Vitamin A deficiency regulates the expression of ferritin in young male Wistar rats
Palavras-chave:
Ferritin, Iron deficiency, Receptors, transferrin, Vitamin A deficiencyResumo
Objective
Iron deficiency and vitamin A deficiency are two of the main micronutrient deficiencies. Both micronutrients are essential for human life and children’s development. This study aimed to investigate the effects of vitamin A deficiency on ferritin and transferrin receptors’ expression and its relationship with iron deficiency.
Methods
Five diets with different vitamin A-to-iron ratios were given to thirty five 21-day-old male Wistar rats (separated ingroups of seven animals each). The animals received the diet for six weeks before being euthanized. Serum iron and retinol levels were measured as biochemical parameters. Their duodenums, spleens, and livers were analyzed for theexpression of ferritin and transferrin receptors by Western Blotting.
Results
Regarding biochemical parameters, the results show that when both vitamin A and iron are insufficient, the serum iron content (74.74µg/dL) is significantly lower than the control group (255.86µg/dL). The results also show that vitamin A deficiency does not influence the expression of the transferrin receptor, but only of the ferritin one.
Conclusion
Vitamin A deficiency regulates the expression of ferritin in young male Wistar rats.
Referências
Muthayya S, Rah JH, Sugimoto JD, Roos FF, Kraemer K, Black RE. The global hidden hunger indices and maps: an advocacy tool for action. Plos One. 2013;8:e67860. https://doi.org/10.1371/journal.pone.0067860
Arcanjo FPN, Arcanjo CPC, Santos PR. Schoolchildren with learning difficulties have low iron status and high anemia prevalence. J Nutr Metab. 2016;2016:1-5. https://doi.org/10.1155/2016/7357136
World Health Organization. Health in 2015: from MDGs, Millennium Development Goals to SDGs, Sustainable Development Goals. Geneva: Organization; 2015.
Cediel G, Olivares M, Gaitán D, Flores S, Brito A, Pizarro F. Effect of trypsin and mucin on heme iron bioavailability in humans. Biol Trace Elem Res. 2012;150:37-41. https://doi.org/10.1007/s12011-012-9483-9
Gulec S, Anderson GJ, Collins JF. Mechanistic and regulatory aspects of intestinal iron absorption. Am J Physiol Gastrointest Liver Physiol. 2014;307:G397-409. https://doi.org/10.1152/ajpgi.00348.2013
Grotto HZW. Metabolismo do ferro: uma revisão sobre os principais mecanismos envolvidos em sua homeostase Iron metabolism: an overview on the main mechanisms involved in its homeostasis. Rev Bras Hematol Hemoter 2008;5:390-7. https://doi.org/10.1590/S1516-84842008000500012
Sheikh N, Batusic DS, Dudas J, Tron K, Neubauer K, Saile B, et al. Hepcidin and hemojuvelin gene expression in rat liver damage: in vivo and in vitro studies. Am J Physiol Liver Physiol. 2006;291:82-90. https://doi.org/10.1152/ajpgi.00586.2005
Lee P, Peng H, Gelbart T, Wang L, Beutler E. Regulation of hepcidin transcription by interleukin-1 and interleukin-6. Proc Natl Acad Sci. 2005;102:1906-10. https://doi.org/10.1073/pnas.0409808102
Babitt JL, Lin HY. Molecular mechanisms of hepcidin regulation: implications for the anemia of CKD. Am J Kidney Dis. 2010;55:726-41. https://doi.org/10.1053/j.ajkd.2009.12.030
Nakagawa H, Tamura T, Mitsuda Y, Goto Y, Kamiya Y, Kondo T, et al. Inverse correlation between serum interleukin-6 and iron levels among Japanese adults: a cross-sectional study. BMC Hematol; 14. Epub ahead of print. 2014. https://doi.org/10.1186/2052-1839-14-6
Wong C. Iron deficiency anaemia. Paediatr Child Health (Oxford). 2017;27:527-9.
André HP, Vieira SA, Franceschini SCC, Ribeiro AQ, Hermsdorff HHM, Priore SE. Factors associated with the iron nutritional status of Brazilian children aged 4 to 7 years. Rev Nutr. 2017;30:345-55. https://doi.org/10.1590/1678-98652017000300007
Cascio MJ, De Loughery TG. Anemia: evaluation and diagnostic tests. Med Clin North Am. 2017;101:263-84. https://doi.org/10.1016/j.mcna.2016.09.003
De La Cruz-Góngora V, Salinas-Rodríguez A, Villalpando S, Flores-Aldana M. Serum retinol but not 25(OH)D status is associated with serum hepcidin levels in older Mexican adults. Nutrients. 2019;11:1-15. https://doi.org/10.3390%2Fnu11050988
Green R, Mitra AD. Megaloblastic anemias: nutritional and other causes. Med Clin North Am. 2017;101:297-317. https://doi.org/10.1016/j.mcna.2016.09.013
Pedraza DF. Vitamin A deficiency in brazilian children younger than 5 years old: a systematic review. Rev Bras Saúde Matern Infant. 2020;20:667-79. https://doi.org/10.1590/1806-93042020000300002
Rubino P, Mora P, Ungaro N, Galdolfi SA, Orsoni JG. Anterior segment findings in vitamin a deficiency: a case series. Case Rep Ophthalmol Med. 2015;2015:1-6. https://doi.org/10.1155/2015/181267
Koessler KK, Maurer S, Loughlin R. The relation of anemia, primary and secondary, to vitamin A deficiency. Jama. 1926;87:476-82. https://doi.org/10.1001/jama.1926.02680070022006
Cunha MSB, Campos Hankins NA, Arruda SF. Effect of vitamin A supplementation on iron status in humans: a systematic review and meta-analysis. Crit Rev Food Sci Nutr. 2019;59:1767-81. https://doi.org/10.1080/10408398.2018.1427552
Villalpando S, de la Cruz V, Shamah-Levy T, Rebollar R, Contreras-Manzano A. Nutritional status of iron, vitamin B12, folate, retinol and anemia in children to 11 years old. Results of the Ensanut 2012. Salud Publica Mex. 2015;57:372-84.
Michelazzo FB, Oliveira JM, Stefanello J, Luzia LA, Rondó PH. The influence of vitamin A supplementation on iron status. Nutrients. 2013;5:4399-413. https://doi.org/10.3390%2Fnu5114399
Mendes JF, Siqueira EM, Brito E Silva JG, Arruda SF. Vitamin A deficiency modulates iron metabolism independent of hemojuvelin (Hfe2) and bone morphogenetic protein 6 (Bmp6) transcript levels. Genes Nutr. 2016;11:1-7. https://doi.org/ 10.1186/s12263-016-0519-4
Saraiva BC, Soares MC, Santos LC, Pereira SC, Horta PM. Iron deficiency and anemia are associated with low retinol levels in children aged 1 to 5 years. J Pediatr (Rio J). 2014;90:593-9. https://doi.org/10.1016/j.jped.2014.03.003
Imam MU, Zhang S, Ma J, Wang H, Wang F. Antioxidants mediate both iron homeostasis and oxidative stress. Nutrients. 2017;9:1-19. https://doi.org/10.3390/nu9070671
Arruda SF, Siqueira EMA, Valência FF. Vitamin A deficiency increases hepcidin expression and oxidative stress in rat. Nutrition. 2009;25:472-8. https://doi.org/10.1016/j.nut.2008.11.030
Citelli M, Bittencourt LL, da Silva SV, Pierucci AP, Pedrosa C. Vitamin A modulates the expression of genes involved in iron bioavailability. Biol Trace Elem Res. 2012;149:64-70. https://doi.org/10.1007/s12011-012-9397-6
Bartnikas TB, Fleming MD, Schmidt PJ. Murine mutants in the study of systemic iron metabolism and its disorders: an update on recent advances. Biochim Biophys Acta Mol Cell Res. 2012;1823:1444-50. https://doi.org/10.1016/j.bbamcr.2012.01.011
Baker DH. Animal models in nutrition research. J Nutr. 2008;138:391-6. https://doi.org/10.1093/jn/138.2.391
Italia K, Colah R, Ghosh K. Experimental animal model to study iron overload and iron chelation and review of other such models. Blood Cells Mol Dis. 2015;55:194-9. https://doi.org/10.1016/j.bcmd.2015.06.003
García Y, Díaz-Castro J. Advantages and disadvantages of the animal models v. in vitro studies in iron metabolism: a review. Animal. 2013;7:1651-8. https://doi.org/10.1017/S1751731113001134
Restrepo-Gallego M, Díaz LE. Influence of dietary vitamin A and iron deficiency on hematologic parameters and body weight of young male wistar rats. J Am Assoc Lab Anim Sci. 2020;59:17-23. https://doi.org/10.30802/aalasjaalas-19-000020
Du Sert NP, Hurst V, Ahluwalia A, Alam S, Avey MT, Baker M, et al. The arrive guidelines 2.0: updated guidelines for reporting animal research. Plos Biol. 2020;18:1-12. https://doi.org/10.1371/journal.pbio.3000410
Ricci C, Baumgartner J, Malan L, Smuts CM. Determining sample size adequacy for animal model studies in nutrition research: limits and ethical challenges of ordinary power calculation procedures. Int J Food Sci Nutr. 2020;71:256-64. https://doi.org/10.1080/09637486.2019.1646714
Yokoi K. Investigating the essentiality and requirements of iron from the ancient to the present. Biol Trace Elem Res. 2019;188:140-7. https://doi.org/10.1007/s12011-018-1584-7
Wirth JP, Rohner F, Woodruff BA, Chiwile F, Yankson H, Koroma AS, et al. Anemia, micronutrient deficiencies, and malaria in children and women in Sierra Leone prior to the Ebola outbreak: findings of a cross-sectional study. Plos One. 2016;11:1-22. https://doi.org/10.1371/journal.pone.0155031
Tanumihardjo SA. WHO Report: piorities in the assessment of timan A and iron status in populations. Biomarkers of vitamin A status: what do they mean? Geneva: World Heal Organization; 2010;15-7.
Thakur M, Kulkarni SS, Mohanty N, Kadam NN, Swain N. Standardization & development of rat model with iron deficiency anaemia utilising commercial available iron deficient food. Biosci Biotechnol Res Asia. 2019;16:71-7. https://doi.org/10.13005/bbra/2722
National Research Council. Nutrient requirements of laboratory animals, 2015. Epub ahead of print. 2015. https://doi.org/10.17226/4758
Namaste SML, Rohner F, Huang J, Bhushan NL, Flores-Ayala R, Kupka R, et al. Adjusting ferritin concentrations for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project. Am J Clin Nutr. 2017;106:359-71. https://doi.org/10.3945/ajcn.116.141762
Rohner F, Namaste SML, Larson LM, Addo OY, Mei Z, Suchdev PS, et al. Adjusting soluble transferrin receptor concentrations for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project. Am J Clin Nutr. 2017;106:372-82. https://doi.org/10.3945/ajcn.116.142232
Cichon B, Ritz C, Fabiansen C, Christensen VB, Filteau S, Friis H, et al. Assessment of regression models for adjustment of iron status biomarkers for inflammation in children with moderate acute malnutrition in Burkina Faso. J Nutr. 2016;126-32. https://doi.org/10.3945/jn.116.240028
Malik IA, Wilting J, Ramadori G, Naz N. Reabsorption of iron into acutely damaged rat liver: a role for ferritins. World J Gastroenterol. 2017;23:7347-58. https://doi.org/10.3748/wjg.v23.i41.7347
Jiang S, Wang C, Lan L, Zhao D. Vitamin A deficiency aggravates iron deficiency by upregulating the expression of iron regulatory protein-2. Nutrition. 2012;28:281-7. https://doi.org/10.1016/j.nut.2011.08.015
Ferreira KPZ, Oliveira SR, Kallaur AP, Kaimen-Maciel DR, Lozovoy MAB, Almeida ERD, et al. Disease progression and oxidative stress are associated with higher serum ferritin levels in patients with multiple sclerosis. J Neurol Sci. 2017;373:236-41. https://doi.org/10.1016/j.jns.2016.12.039
Cunha MSB, Siqueira EMA, Trindade LA, Arruda SF. Vitamin A deficiency modulates iron metabolism via ineffective erythropoiesis. J Nutr Biochem. 2014;25:1035-44. https://doi.org/10.1016/j.jnutbio.2014.05.00546. Suega K, Widiana GR. Predicting hepcidin level using inflammation markers and iron indicators in patients with anemia of chronic disease. Hematol Transfus Cell Ther. 2019;41:342-8. https://doi.org/ 10.1016/j.htct.2019.03.011
Bergamaschi G, Di Sabatino A, Pasini A, Ubezio C, Constanzo F, Grataroli D, et al. Intestinal expression of genes implicated in iron absorption and their regulation by hepcidin. Clin Nutr. 2017;36:1427-33. https://doi.org/10.1016/j.clnu.2016.09.021
Zhang J, Chen X, Hong J, Tang A, Liu Y, Xie N, et al. Biochemistry of mammalian ferritins in the regulation of cellular iron homeostasis and oxidative responses. Sci China Life Sci. Epub ahead of print 2020. https://doi.org/10.1007/s11427-020-1795-4
Suárez-Ortegón MF, Ensaldo-Carrasco E, Shi T, McLachlan S, Fernández-Real JM, Wild SH. Ferritin, metabolic syndrome and its components: a systematic review and meta-analysis. Atherosclerosis. 2018;275:97-106. https://doi.org/10.1016/j.atherosclerosis.2018.05.043
Li Y, Wei CH, Xiao X, Green MH, Ross AC. Perturbed vitamin A status induced by iron deficiency is corrected by iron repletion in rats with pre-existing iron deficiency. J Nutr. 2020;150:1989-95. https://doi.org/10.1093/jn/nxaa10851. Han L, Liu Y, Lu M, Wang H, Tang F. Retinoic acid modulates iron metabolism imbalance in anemia of inflammation induced by LPS via reversely regulating hepcidin and ferroportin expression. Biochem Biophys Res Commun. 2018;507:280-5. https://doi.org/10.1016/j.bbrc.2018.11.022
Lu Z, O’Dell D, Srinivasan B, Rey E, Wang R, Vemulapati S, et al. Rapid diagnostic testing platform for iron and Vitamin A deficiency. Proc Natl Acad Sci USA. 2017;114 13513-8. https://doi.org/10.1073/pnas.1711464114
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Copyright (c) 2022 Mauricio RESTREPO-GALLEGO, Luis Eduardo DÍAZ, Juan David OSPINA-VILLA, Danny CHINCHILLA-CÁRDENAS
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