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Open Access Research article

Zinc treatment ameliorates diarrhea and intestinal inflammation in undernourished rats

Camila AA de Queiroz1, Said Gonçalves C Fonseca4, Priscila B Frota1, Ítalo L Figueiredo1, Karoline S Aragão2, Carlos Emanuel C Magalhães1, Cibele BM de Carvalho3, Aldo Ângelo M Lima2, Ronaldo A Ribeiro2, Richard L Guerrant5, Sean R Moore6 and Reinaldo B Oriá12*

Author Affiliations

1 Laboratory of the Biology of Tissue Healing, Ontogeny and Nutrition, Department of Morphology and Institute of Biomedicine, School of Medicine, Federal University of Ceara, Rua Cel. Nunes de Melo, 1315, Fortaleza, CE, Brazil

2 Department of Physiology and Pharmacology and Institute of Biomedicine, School of Medicine, Federal University of Ceara, Rua Cel. Nunes de Melo, 1315, Fortaleza, CE, Brazil

3 Department of Microbiology and Institute of Biomedicine, School of Medicine, Federal University of Ceara, Rua Cel. Nunes de Melo, 1315, Fortaleza, CE, Brazil

4 Department of Pharmacy, Faculty of Pharmacy, Odontology, and Nursing, Federal University of Ceara, Rua Capitão Francisco Pedro, 1210, Fortaleza, CE, Brazil

5 Center for Global Health, Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA

6 Division of Gastroenterology, Hepatology, & Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

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BMC Gastroenterology 2014, 14:136  doi:10.1186/1471-230X-14-136

Published: 5 August 2014

Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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.

Keywords:
Zinc; Malnutrition; Diarrhea; Inflammation; Bacterial translocation