Concurrent repletion of iron and zinc reduces intestinal oxidative damage in iron- and zinc-deficient rats

Abstract

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. 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 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 through 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.

The Role of Fe, Zn, and Cu in Pregnancy

“…Zn and Fe interact competitively during intestinal absorption [338]. In a study on animals, Bodiga and Krishnapillai [339] found that the interactions between Fe and Zn during absorption in Fe-and Zn-deficient rats are mutually antagonistic. The competition of Fe and Zn for metaltransporter1 (DMT-1) at the site of absorption results in reduced uptake of these elements during concurrent administration [340].…”

Extracellular Citrate Fuels Cancer Cell Metabolism and Growth

“…When intracellular Fe is low, IRP1 upregulates expression of proteins responsible for Fe uptake. In the presence of increased levels of intracellular Fe, IRP1 forms Fe-S clusters which prevent its binding to RNA; thus the protein loses its function as IRP1 but acquires activity of c-ACN (Bodiga and Krishnapillai, 2007;Wang et al, 2008). c-ACN metabolizes citrate into isocitrate which is then transformed into α-ketoglutarate with a concomitant synthesis of NADPH, the latter step mediated by cytosolic isocitrate dehydrogenases 1 and 2 (IDH1/2), which generate NADPH in contrast to the mitochondrial IDH (i.e., IDH3) which generates NADH.…”

Excess Dietary Zinc Intake in Neonatal Mice Causes Oxidative Stress and Alters Intestinal Host–Microbe Interactions

“…Consistent with these findings, our studies indicate that Zn accumulation in the intestine in vivo was also associated with oxidative stress, as a significantly greater number of 8OHdG + cells (approximately sixfold greater than in unsupplemented mice) were detected in the small intestine ( Figure ). Our studies are distinguished from prior reports that focused on the influence of therapeutic Zn supplementation in experimental animals made Zn deficient or subjected to intestinal damage . An important consideration is the Zn source.…”

“…Our studies are distinguished from prior reports that focused on the influence of therapeutic Zn supplementation in experimental animals made Zn deficient or subjected to intestinal damage. [36][37][38] An important consideration is the Zn source. We chose to use ZnSO 4 as many Zn supplements provide Zn as ZnSO 4 , and several comparative animal studies used ZnSO 4 .…”