Journal of Nutrition and Health

The Korean Nutrition Society (한국영양학회)
권호 표지
DOI QR코드

DOI QR Code

Effects of Iron Overload during Pregnancy on Oxidative Stress in Maternal Rats

임신 쥐의 철 과잉섭취가 조직의 산화적 스트레스에 미치는 영향

  • Park, Mi-Na (Department of Food and Nutrition & Research Institute of Human Ecology, Seoul National University) ;
  • Lee, Yeon-Sook (Department of Food and Nutrition & Research Institute of Human Ecology, Seoul National University)
  • 박미나 (서울대학교 식품영양학과/생활과학연구소) ;
  • 이연숙 (서울대학교 식품영양학과/생활과학연구소)
  • Received : 2010.10.25
  • Accepted : 2011.01.11
  • Published : 2011.02.28
Download PDF
⟨ Previous Next ⟩

Abstract

Although iron is an essential mineral, excess iron intake during pregnancy may increase oxidative stress in tissues. This study was conducted to investigate the effects of iron overload during pregnancy on iron status and oxidative stress in maternal rats. Ten week-old female Sprague-Dawley rats were mated with male rats. Non-pregnant (control) and pregnant rats were fed diets containing normal Fe (35 mg/kg diet), high Fe (350 mg/kg diet), or excess Fe (1,050 mg/kg diet) during pregnancy. Rats were sacrificed on pregnancy day 19. No significant difference in weight gain, diet intake, or litter size was observed according to iron intake levels. Furthermore, serum iron, hemoglobin, and hematocrit were not different among the rats administered the three levels of Fe both in the control and pregnant groups. However, the iron levels were lower in pregnant rats than those in the control. The liver and spleen iron contents increased significantly in the excess Fe group. An increase in liver ferritin levels with increasing iron intake was observed. Protein carbonyl content, as a marker of oxidative stress, increased significantly in liver with increasing iron intake but not malondialdehyde. Glutathione peroxidase activity in the liver of pregnant rats fed excess iron decreased significantly. Bcl-2 protein expression in the liver declined remarkably with increasing maternal iron intake in pregnant rats. Taken together, iron overload during pregnancy had little effect on hematology. However, the deposits of iron in the liver and the decline in antioxidant enzyme activity implied increased oxidative stress in tissues of the excess Fe group. These results suggest that excess iron intake during pregnancy increases oxidative stress in maternal tissues and may also affect fetal tissues.

본 연구는 임신기 동안 어미쥐의 철 섭취 수준이 모체의 철 대사지표와 산화적 스트레스 및 임신의 결과에 미치는 영향을 검토하기 위해 비임신쥐를 대조군으로 하여 수행하였다. 10주령 200 g 이상 된 암컷과 수컷 흰쥐를 1 : 1로 교배시켜 임신을 확인한 후, 비임신쥐 (대조군)와 임신쥐 (실험군)에게 식이 중 철 수준이 정상수준 (AIN-93G diet 수준, 35 mg Fe/kg diet), 고수준 (정상의 10배, 350 mg Fe/kg diet) 및 과잉수준 (정상의 30배, 1,050 mg Fe/kg diet)의 3가지 실험식이를 급여하였다. 임신 19일째 되는 날, 비임신쥐와 임신 쥐를 희생시켜 분석한 결과는 다음과 같다. 체중의 증가나 식이섭취량은 철 섭취 수준의 영향을 받지 않았고, 임신의 결과로서 태아의 수, 태아체중 및 태반무게도 철 섭취 수준의 영향은 받지 않았다. 헤모글로빈, 헤마토크릿, 혈청 철 농도 등의 혈액지표들은 철 섭취 수준의 영향은 받지 않았으나 임신에 의한 감소 경향을 보였다. 임신쥐의 철 섭취 수준의 증가에 따라 간과 지라 조직의 철 함량이 유의적으로 증가하였다. 또한 임신쥐의 간에서 페리틴 단백질 수준이 철 섭취의 증가에 따라 현저히 증가하였다. 산화적 손상지표인 지질과산화물 (MDA)은 철 섭취수준의 영향을 받지 않았고, 단백질 산화물 (protein carbonyls)은 비임신쥐와 임신쥐에서 모두 철 과잉 섭취군의 경우 유의적으로 증가하였다. 항산화효소 중에서는 철 과잉섭취군에서 간의 GPx 활성이 유의적으로 감소하였다. 결론적으로, 임신기 동안 어미쥐의 철 섭취수준의 증가는 어미쥐의 혈액지표와 임신의 결과에는 유의적인 영향을 미치지 않았지만, 간 조직 내 철 함량과 페리틴 단백질 수준을 유의적으로 증가시켰으며, 간 조직에서 단백질 산화물인 protein carbonyl 농도를 증가시키고, 항산화효소 중 특히 GPx의 활성 감소를 초래하였다. 또한 간 조직에서 세포사멸을 억제하는 중요한 인자인 Bcl-2 단백질 수준이 임신쥐에서 철 섭취의 증가에 따라 유의적으로 감소하였다. 이러한 영향이 철을 정상 수준의 10배 섭취한 군에서는 약하게 나타났으나, 30배 과잉으로 철을 섭취한 군에서는 유의적으로 차이를 보였다. 이 결과는 임신시 철 과잉 섭취의 해로운 영향이 지금까지 철 대사의 측정도구로 삼아왔던 혈액지표의 변화 보다는 체내에서 일어나는 조직의 산화적 스트레스의 증가나 조직 내 철의 축적 등에 보다 더 민감하게 반영됨을 알 수 있었다. 따라서, 철 과잉 섭취가 모체 뿐만 아니라 태생 조직의 산화적 스트레스에도 영향을 줄 수 있음을 시사하였다.

Keywords

References

  1. Aisen P, Enns C, Wessling-Resnick M. Chemistry and biology of eukaryotic iron metabolism. Int J Biochem Cell Biol 2001; 33(10): 940-959
  2. Swanson CA. Iron intake and regulation: implications for iron deficiency and iron overload. Alcohol 2003; 30(2): 99-102
  3. Levenson CW, Tassabehji NM. Iron and ageing: an introduction to iron regulatory mechanisms. Ageing Res Rev 2004; 3(3): 251-263
  4. Ministry of Health & Welfare, 2008 the Report of Korean National Health & Nutrition Examination Survey; 2009
  5. Cho JH, Ahn HS, Bae HS. The use of iron supplements of pregnant women and pregnancy outcome. Korean J Community Nutr 2009; 14(3): 327-339
  6. Casanueva E, Viteri FE. Iron and oxidative stress in pregnancy. J Nutr Suppl 2 2003; 133(5): S1700-S1708
  7. Southon S, Wright AJ, Fairweather-Tait SJ. The effect of differences in dietary iron intake on 59Fe absorption and duodenal morphology in pregnant rats. Br J Nutr 1989; 62(3): 707-717
  8. Barrett JFR, Whittaker PG, Williams JG, Lind T. Absorption of nonhaem iron from food during normal pregnancy. Br Med J 1994; 309: 79-82
  9. Long PJ. Rethinking iron supplementation during pregnancy. J Nurse Midwifery 1995; 40(1): 36-40
  10. Scholl TO. High third-trimester ferritin concentration: associations with very preterm delivery, infection, and maternal nutritional status. Obstet Gynecol 1998; 92: 161-166
  11. Kim YJ, Hong YC, Lee KH, Park HJ, Park EA, Moon HS, Ha EH. Oxidative stress in pregnant women and birth weight reduction. Reprod Toxicol 2005; 19: 487-492
  12. Atamer Y, Kocyigit Y, Yokus B, Atamer A, Erden AC. Lipid peroxidation, antioxidant defense, status of trace metals and leptin levels in preeclampsia. Eur J Obstet Gynecol Reprod Biol 2005; 119(1): 60-66
  13. Vanderlelie J, Venardos K, Clifton L, Gude NM, Clarke FM, Perkins AV. Increased Biological Oxidation and Reduced Antioxidant Enzyme Activity in Pre-eclamptic Placentae. Placenta 2005; 26: 53-58
  14. Sorenson CM. Bcl-2 family members and disease. Biochim Biophys Acta 2004; 1644(2-3): 169-177
  15. Motoyama S, Saito S, Saito R, Minamiya Y, Nakamura M, Okuyama M, Imano H, Ogawa J. Hydrogen peroxide-dependent declines in Bcl-2 induce apoptosis in hypoxic liver. J Surg Res 2003; 110(1): 211-216
  16. Reeves PG, Nielsen FH, Fahey Jr GC. 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 1993; 123: 1939-1951
  17. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by Thiobarbituric acid reaction. Anal Biochem 1979; 95: 351-358
  18. Levine RL, Garland D, Oliver CN, Amici A, Climent I, Lenz AG, Ahn B, Shaltiel S, Stadtman ER. Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol 1990; 186: 464-478
  19. Aebi H. Catalase in Vitro. Method Enzymol 1984; 105: 121-126
  20. Kochanowski BA, Sherman AR. Iron status of suckling rats as influenced by maternal diet during gestation and lactation. Br J Nutr 1983; 49(1): 51-57
  21. Southon S, Wright AJ, Fairweather-Tait SJ. The effect of differences in dietary iron intake on 59Fe absorption and duodenal morphology in pregnant rats. Br J Nutr 1989; 62(3): 7070-717
  22. Finch CA, Huebers HA, Miller LR, Josephson BM, Shepard TH, Mackler B. Fetal iron balance in the rat. Am J Clin Nutr 1983; 37(6): 910-917
  23. Sochaski MA, Bartfay WJ, Thorpe SR, Baynes JW, Bartfay E, Lehotay DC, Liu PP. Lipid peroxidation and protein modification in a mouse model of chronic iron overload. Metabolism 2002; 51(5): 645-651
  24. Lin WJ, Kirksey A. Effects of different levels of dietary iron on pregnancy superimposed upon growth in the rat. J Nutr 1976; 106: 543-554
  25. Tran T, Wax JR, Philput C, Steinfeld JD, Ingardia CJ. Intentional iron overdose in pregnancymanagement and outcome. J Emerg Med 2000; 18(2): 225-228
  26. Van den Broek N. Anemia and micronutrient deficiencies. Br Med Bull 2003; 67: 149-160
  27. Kang BH, Son HY, Ha CS, Lee HS, Song SW. Reference Values of Hematology and Serum Chemistry in Ktc: Sprague-Dawely Rats. Korean J Lab Anim Sci 1995; 11(2): 141-145
  28. Nair KM, Bhaskaram P, Balakrishna N, Ravinder P, Sesike B. Response of hemoglobin, serum ferritin, and serum transferrin receptor during iron supplementation in pregnancy: A prospective study. Nutrition 2004; 20(10): 896-899
  29. Lee JI, Kang SA, Kim SK, Lim HS. A cross sectional study of maternal iron status of Korean women during pregnancy. Nutr Res 2002; 22(12): 1377-1388
  30. Cogswell ME, Parvanta I, Ickes L, Yip R, Brittenham GM. Iron supplementation during pregnancy, anemia, and birth weight: a randomized controlled trial. Am J Clin Nutr 2003; 78: 773-781
  31. Sherman AR, Moran PE. Copper metabolism in iron-deficient maternal and neonatal rats. J Nutr 1984; 114(2): 298-306
  32. Bashiri A, Burstein E, Sheiner E, Mazor M. Anemia during pregnancy and treatment with intravenous iron: review of the literature. Eur J Obstet Gynecol Reprod Biol 2003; 110: 2-7
  33. Bresgen N, Jaksch H, Lacher H, Ohlenschlager I, Uchida K, Eckl PM. Iron-mediated oxidative stress plays an essential role in ferritin-induced cell death. Free Radic Biol Med 2010; 48: 1347-1357
  34. Templeton DM, Liu Y. Genetic regulation of cell function in response to iron overload or chelation. Biochim Biophys Acta 2003; 1619(2):113-124
  35. Khan MF, Wu X, Tipnis UR, Ansari GA, Boor PJ. Protein adducts of malondialdehyde and 4-hydroxynonenal in livers of iron loaded rats: quantitation and localization. Toxicology 2002; 173(3): 193-201
  36. Knutson MD, Walter PB, Ames BN, Viteri FE. Both iron deficiency and daily iron supplements increase lipid peroxidation in rats. J Nutr 2000; 130(3): 621-628
  37. Srigiridhar K, Nair KM. Iron-deficient intestine is more susceptible to peroxidative damage during iron supplementation in rats. Free Radic Biol Med 1998; 25(6): 660-665
  38. Brady HJ, Gil-Gomez G. Bax: the pro-apoptotic Bcl-2 family member. Int J Biochem Cell Biol 1998; 30(6): 647-650

Cited by

  1. Changes in the Nutritional Compositions of Soybean Sprouts Cultivated with Bamboo Ash vol.31, pp.3, 2016, https://doi.org/10.7318/KJFC/2016.31.3.213