988) An unidentified inhibitor of lipid peroxidation in intestinal mucosa. Biochimica et Biophysica Acta 962, 51–58.CrossRefGoogle ScholarPubMed
Bodansky, A (1932) Determination of inorganic phosphate. Beers law and interfering substances in the Kuttner Lichten Stein method. Journal of Biological Chemistry 99, 197–206.CrossRefGoogle Scholar
Bradford, MM (1976) A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry 72, 248–254.CrossRefGoogle Scholar
Chen, PS, Toribara, TY and Warner, H (1956) Estimation of phosphorus in serum by colorimetric method. Analytical Chemistry 28, 1756–1777.CrossRefGoogle Scholar
Cook, JD and Monsen, ER (1977) Vitamin C, the common cold and iron absorption. American Journal of Clinical Nutrition 53, 106–111.CrossRefGoogle Scholar
Eloy, R, Haffen, K & Hrenier, JF (1978) Enzymes in the normal and diseased small intestinal mucosa: Development, localization, secretion and control. In Progress in Gastroenterology, vol. III, pp. 439–479 ]Glass, GBJ, editor] New York, NY: Grune and Stratton.Google Scholar
Gutteridge, JMC and Quinlan, GJ (1993) Antioxidant protection against organic and inorganic oxygen radicals by normal human plasma: The important primary role for iron-binding and iron-oxidising proteins. Biochimica et Biophysica Acta 1156, 144–150.CrossRefGoogle ScholarPubMed
Halliwell, B (1996) Antioxidants in human health and disease. In Annual Review of Nutrition, vol. 16, pp. 33–50 ]McCormick, DB, Bier, DM and Goodridge, AG, editors]. Palo Alto, CA: Annual Reviews Inc.Google Scholar
Halliwell, B & Gutteridge, JMC (1979) Free Radicals in Biology and Medicine, 2nd ed. Oxford: Clavendon Press.Google Scholar
Halliwell, B and Gutteridge, JMC (1986) Oxygen free radicals and iron in relation to biology and medicine: some problems and concepts. Archives of Biochemistry and Biophysics 246, 501–514.CrossRefGoogle ScholarPubMed
Herbert, V, Shaw, S and Jayatilleke, E (1996) Vitamin C driven free radical generation from iron. Journal of Nutrition 126, 12138–12205.CrossRefGoogle ScholarPubMed
Horn, E (1988) Iron and folate supplements during pregnancy: Supplementing everyone treats those at risk and is cost effective. British Medical Journal 297, 1325–1327.CrossRefGoogle ScholarPubMed
Horwitt, MK (1991) Data supporting supplementation of humans with vitamin E. Journal of Nutrition 121, 424–429.CrossRefGoogle ScholarPubMed
Indian Council of Medical Research Task Force Study (1989) Evaluation of the National Nutritional Anaemia Prophylaxis Programme. New Delhi: Indian Council of Medical Research.Google Scholar
Indian Council Task Force Study (1992) Field Supplementation Trial in Pregnant Women with 60 mg, 120 mg and 180 mg of Iron with 500 μg Folic Acid. New Delhi: Indian Council of Medical Research.Google Scholar
International Committee for Standardization in Haematology (ICSH) (1971), Proposed recommendations for measurement of serum iron in human blood. British Journal of Haematology 20, 451–454.CrossRefGoogle Scholar
Imai, K, Hama, T and Kato, T (1983) Purification and properties of brain dipeptidyl aminopeptidase. Journal of Biochemistry 93, 431–437.CrossRefGoogle ScholarPubMed
Johnson, DA, Osaki, S and Frieden, E (1967) A macro method for the determination of ferroxidase (ceruloplasmin) in human serum. Clinical Chemistry 13, 143–150.CrossRefGoogle Scholar
Kadiiska, MB, Murkitt, MJ, Xiang, QH and Mason, RP (1995) Iron supplementation generates hydroxyl radical. in vivo. An ESR spin-trapping investigation. Journal of Clinical Investigation 96, 1653–1657.CrossRefGoogle ScholarPubMed
Kimmich, GA (1970) Preparation and properties of mucosal epithelial cells isolated from small intestine of the chicken. Biochemistry 9, 3659–3668.CrossRefGoogle ScholarPubMed
Krsek-Staples, JA and Webster, RO (1993) Ceruloplasmin inhibits carbonyl formation in endogenous cell proteins. Free Radical Biology and Medicine 14, 115–125.CrossRefGoogle ScholarPubMed
McCord, JM (1998) Iron, free radicals and oxidative injury. Seminars in Haematology 35, 5–12.Google ScholarPubMed
McGowan, AJ, Fernandes, RS, Verhaegen, S and Cotter, TG (1994) Zinc inhibits UV radiation induced apoptosis but fails to prevent subsequent cell death. International Journal of Radiation Biology 66, 343–349.CrossRefGoogle ScholarPubMed
Machlin, LJ and Bendich, A (1987) Free radical tissue damage: Protective role of antioxidant nutrients. FASEB Journal 1, 441–445.CrossRefGoogle ScholarPubMed
Marklund, S and Marklund, G (1974) Involvement of the superoxide anion radical in the auto-oxidation of pyrogallol and a convenient assay for superoxide dismutase. European Journal of Biochemistry 47, 469–474.CrossRefGoogle Scholar
Miller, KW, Lorr, NA and Yang, CS (1984) Simultaneous determination of plasma retinol, α-tocopherol, lycopene, α-carotene, and β-carotene by high performance liquid chromatography. Analytical Biochemistry 138, 340–345.CrossRefGoogle ScholarPubMed
Mukhopadhyay, CK, Atteih, ZK and Fox Pl (1998) Role of ceruloplasmin in cellular iron uptake. Science 279, 714–717.CrossRefGoogle ScholarPubMed
Omara, FO and Blakley, BR (1993) Vitamin E is protective against iron toxicity and iron induced hepatic vitamin E depletion in mice. Journal of Nutrition 123, 1649–1655.CrossRefGoogle ScholarPubMed
Packer, L and Landvick, S (1989) Vitamin E: Introduction to biochemistry and health benefits. Annals of New York Academy of Sciences 570, 1–6.CrossRefGoogle ScholarPubMed
Paglia, DE and Valentine, WN (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. Journal of Laboratory and Clinical Medicine 70, 158–169.Google ScholarPubMed
Podmore, ID, Griffiths, HR, Herbert, KE, Mistry, N, Mistry, P and Lunec,, J (1998) Vitamin C exhibits pro-oxidant properties. Nature 392, 559.CrossRefGoogle ScholarPubMed
Rachmilewitz, EA, Lubin, BH and Shohet, SB (1976) Lipid membrane peroxidation in β-thalassaemia major. Blood 47, 495–505.CrossRefGoogle Scholar
Rayan, TP and Aust, SD (1992) The role of iron in oxygen mediated toxicity. Critical Reviews in Toxicology 22, 119–141.CrossRefGoogle Scholar
Reznick, AZ & Packer, L (1993) Oxidative damage to proteins: A spectrophotometric method for carbonyl assay. In Methods in Enzymology. Oxygen Radicals in Biological Systems, part C, vol. 233, 357–363.CrossRefGoogle Scholar
Roxborough, HE, Miller, CA, McEney, T and Young, IS (1995) Carbamylation inhibits the ferroxidase activity of ceruloplasmin. Biochemical and Biophysical Research Communications 214, 1073–1078.CrossRefGoogle Scholar
Slivka, A, Kang, J and Cohen, G (1986) Hydroxyl radicals and the toxicity of oral iron. Biochemical Pharmacology 35, 553–556.CrossRefGoogle ScholarPubMed
Srigiridhar, K and Nair, KM (1998) Iron deficient intestine is more susceptible to peroxidative damage during iron supplementation in rats. Free Radical Biology and Medicine 25, 660–665.CrossRefGoogle ScholarPubMed
Wienk, KJH, Marx, J JM, Santos, M, Lemmens, AG, Brink, EJ, Meer Vander Meer, R and & Beynen, AC (1997) Dietary ascorbic acid raises iron absorption in anaemic rats through enhancing mucosal iron uptake independent of iron solubility in the digesta. British Journal of Nutrition 77, 123–131.CrossRefGoogle ScholarPubMed
Yu, S, West, CE and Beynen, AC (1993) Increasing intakes of iron reduce status, absorption and biliary excretion of copper in rats. British Journal of Nutrition 71, 887–895.CrossRefGoogle Scholar
Zannoni, VM, Lynch, M, Goldstein, S and Sato, P (1974) A rapid micro method for the determination of ascorbic acid in plasma and tissues. Biochemical Medicine 11, 41–48.CrossRefGoogle Scholar