title: Zinc treatment ameliorates diarrhea and intestinal inflammation in undernourished rats.
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.
  
  
  CONCLUSIONS
  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.
authors.forename: Camila A A
authors.initials: CA
authors.lastname: de Queiroz
authors.forename: Said Gonçalves C
authors.initials: SG
authors.lastname: Fonseca
authors.forename: Priscila B
authors.initials: PB
authors.lastname: Frota
authors.forename: Italo L
authors.initials: IL
authors.lastname: Figueiredo
authors.forename: Karoline S
authors.initials: KS
authors.lastname: Aragão
authors.forename: Carlos Emanuel C
authors.initials: CE
authors.lastname: Magalhães
authors.forename: Cibele B M
authors.initials: CB
authors.lastname: de Carvalho
authors.forename: Aldo Ângelo M
authors.initials: AÂ
authors.lastname: Lima
authors.forename: Ronaldo A
authors.initials: RA
authors.lastname: Ribeiro
authors.forename: Richard L
authors.initials: RL
authors.lastname: Guerrant
authors.forename: Sean R
authors.initials: SR
authors.lastname: Moore
authors.affiliation: 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. rbo5u@virginia.edu.
authors.forename: Reinaldo B
authors.initials: RB
authors.lastname: Oriá
mesh_terms: D000818:Animals; D018988:Bacterial Translocation / Q000187:drug effects*; D003967:Diarrhea / Q000188:drug therapy*; D004195:Disease Models, Animal; D004751:Enteritis / Q000188:drug therapy*; D053583:Interleukin-1beta / Q000187:drug effects / Q000276:immunology; D007422:Intestines / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D007583:Jejunum / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008297:Male; D044342:Malnutrition; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000187:drug effects / Q000382:microbiology; D014131:Trace Elements / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000276:immunology; D015430:Weight Gain / Q000187:drug effects; D015032:Zinc / Q000494:pharmacology*
chemical_list: C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D014131:Trace Elements; D014409:Tumor Necrosis Factor-alpha; D015032:Zinc
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