Vitamin A does not influence mRNA expression of hormone hepcidin but other biomarkers of iron homeostasis in young male Wistar rats
Abstract
Abstract. The effects of an adequate supply of vitamin A and iron, in comparison with diets low or absent in vitamin A and low in iron, on the mRNA expression of some biomarkers of iron homeostasis as hepcidin (Hamp), transferrin receptor-1 (Tfrc), iron regulatory protein-2 (Ireb2) and ferritin (Fth1) in rats were investigated. 35 male Wistar rats were randomly divided into 5 dietary groups: control, sufficient in iron and insufficient in vitamin A (FesvAi), sufficient in iron and depleted in vitamin A (FesvAd), insufficient in iron and sufficient in vitamin A (FeivAs) and insufficient in both iron and vitamin A (FeivAi). After 6 weeks rats showed no significant effects of variations in vitamin A on the expression of Hamp relative to the control group (FesvAi: 1.37-fold; FesvAd: 1.22-fold); however, iron deficiency showed significant reduction on it relative to the control group (FeivAs: 71.4-fold, P = 0.0004; FeivAi: 16.1-fold, P = 0.0008). Vitamin A deficiency (FesvAd) affects expression of Fth1 independent of low dietary iron in spleen (0.29-fold, P = 0.002) and duodenum (5.15-fold, P = 0.02). Variations of dietary iron and vitamin A showed significant effects relative to the control group for expression of Tfrc in spleen (FesvAd: 0.18-fold, P = 0.01; FeivAs: 0.24-fold, P < 0.0001; FeivAi: 0.42-fold, P = 0.014), Ireb2 in spleen (FeivAs: 3.7-fold, P < 0.0001; FeivAi: 2.9-fold, P < 0.0001) and Ireb2 in duodenum (FeivAs: 2.68-fold, P = 0.012; FeivAi: 2.60-fold, P = 0.014). These results show that vitamin A and iron must be supplied together to regulate some of the main biomarkers of iron metabolism as a strategy to reduce prevalence of iron deficiency anemia.
References
1 . The global hidden hunger indices and maps: An advocacy tool for action. PLoS One. 2013;8(6):1–12.
2 . Health in 2015: From MDGs, Millennium Development Goals to SDGs, Sustainable Development Goals. Geneva: WHO; 2015.
3 . The global prevalence of anaemia in 2011. Geneva: WHO; 2015.
4 . Vitamin A deficiency disorders in children and women. Food Nutr Bull. 2003;24(Suppl 4):78–90.
5 . Global prevalence of vitamin A deficiency in populations at risk 1995–2005: WHO global database on vitamin A deficiency. Geneva: WHO; 2009.
6 . Dietary and physiological factors that affect the absorption and bioavailability of iron. Int J Vitam Nutr Res. 2005;75(6):375–84.
7 . Intestinal iron absorption. J Trace Elem Med Biol. 2012;26:115–9.
8 . Anemia. Hematol Oncol Clin North Am. 2017;31(6):1045–60.
9 . Iron deficiency anaemia. Paediatr Child Health (Oxford). 2017;27(11):527–9.
10 . Anemia: Evaluation and diagnostic tests. Med Clin North Am. 2017;101(2):263–84.
11 . Iron homeostasis: Fitting the puzzle pieces together. Cell Metab. 2008;7(4):288–90.
12 . Hepcidin: A novel peptide hormone regulating iron metabolism. Clin Chim Acta. 2011;412:823–30.
13 Pathways for the regulation of hepcidin expression in anemia of chronic disease and iron deficiency anemia in vivo. Haematologica. 2011;96(12):1761–9.
14 . Vitamin A deficiency modulates iron metabolism via ineffective erythropoiesis. J Nutr Biochem. 2014;25(10):1035–44.
15 . Iron deficiency and anemia are associated with low retinol levels in children aged 1 to 5 years. J Pediatr (Rio J). 2014;90(6):593–9.
16 . Antioxidants mediate both iron homeostasis and oxidative stress. Nutrients. 2017;9(7):1–19.
17 . Effect of vitamin A supplementation on iron status in humans: A systematic review and meta-analysis. Crit Rev Food Sci Nutr. 2019;59(11):1767–81.
18 . Vitamin A deficiency increases hepcidin expression and oxidative stress in rat. Nutrition. 2009;25(4):472–8.
19 . Vitamin a modulates the expression of genes involved in iron bioavailability. Biol Trace Elem Res. 2012;149(1):64–70.
20 . Components of the AIN-93 diets as improvements in the AIN-76A diet. J Nutr. 1997;127:838S–841S.
21 . How to calculate sample size in animal studies? J Pharmacol Pharmacother. 2013;4(4):303.
22 . Eficácia da suplementação de ferro associado ou não à vitamina A no controle da anemia em escolares. Cad Saúde Pública. 2007;23(6):1415–21.
23 Nutrient patterns and its relation to anaemia and iron status in 5–12-year-old children in South Africa. Nutrition. 2019;62:194–200.
24 . An efficacy study on alleviating micronutrient deficiencies through a multiple micronutrient fortified salt in children in South India. Asia Pac J Clin Nutr. 2014;23(3):413–22.
25 . Prevalence of anaemia, deficiencies of iron and vitamin A and their determinants in rural women and young children: A cross-sectional study in Kalalé district of northern Benin. Public Health Nutr. 2017;20(7):1203–13.
26 . Influence of iron on vitamin a nutritional status. Nutr Rev. 2008;66(3):141–7.
27 . Regulation of hepcidin transcription by interleukin-1 and interleukin-6. Proc Natl Acad Sci. 2005;102(6):1906–10.
28 . Molecular mechanisms of hepcidin regulation: Implications for the anemia of CKD. Am J Kidney Dis. 2010;55(4):726–41.
29 . Modulation of hepcidin as therapy for primary and secondary iron overload disorders: Preclinical models and approaches. Hematol Oncol Clin North Am. 2014;28(2):387–401.
30 . Effect of vitamin A deficiency on iron metabolism and hepcidin mRNA expression in rat. Proceedings 2011 International Conference on Human Health and Biomedical Engineering. 2011;140–2.
31 . Vitamin A deficiency aggravates iron deficiency by upregulating the expression of iron regulatory protein-2. Nutrition. 2012;28(3):281–7.
32 . The IRP/IRE system in vivo: Insights from mouse models. Front Pharmacol. 2014;5:1–15.
33 Heatmapper: Web-enabled heat mapping for all. Nucleic Acids Res. 2016;44(W1):W147–53.
34 . Vitamin A deficiency modulates iron metabolism independent of hemojuvelin (Hfe2) and bone morphogenetic protein 6 (Bmp6) transcript levels. Genes Nutr. 2016;11(1):1–7. https://doi.org/10.1186/s12263-016-0519-4.
35 Sex differences in iron status and hepcidin expression in rats. Biol Trace Elem Res. 2014;160(2):258–67.
36 . Reabsorption of iron into acutely damaged rat liver: A role for ferritins. World J Gastroenterol. 2017;23(41):7347–58.
37 Comparison of changes in gene expression of transferrin receptor-1 and other iron-regulatory proteins in rat liver and brain during acute-phase response. Cell Tissue Res. 2011;344(2):299–312.
38 Hepcidin and hemojuvelin gene expression in rat liver damage: In vivo and in vitro studies. Am J Physiol Liver Physiol. 2006;291(3):G482–90.