Methods and options for estimating iron and zinc bioavailability using Caco-2 cell models: Benefits and limitations

International Journal for Vitamin and Nutrition Research

Volumn 75, Issue 6, 2005, Pages 413-421

  Sharp, Paul ^a  

^a KING'S COLLEGE LONDON   (United Kingdom)

Author keywords

Bioavailability; Caco 2 cells; Human; Intestine; Iron; Zinc

Indexed keywords

BIOLOGICAL MARKER; IRON; PLASTIC; TRACE ELEMENT; ZINC;

BIOAVAILABILITY; CELL DIFFERENTIATION; CELL STRAIN CACO 2; CELL TYPE; DIGESTION; FOOD INTAKE; HUMAN; IN VITRO STUDY; INTESTINE EPITHELIUM; IRON ABSORPTION; IRON TRANSPORT; ISOTOPE TRACING; NONHUMAN; REVIEW;

BIOLOGICAL AVAILABILITY; CACO-2 CELLS; HUMANS; INTESTINAL ABSORPTION; IRON; ZINC;

EID: 33646257081     PISSN: 03009831     EISSN: None     Source Type: Journal    
DOI: 10.1024/0300-9831.75.6.413     Document Type: Review

References (80)

1. nd ed. World Health Organization, Geneva. Switzerland. (WHO/MCH /MSM/92.2.).
2. Stoltzfus, R. J. (2001) Defining iron-deficiency anemia in public health terms: a time for reflection. J. Nutr. 131, 565S-567S.
3. Hotz, C. and Brown, K. H. (2001) Identifying populations at risk of zinc deficiency: the use of supplementation trials. Nutr. Rev. 59, 80-84.
4. Sandstead, H. H. (1996) Zinc deficiency: a public health problem? Am. J. Dis. Child. 145, 853-859.
5. World Health Organization. (1995) Global prevalence of vitamin A deficiency. Micronutrient Deficiency Information System. MDIS Working Paper 2. World Health Organization. Geneva. Switzerland. (WHO/NUT/95.3).
6. Underwood. B. A. (2004) Vitamin A deficiency disorders: international efforts to control a preventable "pox". J. Nutr. 134, 231S-236S.
7. Fogh, J., Fogh, J.M. and Orfeo, T. (1977) One hundred and twenty-seven cultured human tumor cell lines producing tumors in nude mice. J. Natl. Cancer Inst. 59, 221-226.
8. Chantret, I., Barbat, A., Dussaulx, E., Brattain, M. G. and Zweibaum, A. (1988) Epithelial polarity, villin expression, and enterocytic differentiation of cultured human colon carcinoma cells: a survey of twenty cell lines. Cancer Res. 48. 1936-1942.
9. Chantret, I., Rodolosse, A., Barbat, A., Dussaulx, E., Brot-Laroche, E., Zweibaum, A. and Rousset, M. (1994) Differential expression of sucrase-isomaltase in clones isolated from early and late passages of the cell line Caco-2: evidence for glucose-dependent negative regulation. J. Cell Sci. 107, 213-225.
10. Bissonnette, P., Gagne, H., Coady, M.J., Benabdallah, K., Lapointe, J. Y. and Berteloot, A. (1996) Kinetic separation and characterization of three sugar transport modes in Caco-2 cells. Am. J. Physiol. 270, G833-G843.
11. Mahraoui, L., Takeda, J., Mesonero, J., Chantret, I., Dussaulx, E., Bell, G. I. and Brot-Laroche, E. (1994) Regulation of expression of the human fructose transporter (GLUT5) by cyclic AMP. Biochem. J. 301, 169-175.
12. Erickson, R. H., Gum, J. R. Jr., Lindstrom, M. M., McKean, D. and Kim, Y. S. (1995) Regional expression and dietary regulation of rat small intestinal peptide and amino acid transporter mRNAs. Biochem. Biophys. Res. Commun. 216, 249-257.
13. Tandy, S., Williams, M., Leggett, A., Lopez-Jimenez, M., Dedes, M., Ramesh, B., Srai, S. K. and Sharp, P. (2000) Nramp2 expression is associated with pH-dependent iron uptake across the apical membrane of human intestinal Caco-2 cells. J. Biol. Chem. 275, 1023-1029.
14. Cragg, R. A., Christie, G. R., Phillips, S. R., Russi, R. M., Kury, S., Mathers, J. C., Taylor, P. M. and Ford, D. (2002) A novel zinc-regulated human zinc transporter, hZTL1, is localized to the enterocyte apical membrane. J. Biol. Chem. 277, 22789-22797.
15. Alvarez-Hernandez, X., Nichols, G. M. and Glass, J. (1991) Caco-2 cell line: a system for studying intestinal iron transport across epithelial cell monolayers. Biochim. Biophys. Acta. 1070, 205-208.
16. Bates, C. J. (1997) Bioavailability of vitamin C. Eur. J. Clin. Nutr 51, S28-S33.
17. Albers, T. M., Lomakina, I. and Moore, R. P. (1995) Fate of polarized membrane components and evidence for microvillus disassembly on migrating enterocytes during repair of native intestinal epithelium. Lab. Invest. 73, 139-148.
18. Chew, C. S., Safsten, B. and Flemstrom, G. (1998) Calcium signalling in cultured human and rat duodenal enterocytes. Am. J. Physiol. 275, G296-G304.
19. Hunt, J. Internat. J. Vit. Nutr. Res. this volume.
20. Hambidge, M. Internat. J. Vit. Nutr. Res. this volume
21. Ekmekcioglu, C., Feyertag, J. and Marktl, W. (1996) A ferric reductase activity is found in brush border membrane vesicles isolated from Caco-2 cells. J. Nutr. 126, 2209-2217.
22. Han, O., Failla, M. L., Hill, A. D., Morris, E. R., and Smith, J. C. Jr. (1995) Reduction of Fe(III) is required for uptake of nonheme iron by Caco-2 cells. J. Nutr. 125, 1291-1299.
23. Han, O. and Wessling-Resnick, M. (2002) Copper repletion enhances apical iron uptake and transepithelial iron transport by Caco-2 cells. Am. J. Physiol. 282, G527-G533.
24. Yamaji, S., Tennant, J., Tandy, S., Williams, M., Srai, S. K. S. and Sharp, P. (2001) Zinc regulates the function and expression of the iron transporters DMT1 and IREG1 in human intestinal Caco-2 cells. FEBS Lett. 507, 137-141.
25. Tennant, J., Stansfield, M., Yamaji, S., Srai, S. K. and Sharp, P. (2002) Effects of copper on the expression of metal transporters in human intestinal Caco-2 cells. FEBS Lett. 527, 239-244.
26. Linder, M. C., Zerounian, N. R., Moriya, M. and Malpe, R. (2003) Iron and copper homeostasis and intestinal absorption using the Caco-2 cell model. Biometals 16, 145-160.
27. Ford, D. (2004) Intestinal and placental zinc transport pathways. Proc. Nutr. Soc. 63, 21-29.
28. Flier, J. S., Mueckler, M. M., Usher, P. and Lodish, H. F. (1987) Elevated levels of glucose transport and transporter messenger RNA are induced by ras or src oncogenes. Science 235, 1492-1495.
29. Birnbaum, M. J., Haspel, H. C. and Rosen, O. M. (1987) Transformation of rat fibroblasts by FSV rapidly increases glucose transporter gene transcription. Science 235, 1495-1498.
30. Yamamoto, T., Seino, Y., Fukumoto, H., Koh, G., Yano, H., Inagaki, N., Yamada, Y., Inoue, K., Manabe, T. and Imura, H. (1990) Over-expression of facilitative glucose transporter genes in human cancer. Biochem. Biophys. Res. Commun. 170, 223-230.
31. Harris, D. S., Slot, J. W., Geuze, H. J. and James, D. E. (1992) Polarized distribution of glucose transporter isoforms in Caco-2 cells. Proc. Natl. Acad. Sci. U.S.A. 89, 7556-7560.
32. Mahraoui, L., Rodolosse, A., Barbat, A., Dussaulx, E., Zweibaum, A., Roussel, M. and Brot-Laroche, E. (1994) Presence and differential expression of SGLT1, GLUT1, GLUT2, GLUT3 and GLUT5 hexose-transporter mRNAs in Caco-2 cell clones in relation to cell growth and glucose consumption. Biochem. J. 298, 629-633.
33. Han, O., Fleet, J. C. and Wood, R. J. (1999) Reciprocal regulation of HFE and NNamp2 gene expression by iron in human intestinal cells. J. Nutr. 129, 98-104.
34. Sharp, P. A., Tandy, S. R., Yamaji, S., Tennant, J. P., Williams, M. R. and Srai, S. K. S. (2002) Rapid regulation of Divalent Metal Transporter (DMT1) protein but not mRNA expression by non-haem iron in human intestinal Caco-2 cells. FEBS Lett. 510, 71-76.
35. Glahn, R. P. and Van Campen, D. R. (1997) Iron uptake is enhanced in Caco-2 cell monolayers by cysteine and reduced cysteinyl glycine. J. Nutr. 127, 642-647.
36. Garcia-Casal, M. N., Leets, I. and Layrisse, M. (2000) β-carotene and inhibitors of iron absorption modify iron uptake by Caco-2 cells. J. Nutr. 130, 5-9.
37. Han, O., Failla, M. L., Hill, A. D., Morris, E. R. and Smith, J. C. Jr. (1994) Inositol phosphates inhibit uptake and transport of iron and zinc by a human intestinal cell line. J. Nutr. 124, 580-587.
38. Han, O., Failla, M. L., Hill, A. D., Morris, E. R. and Smith, J. C. Jr. (1995) Ascorbate offsets the inhibitory effect of inositol phosphates on iron uptake and transport by Caco-2 cells. Proc. Soc. Exp. Biol. Med. 210, 50-56.
39. Moltedo, O., Verde, C., Capasso, A., Parisi, E., Remondelli, P., Bonatti, S., Alvarez-Hernandez, X., Glass, J., Alvino, C. G. and Leone, A. (2000) Zinc transport and metallothionein secretion in the intestinal human cell line Caco-2. J. Biol. Chem. 275, 31819-31825.
40. Navarro, P., Aspe, T. and Seiquer, I. (2000) Zinc transport in Caco-2 cells and zinc balance in rats: influence of the heat treatment of a casein-glucose-fructose mixture. J. Agric. Food Chem. 48, 3589-3596.
41. Tallkvist, J., Bowlus, C. L. and Lonnerdal, B. (2000) Functional and molecular responses of human intestinal Caco-2 cells to iron treatment. Am. J. Clin. Nutr. 72, 770-775.
42. Reeves, P. G., Briske-Anderson, M. and Johnson, L. (2001) Pre-treatment of Caco-2 cells with zinc during the differentiation phase alters the kinetics of zinc uptake and transport. J. Nutr. Biochem. 12, 674-684.
43. Alvarez-Hernandez, X., Smith, M. and Glass, J. (1998) The effect of apotransferrin on iron release from Caco-2 cells, an intestinal epithelial cell line. Blood 91, 3974-3979.
44. Nunez, M. T. and Tapia, V. (1999) Transferrin stimulates iron absorption, exocytosis, and secretion in cultured intestinal cells. Am. J. Physiol. 276, C1085-C1090.
45. Tandy, S., Moody, N., Williams, M., Srai, S. K. and Sharp, P. (2001) Basolateral iron supplementation results in reduced DMT-1-mediated iron uptake by human intestinal Caco-2 cells. J. Physiol. 531P, 127P.
46. Yamaji, S., Sharp, P., Ramesh, B. and Srai S.K. (2004) Inhibition of iron transport across human intestinal epithelial cells by hepcidin. Blood 104, 2178-2180.
47. Johnson, D. M., Bayele, H., Johnston, K.L., Tennant, J.P., Srai, S. K. S. and Sharp P. A. (2004) The role of Tumour Necrosis Factor alpha in regulating iron transport across human intestinal epithelial cells. FEBS Lett. 573, 195-201.
48. Garcia, M. N., Flowers, C. and Cook, J. D. (1996) The Caco-2 cell culture system can be used as a model to study food iron availability. J. Nutr. 126, 51-58.
49. Glahn, R. P., Wien, E. M., Van Campen, D. R. and Miller, D. D. (1996) Caco-2 cell iron uptake from meat and casein digests parallels in vivo studies: use of a novel in vitro method for rapid estimation of iron bioavailability. J. Nutr. 126, 332-339.
50. Glahn, R. P., Lai, C., Hsu, J., Thompson, J. F., Guo, M. and Van Campen, D. R. (1998) Decreased citrate improves iron availability from infant formula: application of an in vitro digestion/Caco-2 cell culture model. J. Nutr. 128, 257-264.
51. Glahn, R. P., Lee, O. A., Yeung, A., Goldman, M. I. and Miller, D. D. (1998) Caco-2 cell ferritin formation predicts nonradiolabeled food iron availability in an in vitro digestion/Caco-2 cell culture model. J. Nutr. 128, 1555-1561.
52. Au, A. P. and Reddy, M. B. (2000) Caco-2 cells can be used to assess human iron bioavailability from a semipurified meal. J. Nutr. 130, 1329-1339.
53. Seiquer, I., Valverde, A., Delgado-Andrade, C. and Navarro, M. P. (2000) Influence of heat treatment of casein in presence of reducing sugars on Zn solubility and Zn uptake by Caco-2 cells after in vitro digestion. J. Physiol. Biochem. 56, 237-246.
54. Puyfoulhoux, G., Rouanet, J. M., Besancon, P., Baroux, B., Baccou, J. C. and Caporiccio, B. (2001) Iron availability from iron-fortified spirulina by an in vitro digestion/Caco-2 cell culture model. J. Agric. Food Chem. 49, 1625-1629.
55. Glahn, R. P., Wortley, G. M., South, P. K. and Miller, D. D. (2002) Inhibition of iron uptake by phytic acid, tannic acid, and ZnCl2: studies using an in vitro digestion/Caco-2 cell model. J. Agric. Food Chem. 50, 390-395.
56. Glahn, R. P., Cheng, Z., Welch, R. M. and Gregorio, G. B. (2002) Comparison of iron bioavailability from 15 rice genotypes: studies using an in vitro digestion/caco-2 cell culture model. J. Agric. Food Chem. 50, 3586-3591.
57. Swain, J. H., Tabatabai, L. B. and Reddy, M. B. (2002) Histidine content of low-molecular-weight beef proteins influences nonheme iron bioavailability in Caco-2 cells. J. Nutr. 132, 245-251.
58. Boato, F., Wortley, G. M., Liu, R. H. and Glahn, R. P. (2002) Red grape juice inhibits iron availability: application of an in vitro digestion/Caco-2 cell model. J. Agric. Food Chem. 50, 6935-6938.
59. Serfass, R. E. and Reddy, M. B. (2003) Breast milk fractions solubilize Fe(III) and enhance iron flux across Caco-2 cells. J. Nutr. 133, 449-455.
60. Oikeh, S. O., Menkir, A., Maziya-Dixon, B., Welch, R. and Glahn, R. P. (2003) Assessment of concentrations of iron and zinc and bioavailable iron in grains of early-maturing tropical maize varieties. J. Agric. Food Chem. 51, 3688-3694.
61. Etcheverry, P., Miller, D. D. and Glahn, R. P. (2004) A low-molecular-weight factor in human milk whey promotes iron uptake by Caco-2 cells. J. Nutr. 134, 93-98.
62. Etcheverry, P., Wallingford, J. C., Miller, D. D. and Glahn, R. P. (2004) Calcium, zinc, and iron bioavailabilities from a commercial human milk fortifier: a comparison study. J. Dairy Sci. 87, 3629-3637.
63. Huh, E. G., Hotchkiss, A., Brouillette, J. and Glahn, R. P. (2004) Carbohydrate fractions from cooked fish promote iron uptake by Caco-2 cells. J. Nutr. 134, 1681-1689.
64. Yun, S., Habicht, J. P., Miller, D. D. and Glahn, R. P. (2004) An in vitro digestion/Caco-2 cell culture system accurately predicts the effects of ascorbic acid and polyphenolic compounds on iron bioavailability in humans. J. Nutr. 134, 2717-2721.
65. Delie, F. and Rubas, W. (1997) A human colonic cell line sharing similarities with enterocytes as a model to examine oral absorption: advantages and limitations of the Caco-2 model. Crit. Rev. Ther. Drug Carrier Syst. 14, 221-286.
66. Johnson, D., Tennant, J. and Sharp, P. (2003) DMT1 protein expression in the apical membrane of human intestinal Caco-2 cells is rapidly decreased following exposure to iron. J. Physiol. 549P, 11P.
67. Yeh, K. Y., Yeh, M., Watkins, J. A., Rodriguez-Paris, J. and Glass, J. (2000) Dietary iron induces rapid changes in rat intestinal divalent metal transporter expression. Am. J. Physiol. 279, G1070-G1079.
68. Frazer, D. M., Wilkins, S. J., Becker, E. M., Murphy, T. L., Vulpe, C. D., McKie, A. T. and Anderson, G. J. (2003) A rapid decrease in the expression of DMT1 and Dcytb but not Ireg1 or hephaestin explains the mucosal block phenomenon of iron absorption. Gut 52, 340-346.
69. Poskitt, E. M. (2003) Early history of iron deficiency. Br. J. Haematol. 122, 554-562.
70. Sharma, V. R., Brannon, M. A. and Carloss, E. A. (2004) Effect of omeprazole on oral iron replacement in patients with iron deficiency anemia. South. Med. J. 97, 887-889.
71. Gunshin, H., Mackenzie, B., Berger, U. V., Gunshin, Y., Romero, M. F., Boron, W. F., Nussberger, S., Gollan, J. L. and Hediger, M. A. (1997) Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature 388, 482-488.
72. Ashida, K., Sasaki, H., Suzuki, Y. A. and Lonnerdal, B. (2004) Cellular internalization of lactoferrin in intestinal epithelial cells. Biometals 17, 311-315.
73. Davila-Hicks, P., Theil, E. C. and Lonnerdal, B. (2004) Iron in ferritin or in salts (ferrous sulfate) is equally bioavailable in nonanemic women. Am. J. Clin. Nutr. 80, 936-940.
74. Miller, D. D., Schricker, B. R., Rasmussen, R. R. and Van Campen, D. (1981) An in vitro method for estimation of iron availability from meals. Am. J. Clin. Nutr. 34, 2248-2256.
75. Zweibaum, A., Triadou, N., Kedinger, M., Augeron, C., Robine-Leon, S., Pinto, M., Roussel, M. and Haffen, K. (1983) Sucrase-isomaltase: a marker of foetal and malignant epithelial cells of the human colon. Int. J. Cancer. 32, 407-412.
76. Walker, D., Thwaites, D. T., Simmons, N. L., Gilbert, H. J. and Hirst, B. H. (1998) Substrate upregulation of the human small intestinal peptide transporter, hPepT1. J. Physiol. 507, 697-706.
77. O'Riordan, D. K., Sharp, P., Sykes, R. M., Srai, S. K., Epstein, O. and Debnam, E. S. (1995) Cellular mechanisms underlying the increased duodenal iron absorption in rats in response to phenylhydrazine-induced haemolytic anaemia. Eur. J. Clin. Invest. 25, 722-727.
78. O'Riordan, D. K., Debnam, E. S., Sharp, P. A., Simpson, R. J., Taylor, E. M. and Srai, S. K. (1997) Mechanisms involved in increased iron uptake across rat duodenal brush-border membrane during hypoxia. J. Physiol. 500, 379-384.
79. Smith, M. W., Debnam, E. S., Dashwood, M. R. and Srai, S. K. (2000) Structural and cellular adaptation of duodenal iron uptake in rats maintained on an iron-deficient diet. Pflügers Arch. 439, 449-454.
80. Dorey, C., Cooper, C., Dickson, D. P., Gibson, J. F., Simpson, R. J. and Peters, T. J. (1993) Iron speciation at physiological pH in media containing ascorbate and oxygen. Br. J. Nutr. 70, 157-169.