title: Concurrent repletion of iron and zinc reduces intestinal oxidative damage in iron- and zinc-deficient rats.
abstract: OBJECTIVE
  To understand the interactions between iron and zinc during absorption in iron- and zinc-deficient rats, and their consequences on intestinal oxidant-antioxidant balance.
  
  
  METHODS
  Twenty-four weanling Wistar-Kyoto rats fed an iron- and zinc-deficient diet (< 6.5 mg Fe and 4.0 mg Zn/kg diet) for 4 wk were randomly divided into three groups (n = 8, each) and orally gavaged with 4 mg iron, 3.3 mg zinc, or 4 mg iron + 3.3 mg zinc for 2 wk. At the last day of repletion, 3 h before the animals were sacrificed, they received either 37 mBq of (55)Fe or (65)Zn, to study their localization in the intestine, using microautoradiography. Hemoglobin, iron and zinc content in plasma and liver were measured as indicators of iron and zinc status. Duodenal sections were used for immunochemical staining of ferritin and metallothionein. Duodenal homogenates (mitochondrial and cytosolic fractions), were used to assess aconitase activity, oxidative stress, functional integrity and the response of antioxidant enzymes.
  
  
  RESULTS
  Concurrent repletion of iron- and zinc-deficient rats showed reduced localization of these minerals compared to rats that were treated with iron or zinc alone; these data provide evidence for antagonistic interactions. This resulted in reduced formation of lipid and protein oxidation products and better functional integrity of the intestinal mucosa. Further, combined repletion lowered iron-associated aconitase activity and ferritin expression, but significantly elevated metallothionein and glutathione levels in the intestinal mucosa. The mechanism of interactions during combined supplementation and its subsequent effects appeared to be due to through modulation of cytosolic aconitase, which in turn influenced the labile iron pool and metallothionein levels, and hence reduced intestinal oxidative damage.
  
  
  CONCLUSIONS
  Concurrent administration of iron and zinc corrects iron and zinc deficiency, and also reduces the intestinal oxidative damage associated with iron supplementation.
authors.affiliation: Department of Biophysics, National Institute of Nutrition, Indian Council of Medical Research, Jamai-Osmania PO, Hyderabad 500007, Andhra Pradesh, India.
authors.forename: Sreedhar
authors.initials: S
authors.lastname: Bodiga
authors.forename: Madhavan Nair
authors.initials: MN
authors.lastname: Krishnapillai
mesh_terms: D000154:Aconitate Hydratase / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight; D003677:Deficiency Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D007501:Iron / Q000378:metabolism / Q000627:therapeutic use*; D000090463:Iron Deficiencies; D008668:Metallothionein / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D011921:Rats, Inbred WKY; D013482:Superoxide Dismutase / Q000378:metabolism; D015032:Zinc / Q000172:deficiency* / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D008668:Metallothionein; D007501:Iron; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D000154:Aconitate Hydratase; D015032:Zinc