Basic Research
Copyright ©2007 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 21, 2007; 13(43): 5707-5717
Published online Nov 21, 2007. doi: 10.3748/wjg.v13.i43.5707
Concurrent repletion of iron and zinc reduces intestinal oxidative damage in iron- and zinc-deficient rats
Sreedhar Bodiga, Madhavan Nair Krishnapillai
Sreedhar Bodiga, Madhavan Nair Krishnapillai, Department of Biophysics, National Institute of Nutrition, Hyderabad 500007, Andhra Pradesh, India
Author contributions: All authors contributed equally to the work.
Supported by the Indian Council of Medical Research
Correspondence to: Dr. Madhavan Nair Krishnapillai, Department of Biophysics, National Institute of Nutrition, Indian Council of Medical Research, Jamai-Osmania PO, Hyderabad 500007, Andhra Pradesh, India.
Telephone: +91-40-27008921 Fax: +91-40-27019074
Received: June 15, 2007
Revised: August 16, 2007
Accepted: October 12, 2007
Published online: November 21, 2007

AIM: 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. On the last day of repletion, 3 h before the animals were sacrificed, they received either 37 mBq of 55Fe or 65Zn, 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 teated 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 modulation of cytosolic aconitase, which in turn influenced the labile iron pool and metallothionein levels, and hence reduced intestinal oxidative damage.

CONCLUSION: Concurrent administration of iron and zinc corrects iron and zinc deficiency, and also reduces the intestinal oxidative damage associated with iron supplementation.

Keywords: Iron, Zinc, Absorption, Intestine, Aconitase, Ferritin, Metallothionein, Oxidative damage