Abstract
BACKGROUND: Zinc has been shown to have beneficial effects in vitro on epithelial barrier function, and in vivo to reduce intestinal permeability in malnourished children with diarrhoea. AIMS: To determine whether malnutrition alters intestinal paracellular permeability, and whether zinc prevents such alterations. METHODS: Guinea pigs were fed a normal protein diet (NP group), a low protein diet (LP group), or a low protein diet enriched with 1800 ppm zinc (LPZn group) for three weeks. Intestinal permeability was measured on jejunal segments mounted in Ussing chambers by measuring ionic conductance and mucosal to serosal fluxes of 14C-mannitol, 22Na, and horseradish peroxidase. Tight junction morphology was assessed on cryofracture replicas. RESULTS: Mannitol and Na fluxes and ionic conductance increased in the LP group compared with the NP group but remained normal in the LPZn group. Accordingly, jejunal epithelia from the LP group, but not from the LPZn group, showed a small decrease in number of tight junctional strands compared with epithelia from the NP group. Neither malnutrition nor zinc treatment modified horseradish peroxidase fluxes. CONCLUSIONS: Malnutrition is associated with increased intestinal paracellular permeability to small molecules, and pharmacological doses of zinc prevent such functional abnormality.
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- Alam A. N., Sarker S. A., Wahed M. A., Khatun M., Rahaman M. M. Enteric protein loss and intestinal permeability changes in children during acute shigellosis and after recovery: effect of zinc supplementation. Gut. 1994 Dec;35(12):1707–1711. doi: 10.1136/gut.35.12.1707. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Butzner J. D., Brockway P. D., Meddings J. B. Effects of malnutrition on microvillus membrane glucose transport and physical properties. Am J Physiol. 1990 Dec;259(6 Pt 1):G940–G946. doi: 10.1152/ajpgi.1990.259.6.G940. [DOI] [PubMed] [Google Scholar]
- Carey H. V., Hayden U. L., Tucker K. E. Fasting alters basal and stimulated ion transport in piglet jejunum. Am J Physiol. 1994 Jul;267(1 Pt 2):R156–R163. doi: 10.1152/ajpregu.1994.267.1.R156. [DOI] [PubMed] [Google Scholar]
- Darmon N., Pélissier M. A., Heyman M., Albrecht R., Desjeux J. F. Oxidative stress may contribute to the intestinal dysfunction of weanling rats fed a low protein diet. J Nutr. 1993 Jun;123(6):1068–1075. doi: 10.1093/jn/123.6.1068. [DOI] [PubMed] [Google Scholar]
- Decker Butzner J., Grant Gall D. Impact of protein-calorie malnutrition on the developing intestine. A model in young rabbits. Biol Neonate. 1988;54(3):151–159. doi: 10.1159/000242846. [DOI] [PubMed] [Google Scholar]
- Elmes M. E., Jones J. G. Ultrastructural changes in the small intestine of zinc deficient rats. J Pathol. 1980 Jan;130(1):37–43. doi: 10.1002/path.1711300106. [DOI] [PubMed] [Google Scholar]
- Ghishan F. K. Transport of electrolytes, water, and glucose in zinc deficiency. J Pediatr Gastroenterol Nutr. 1984 Sep;3(4):608–612. doi: 10.1097/00005176-198409000-00022. [DOI] [PubMed] [Google Scholar]
- Gonzalez-Mariscal L., Contreras R. G., Bolívar J. J., Ponce A., Chávez De Ramirez B., Cereijido M. Role of calcium in tight junction formation between epithelial cells. Am J Physiol. 1990 Dec;259(6 Pt 1):C978–C986. doi: 10.1152/ajpcell.1990.259.6.C978. [DOI] [PubMed] [Google Scholar]
- Hennig B., Wang Y., Ramasamy S., McClain C. J. Zinc deficiency alters barrier function of cultured porcine endothelial cells. J Nutr. 1992 Jun;122(6):1242–1247. doi: 10.1093/jn/122.6.1242. [DOI] [PubMed] [Google Scholar]
- Hennig B., Wang Y., Ramasamy S., McClain C. J. Zinc protects against tumor necrosis factor-induced disruption of porcine endothelial cell monolayer integrity. J Nutr. 1993 Jun;123(6):1003–1009. doi: 10.1093/jn/123.6.1003. [DOI] [PubMed] [Google Scholar]
- Heyman M., Boudraa G., Sarrut S., Giraud M., Evans L., Touhami M., Desjeux J. F. Macromolecular transport in jejunal mucosa of children with severe malnutrition: a quantitative study. J Pediatr Gastroenterol Nutr. 1984 Jun;3(3):357–363. doi: 10.1097/00005176-198406000-00009. [DOI] [PubMed] [Google Scholar]
- Lamont A. G., Gordon M., Ferguson A. Oral tolerance in protein-deprived mice. II. Evidence of normal 'gut processing' of ovalbumin, but suppressor cell deficiency, in deprived mice. Immunology. 1987 Jul;61(3):339–343. [PMC free article] [PubMed] [Google Scholar]
- MAEHLY A. C., CHANCE B. The assay of catalases and peroxidases. Methods Biochem Anal. 1954;1:357–424. doi: 10.1002/9780470110171.ch14. [DOI] [PubMed] [Google Scholar]
- Madara J. L., Barenberg D., Carlson S. Effects of cytochalasin D on occluding junctions of intestinal absorptive cells: further evidence that the cytoskeleton may influence paracellular permeability and junctional charge selectivity. J Cell Biol. 1986 Jun;102(6):2125–2136. doi: 10.1083/jcb.102.6.2125. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Madara J. L., Pappenheimer J. R. Structural basis for physiological regulation of paracellular pathways in intestinal epithelia. J Membr Biol. 1987;100(2):149–164. doi: 10.1007/BF02209147. [DOI] [PubMed] [Google Scholar]
- Madara J. L., Stafford J., Barenberg D., Carlson S. Functional coupling of tight junctions and microfilaments in T84 monolayers. Am J Physiol. 1988 Mar;254(3 Pt 1):G416–G423. doi: 10.1152/ajpgi.1988.254.3.G416. [DOI] [PubMed] [Google Scholar]
- Madara J. L., Stafford J. Interferon-gamma directly affects barrier function of cultured intestinal epithelial monolayers. J Clin Invest. 1989 Feb;83(2):724–727. doi: 10.1172/JCI113938. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marcial M. A., Carlson S. L., Madara J. L. Partitioning of paracellular conductance along the ileal crypt-villus axis: a hypothesis based on structural analysis with detailed consideration of tight junction structure-function relationships. J Membr Biol. 1984;80(1):59–70. doi: 10.1007/BF01868690. [DOI] [PubMed] [Google Scholar]
- McCance R. A., Widdowson E. M. Protein deficiencies and calorie deficiencies. Lancet. 1966 Jul 16;2(7455):158–159. doi: 10.1016/s0140-6736(66)92439-1. [DOI] [PubMed] [Google Scholar]
- Moran J. R., Lewis J. C. The effects of severe zinc deficiency on intestinal permeability: an ultrastructural study. Pediatr Res. 1985 Sep;19(9):968–973. doi: 10.1203/00006450-198509000-00020. [DOI] [PubMed] [Google Scholar]
- Nash S., Stafford J., Madara J. L. The selective and superoxide-independent disruption of intestinal epithelial tight junctions during leukocyte transmigration. Lab Invest. 1988 Oct;59(4):531–537. [PubMed] [Google Scholar]
- Powell D. W. Barrier function of epithelia. Am J Physiol. 1981 Oct;241(4):G275–G288. doi: 10.1152/ajpgi.1981.241.4.G275. [DOI] [PubMed] [Google Scholar]
- Rodriguez P., Heyman M., Candalh C., Blaton M. A., Bouchaud C. Tumour necrosis factor-alpha induces morphological and functional alterations of intestinal HT29 cl.19A cell monolayers. Cytokine. 1995 Jul;7(5):441–448. doi: 10.1006/cyto.1995.0060. [DOI] [PubMed] [Google Scholar]
- Roy S. K., Behrens R. H., Haider R., Akramuzzaman S. M., Mahalanabis D., Wahed M. A., Tomkins A. M. Impact of zinc supplementation on intestinal permeability in Bangladeshi children with acute diarrhoea and persistent diarrhoea syndrome. J Pediatr Gastroenterol Nutr. 1992 Oct;15(3):289–296. doi: 10.1097/00005176-199210000-00010. [DOI] [PubMed] [Google Scholar]
- Sazawal S., Black R. E., Bhan M. K., Bhandari N., Sinha A., Jalla S. Zinc supplementation in young children with acute diarrhea in India. N Engl J Med. 1995 Sep 28;333(13):839–844. doi: 10.1056/NEJM199509283331304. [DOI] [PubMed] [Google Scholar]
- Serrano L., Dominguez J. E., Avila J. Identification of zinc-binding sites of proteins: zinc binds to the amino-terminal region of tubulin. Anal Biochem. 1988 Jul;172(1):210–218. doi: 10.1016/0003-2697(88)90434-4. [DOI] [PubMed] [Google Scholar]
- Shay N. F., Cousins R. J. Cloning of rat intestinal mRNAs affected by zinc deficiency. J Nutr. 1993 Jan;123(1):35–41. doi: 10.1093/jn/123.1.35. [DOI] [PubMed] [Google Scholar]
- Strzelecka-Gołaszewska H., Pròchniewicz E., Drabikowski W. Interaction of actin with divalent cations. 1. The effect of various cations on the physical state of actin. Eur J Biochem. 1978 Jul 17;88(1):219–227. doi: 10.1111/j.1432-1033.1978.tb12441.x. [DOI] [PubMed] [Google Scholar]
- Tacnet F., Ripoche P., Roux M., Neumann J. M. 31P-NMR study of pig intestinal brush-border membrane structure: effect of zinc and cadmium ions. Eur Biophys J. 1991;19(6):317–322. doi: 10.1007/BF00183321. [DOI] [PubMed] [Google Scholar]
- Walsh C. T., Sandstead H. H., Prasad A. S., Newberne P. M., Fraker P. J. Zinc: health effects and research priorities for the 1990s. Environ Health Perspect. 1994 Jun;102 (Suppl 2):5–46. doi: 10.1289/ehp.941025. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Worthington B. S., Syrotuck J. Intestinal permeability to large particles in normal and protein-deficient adult rats. J Nutr. 1976 Jan;106(1):20–32. doi: 10.1093/jn/106.1.20. [DOI] [PubMed] [Google Scholar]
- Young A., Levin R. J. Diarrhoea of famine and malnutrition: investigations using a rat model. 1. Jejunal hypersecretion induced by starvation. Gut. 1990 Jan;31(1):43–53. doi: 10.1136/gut.31.1.43. [DOI] [PMC free article] [PubMed] [Google Scholar]