Abstract
Free radical mediated effects on the gastrointestinal (GI) tract were studied by supplementing 8 mg of iron orally for 15 days to groups of both control (C+) and iron deficient (D+) rats. They were compared with their respective unsupplemented groups C and D. Incorporation of 3H-thymidine into the isolated mucosal cells, as a measure of cell turn over, was lowered significantly in both the D+ and C+ groups compared to their respective controls D and C. It was observed that a single dose of 8 mg of iron given orally to control rats could cause apoptosis of GI tract mucosal cells as shown by the ladder pattern of DNA on electrophoresis. Continuous administration of the same dose of iron for a period of 15 days resulted in necrosis of the GI tract absorptive surface in D+ and C+ rats. In addition to this, a reduction of microvillus height in C+ and complete erosion of the same in D+ were observed by the transmission electron microscopy. EPR spectroscopy identified production of hydroxyl and methoxyl radicals in both the luminal and mucosal contents in the GI tract of rats. These results suggest that when iron is orally administered, free radicals are formed at the site of absorption causing damage to the GI tract mucosa.
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References
Freeman BA, Crapo ID: Biology of disease: Free radicals and tissue injury. Lab Invest 47: 412–426, 1982
Yip R: Iron deficiency: Contemporary scientific issues and international programmatic approaches. J Nutr 124(suppl): 1479S–1490S, 1993
Vijayaraghavan K, Brahmam GNV, Nair KM, Akbar D, Pralhad Rao N: Evaluation of nutritional anemia prophylactic programme. Indian J Pediatr 57: 183–190, 1990
De Maeyer EM, Dallman P, Gurney JM, Hallberg L, Sood SK, Srikantia SG: Preventing and controlling iron deficiency anaemia through primary health care: A guide for health administers and programme managers. World Health Organisation Geneva, 1989
Ridwan E, Schultink W, Dillon D, Gross R: Effects of weekly iron supplementation on pregnant Indonesian women are similar to those of daily supplementation. Am J Clin Nutr 63: 884–890, 1996
Fairweather-Tait SJ, Wright AJ: The influence of previous iron intake on the estimation of bioavailability of Fe from a test meal given to rats. Br J Nutr 51: 185–191, 1984
Srigiridhar K, Nair KM: Protective effects of antioxidant enzymes and GSH in vivo on iron mediated lipid peroxidation in gastrointestinal tract of rat. Indian J Biophys Biochem 34: 402–405, 1997
Srigiridhar K, Nair KM: Iron deficient intestine is more susceptible to peroxidative damage during iron supplementation in rats. Free Radic Biol Med 25: 660–665, 1998
Reeves PG, Niessen HF, Fahey RJCG: AIN-93 purified diets for laboratory rodents: Final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr 123: 1939–1951, 1993
Kimmich GA: Preparation and properties of mucosal epithelial cells isolated from small intestine of the chicken. Biochemistry 9: 3659–3668, 1970
Nichols BL, McKee KS, Henry JF, Putman M: Human lactoferrin stimulates thymidine incorporation into DNA of rat crypt cells. Pediatr Res 21: 563–567, 1987
Lanford RE, Butel JS: Effect of nuclear localisation of large tumour antigen on growth potential of SV40-transformed cells. Virology 110: 147–158, 1981
Jean-Bernard LP, Paoletti C: A new fluorometric method for RNA and DNA determination. Anal Biochem 17: 100–107, 1996
McGowan AJ, Fernandes RS, Verhaegen S, Cotter TG: Zinc inhibits UV radiation-induced apoptosis but fails to prevent subsequent cell death. Int J Rad Biol 66: 343–349, 1994
Duling DR: Simulation of multiple isotropic spin-trap EPR spectra. J Mag Resonance Series B 104: 105–110, 1994
Karnovsky M J: A formaldehyde-glutaraldehyde fixative of high osmolality for use in electron microscopy. J Cell Biol 27: 137A–138A, 1965
Gerschenson LE, Rotello RJ: Apoptosis: A different type of cell death: FASEB J 6: 2450–2455, 1992
Aruoma OI, Halliwell B, Gajewski E, Dizdaroglu M: Damage to the bases in DNA induced by hydrogen peroxide and ferric ion chelates. J Biol Chem 264: 20508–20512, 1989
Holt PR, Kotler DP, Pascal RR: A simple method for determining epithelial cell turnover in small intestine. Gastroenterology 84: 69–74, 1983
Fairweather-Tait SJ, Swindell TS, Wright AJA: Further studies in rats on the influence of iron intake on the estimation of bioavailability of Fe. Br J Nutr 54: 79–86, 1985
Liu X-N, Kang LJ, Zhao L, Viteri FE: Intermittent iron supplementation in Chinese pre-school children is efficient and safe. Food Nutr Bull 16: 139–146, 1995
Charoenlarp P, Dhanamitta S, Kaewvichit RA, Silprasert A, Suwanaradd C, Na-Nakorn S, Prawatmuang P, Vatanavicharn S, Nutcharas U, Pootrakul P: A WHO collaborative study on iron supplementation in Burma and in Thailand. Am J Clin Nutr 47: 280–297, 1988
Bacon BR, Britton RS: The pathology of hepatic iron overload: A free radical mediated process? Hepatology 11: 127–137, 1990
Burkitt MJ, Mason RP: Direct evidence for in vivo hydroxyl-radical generation in experimental iron overload: An ESR spin-trapping investigation. Proc Natl Acad Sci (USA) 88: 8440–8444, 1991
Srigiridhar K, Nair KM: Supplementation with α-tocopherol or a combination of α-tocopherol and ascorbic acid protects the gastrointestinal tract of iron deficient rats against iron induced oxidative damage during iron repletion. Br J Nutr 84: 165–173, 2000
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Srigiridhar, K., Madhavan Nair, K., Subramanian, R. et al. Oral repletion of iron induces free radical mediated alterations in the gastrointestinal tract of rat. Mol Cell Biochem 219, 91–98 (2001). https://doi.org/10.1023/A:1011023111048
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DOI: https://doi.org/10.1023/A:1011023111048