The online version of this article (doi:10.1186/1471-230X-14-136) contains supplementary material, which is available to authorized users.
All authors declare no competing of interest.
CCAQ, RLG, AAML, SRM, and RBO contributed with the study design, data analyses, and manuscript preparation. CCAQ, ILF, and PBF conducted animal handling and molecular biology analyses. SGCF worked in the diet manipulation and production. CCAQ and CBMC were responsible for the bacterial translocation experiments. CECM, RAR, and KSA conducted the serum zinc measurements and ELISA studies. All authors read and approved the final manuscript.
WHO guidelines recommend zinc supplementation as a key adjunct therapy for childhood diarrhea in developing countries, however zinc’s anti-diarrheal effects remain only partially understood. Recently, it has been recognized that low-grade inflammation may influence stunting. In this study, we examined whether oral zinc supplementation could improve weight, intestinal inflammation, and diarrhea in undernourished weanling rats.
Rats were undernourished using a northeastern Brazil regional diet (RBD) for two weeks, followed by oral gavage with a saturated lactose solution (30 g/kg) in the last 7 days to induce osmotic diarrhea. Animals were checked for diarrhea daily after lactose intake. Blood was drawn in order to measure serum zinc levels by atomic absorption spectroscopy. Rats were euthanized to harvest jejunal tissue for histology and cytokine profiles by ELISA. In a subset of animals, spleen samples were harvested under aseptic conditions to quantify bacterial translocation.
Oral zinc supplementation increased serum zinc levels following lactose-induced osmotic diarrhea. In undernourished rats, zinc improved weight gain following osmotic diarrhea and significantly reduced diarrheal scores by the third day of lactose intake (p < 0.05), with improved jejunum histology (p < 0.0001). Zinc supplementation diminished bacterial translocation only in lactose-challenged undernourished rats (p = 0.03) compared with the untreated challenged controls and reduced intestinal IL-1β and TNF-α cytokines to control levels.
Altogether our findings provide novel mechanisms of zinc action in the setting of diarrhea and undernutrition and support the use of zinc to prevent the vicious cycle of malnutrition and diarrhea.
Mitter SS, Oria RB, Kvalsund MP, Pamplona P, Joventino ES, Mota RM, Goncalves DC, Patrick PD, Guerrant RL, Lima AA: Apolipoprotein E4 influences growth and cognitive responses to micronutrient supplementation in shantytown children from northeast Brazil. Clinics (Sao Paulo). 2012, 67 (1): 11-18. CrossRef
Bushen OY, Davenport JA, Lima AB, Piscitelli SC, Uzgiris AJ, Silva TM, Leite R, Kosek M, Dillingham RA, Girao A, Lima AA, Guerrant RL: Diarrhea and reduced levels of antiretroviral drugs: improvement with glutamine or alanyl-glutamine in a randomized controlled trial in northeast Brazil. Clin Infect Dis. 2004, 38 (12): 1764-1770. CrossRefPubMed
Teodosio NR, Lago ES, Romani SA, Guedes RC: A regional basic diet from northeast Brazil as a dietary model of experimental malnutrition. Arch Latinoam Nutr. 1990, 40 (4): 533-547. PubMed
Ueno PM, Oria RB, Maier EA, Guedes M, de Azevedo OG, Wu D, Willson T, Hogan SP, Lima AA, Guerrant RL, Polk DB, Denson LA, Moore SR: Alanyl-glutamine promotes intestinal epithelial cell homeostasis in vitro and in a murine model of weanling undernutrition. Am J Physiol Gastrointest Liver Physiol. 2011, 301 (4): G612-G622. CrossRefPubMedPubMedCentral
Lastra MD, Pastelin R, Herrera MA, Orihuela VD, Aguilar AE: Increment of immune responses in mice perinatal stages after zinc supplementation. Arch Med Res. 1997, 28 (1): 67-72. PubMed
Ladd FV, Ladd AA, Ribeiro AA, Costa SB, Coutinho BP, Feitosa GA, de Andrade GM, de Castro-Costa CM, Magalhaes CE, Castro IC, Oliveira BB, Guerrant RL, Lima AA, Oria RB: Zinc and glutamine improve brain development in suckling mice subjected to early postnatal malnutrition. Nutrition. 2010, 26 (6): 662-670. CrossRefPubMedPubMedCentral
Azevedo OG, Oliveira RA, Oliveira BC, Zaja-Milatovic S, Araujo CV, Wong DV, Costa TB, Lucena HB, Lima RC, Ribeiro RA, Warren CA, Lima AA, Vitek MP, Guerrant RL, Oria RB: Apolipoprotein E COG 133 mimetic peptide improves 5-fluorouracil-induced intestinal mucositis. BMC Gastroenterol. 2012, 12: 35- CrossRefPubMedPubMedCentral
de Oliveira AT, da Silva TG, de Souza FE, Rezende Leite AC, de Moraes SR, de Sousa Maia MB: Impact of early malnourishment on the chronic inflammatory response and its implications for the effect of indomethacin on Wistar rats. Br J Nutr. 2011, 106 (6): 845-851. CrossRef
Carlson D, Poulsen HD, Vestergaard M: Additional dietary zinc for weaning piglets is associated with elevated concentrations of serum IGF-I. J Anim Physiol Anim Nutr (Berl). 2004, 88 (9–10): 332-339. CrossRef
Brown KH, Peerson JM, Rivera J, Allen LH: Effect of supplemental zinc on the growth and serum zinc concentrations of prepubertal children: a meta-analysis of randomized controlled trials. Am J Clin Nutr. 2002, 75 (6): 1062-1071. PubMed
Brown KH: Dietary management of acute diarrheal disease: contemporary scientific issues. J Nutr. 1994, 124 (8 Suppl): 1455S-1460S. PubMed
Greger JL, Gutkowski CM, Khazen RR: Interactions of lactose with calcium, magnesium and zinc in rats. J Nutr. 1989, 119 (11): 1691-1697. PubMed
Dewan P, Kaur IR, Faridi MM, Agarwal KN: Cytokine response to dietary rehabilitation with curd (Indian dahi) & leaf protein concentrate in malnourished children. Indian J Med Res. 2009, 130 (1): 31-36. PubMed
Fock RA, Vinolo MA, de Moura SR V, De Sa Rocha LC, Borelli P: Protein-energy malnutrition decreases the expression of TLR-4/MD-2 and CD14 receptors in peritoneal macrophages and reduces the synthesis of TNF-alpha in response to lipopolysaccharide (LPS) in mice. Cytokine. 2007, 40 (2): 105-114. CrossRefPubMed
Li X, Yin J, Li D, Chen X, Zang J, Zhou X: Dietary supplementation with zinc oxide increases Igf-I and Igf-I receptor gene expression in the small intestine of weanling piglets. J Nutr. 2006, 136 (7): 1786-1791. PubMed
Alves CX, Vale SH, Dantas MM, Maia AA, Franca MC, Marchini JS, Leite LD, Brandao-Neto J: Positive effects of zinc supplementation on growth, GH, IGF1, and IGFBP3 in eutrophic children. J Pediatr Endocrinol Metab. 2012, 25 (9–10): 881-887. PubMed
Bednorz C, Oelgeschlager K, Kinnemann B, Hartmann S, Neumann K, Pieper R, Bethe A, Semmler T, Tedin K, Schierack P, Wieler LH, Guenther S: The broader context of antibiotic resistance: zinc feed supplementation of piglets increases the proportion of multi-resistant Escherichia coli in vivo. Int J Med Microbiol. 2013, 303 (6–7): 396-403. CrossRefPubMed
Lima AA, Kvalsund MP, Souza PP, Figueiredo IL, Soares AM, Mota RM, Lima NL, Pinkerton RC, Patrick PP, Guerrant RL, Oria RB: Zinc, vitamin A, and glutamine supplementation in Brazilian shantytown children at risk for diarrhea results in sex-specific improvements in verbal learning. Clinics (Sao Paulo). 2013, 68 (3): 351-358. CrossRef
- Zinc treatment ameliorates diarrhea and intestinal inflammation in undernourished rats
Camila AA de Queiroz
Said Gonçalves C Fonseca
Priscila B Frota
Ítalo L Figueiredo
Karoline S Aragão
Carlos Emanuel C Magalhães
Cibele BM de Carvalho
Aldo Ângelo M Lima
Ronaldo A Ribeiro
Richard L Guerrant
Sean R Moore
Reinaldo B Oriá
- BioMed Central
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