Food additive carrageenan: Part I: A critical review of carrageenan in vitro studies, potential pitfalls, and implications for human health and safety

References

• Abreu MT, Arnold ET, Thomas LS, et al. (2002). TLR4 and MD-2 expression is regulated by immune-mediated signals in human intestinal epithelial cells. J Biol Chem, 277, 20431–7
   PubMed Web of Science ®Google Scholar
• Abreu MT, Thomas LS, Arnold ET, et al. (2003). TLR signaling at the intestinal epithelial interface. J Endotoxin Res, 9, 322–30
   PubMedGoogle Scholar
• Abreu MT, Vora P, Faure E, et al. (2001). Decreased expression of toll-like receptor-4 and MD-2 correlates with intestinal epithelial cell protection against dysregulated proinflammatory gene expression in response to bacterial lipopolysaccharide. J Immunol, 167, 1609–16
   PubMed Web of Science ®Google Scholar
• Andrikopoulos S, Blair AR, Deluca N, et al. (2008). Evaluating the glucose tolerance test in mice. Am J Physiol Endocrinol Metab, 295, E1323–32
   PubMed Web of Science ®Google Scholar
• Arakawa S, Ito M, Tejima S. (1988). Promoter function of carrageenan on development of colonic tumors induced by 1,2-dimethylhydrazine in rats. J Nutr Sci Vitaminol, 34, 577–85
   PubMed Web of Science ®Google Scholar
• Araki Y, Sugihara H, Hattori T. (2006). In vitro effects of dextran sulfate sodium on a caco-2 cell line and plausible mechanisms for dextran sulfate sodium-induced colitis. Oncol Rep, 16, 1357–62
   PubMedGoogle Scholar
• Bachmanov AA, Reed DR, Beauchamp GK, Tordoff MG. (2002). Food intake, water intake, and drinking spout side preference of 28 mouse strains. Behav Genet, 32, 435–43
   PubMed Web of Science ®Google Scholar
• Bai J, Cederbaum AI. (2006). Cycloheximide protects HepG2 cells from serum withdrawal-induced apoptosis by decreasing p53 and phosphorylated p53 levels. J Pharmacol Exp Therap, 319, 1435–43
   PubMed Web of Science ®Google Scholar
• Barthe L, Woodley J, Lavit M, et al. (2004). In vitro intestinal degradation and absorption of chondroitin sulfate, a glycosaminoglycan drug. Arzneimittelforschung, 54, 286–92
   PubMed Web of Science ®Google Scholar
• Benard C, Cultrone A, Michel C, et al. (2010). Degraded carrageenan causing colitis in rats induces TNF secretion and ICAM-1 upregulation in monocytes through NF-kappaB activation. PLoS One, 5, e8666
   PubMed Web of Science ®Google Scholar
• Bhattacharyya S, Borthakur A, Anbazhagan AN, et al. (2011). Specific effects of BCL10 serine mutations on phosphorylations in canonical and noncanonical pathways of NF-κB activation following carrageenan. Am J Physiol Gastrointest Liver Physiol, 301, G475–86
   PubMed Web of Science ®Google Scholar
• Bhattacharyya S, Borthakur A, Dudeja PK, Tobacman JK. (2007). Carrageenan reduces bone morphogenetic protein-4 (BMP4) and activates the Wnt/beta-catenin pathway in normal human colonocytes. Dig Dis Sci, 52, 2766–74
   PubMed Web of Science ®Google Scholar
• Bhattacharyya S, Borthakur A, Dudeja PK, Tobacman JK. (2008a). Carrageenan induces cell cycle arrest in human intestinal epithelial cells in vitro. J Nutr, 138, 469–75
   PubMed Web of Science ®Google Scholar
• Bhattacharyya S, Borthakur A, Tyagi S, et al. (2010b). B-cell CLL/lymphoma 10 (BCL10) is required for NF-kappaB production by both canonical and noncanonical pathways and for NF-kappaB-inducing kinase (NIK) phosphorylation. J Biol Chem, 285, 522–30
   PubMed Web of Science ®Google Scholar
• Bhattacharyya S, Dudeja PK, Tobacman JK. (2008b). Carrageenan-induced NF-kappaB activation depends on distinct pathways mediated by reactive oxygen species and Hsp27 or by Bcl10. Biochim Biophys Acta, 1780, 973–82
   PubMed Web of Science ®Google Scholar
• Bhattacharyya S, Gill R, Chen ML, et al. (2008c). Toll-like receptor 4 mediates induction of the Bcl10–NF–kappaB–interleukin-8 inflammatory pathway by carrageenan in human intestinal epithelial cells. J Biol Chem, 283, 10550–8
   PubMed Web of Science ®Google Scholar
• Bhattacharyya S, Liu H, Zhang Z, et al. (2010a). Carrageenan-induced innate immune response is modified by enzymes that hydrolyze distinct galactosidic bonds. J Nutr Biochem, 21, 906–13
   PubMed Web of Science ®Google Scholar
• Bhattacharyya S, O-Sullivan I, Katyal S, et al. (2012). Exposure to the common food additive carrageenan leads to glucose intolerance, insulin resistance and inhibition of insulin signaling in HepG2 cells and C57BL/6J mice. Diabetologia, 55, 194–203
   PubMed Web of Science ®Google Scholar
• Bhattacharyya S, Solakyildirim K, Zhang Z, et al. (2010c). Cell-bound IL-8 increases in bronchial epithelial cells after arylsulfatase B silencing due to sequestration with chondroitin-4-sulfate. Am J Respir Cell Mol Bio, 42, 51–61
   PubMedGoogle Scholar
• Bhattacharyya S, Tobacman JK. (2007). Steroid sulfatase, arylsulfatases A and B, galactose-6-sulfatase, and iduronate sulfatase in mammary cells and effects of sulfated and non-sulfated estrogens on sulfatase activity. J Steroid Biochem Mol Biol, 103, 20–34
   PubMedGoogle Scholar
• Bhattacharyya S, Tobacman JK. (2012). Molecular signature of kappa-carrageenan mimics chondroitin-4-sulfate and dermatan sulfate and enables interaction with arylsulfatase B. J Nutr Biochem, 23, 1058--63
   Google Scholar
• Blakemore WR, Harpell AR. (2010). Carrageenan. In: Alan Imeson, ed. Food stabilizers, thickeners and gelling agent. Chapter 5. Wiley-Blackwell, Blackwell Publishing Ltd. Published online, 73--94
   Google Scholar
• Borthakur A, Bhattacharyya S, Anbazhagan AN, et al. (2012). Prolongation of carrageenan-induced inflammation in human colonic epithelial cells by activation of an NF-κB-BCL10 loop. Biochem Biophys Acta, 1822, 1300–7
   PubMed Web of Science ®Google Scholar
• Borthakur A, Bhattacharyya S, Dudeja PK, Tobacman JK. (2007). Carrageenan induces interleukin-8 production through distinct Bcl10 pathway in normal human colonic epithelial cells. Am J Physiol Gastrointest Liver Physiol, 292, G829–38
   PubMed Web of Science ®Google Scholar
• Brenchley JM, Douek DC. (2008). HIV infection and the gastrointestinal immune system. Mucosal Immunol, 1, 23–30
   PubMed Web of Science ®Google Scholar
• Calvert RJ, Reicks M. (1988). Alterations in colonic thymidine kinase enzyme activity induced by consumption of various dietary fibers. Proc Soc Exp Biol Med, 189, 45–51
   PubMed Web of Science ®Google Scholar
• Calvert RJ, Satchithanandam S. (1992). Effects of graded levels of high-molecular-weight carrageenan on colonic mucosal thymidine kinase activity. Nutrition, 8, 252–7
   PubMedGoogle Scholar
• Capron I, Yvon M, Muller G. (1996). In vitro gastric stability of carrageenan. Food Hydocolloids, 10, 239–44
   Web of Science ®Google Scholar
• Cario E, Podolsky DK. (2000). Differential alteration in intestinal epithelial cell expression of toll-like receptor 3 (TLR3) and TLR4 in inflammatory bowel disease. Infect Immun, 68, 7010–7
   PubMed Web of Science ®Google Scholar
• Cohen S, Ito N. (2002). A critical review of the toxicological effects of carrageenan and processed eucheuma seaweed on the gastrointestinal tract. Crit Rev Toxicol, 32, 413–44
   PubMed Web of Science ®Google Scholar
• Conte A, Volpi N, Palmieri L, et al. (1995). Biochemical and pharmacokinetic aspects of oral treatment with chondroitin sulfate. Arzneimittelforschung, 45, 618–25
   Google Scholar
• Creamer B. (1967). The turnover of the epithelium of the small intestine. Br Med Bull, 23, 226–30
   PubMed Web of Science ®Google Scholar
• DeFronzo RA, Bonadonna RC, Ferrannini E. (1992). Pathogenesis of NIDDM. Diabetes Care, 15, 318–68
   PubMed Web of Science ®Google Scholar
• DeSesso JM, Jacobson CF. (2001). Anatomical and physiological parameters affecting gastrointestinal absorption in humans and rats. Food Chem Toxicol, 39, 209–28
   PubMed Web of Science ®Google Scholar
• Ekstrom LG, Kuivinen J, Johansson G. (1983). Molecular weight distribution and hydrolysis behavior of carrageenans. Carbohyd Res, 116, 89–94
   Google Scholar
• Ekstrom LG. (1985). Molecular-weight-distribution and the behavior of kappa-carrageenan on hydrolysis. Part II. Carbohydrate Res, 135, 283–9
   Google Scholar
• Falkoski DL, Guimaraes VM, Callegari CM, et al. (2006). Processing of soybean products by semipurified plant and microbial α-galactosidases. J Agric Food Chem, 54, 10184–90
   PubMedGoogle Scholar
• Farrall AL, Riemer P, Leushacke M, et al. (2012). Wnt and BMP signals control intestinal adenoma cell fates. Int J Cancer [Epub ahead of print]. doi:10.1002/ijc.27500
   Google Scholar
• George N. (1971). Human small intestinal β-galactosidases: separation and characterization of three forms of an acid β-galactosidase. Biochem J, 121, 299–308
   PubMedGoogle Scholar
• Grant BD, Donaldson JG. (2009). Pathways and mechanisms of endocytic recycling. Nat Rev Mol Cell Biol, 10, 597–608
   PubMed Web of Science ®Google Scholar
• Gray GM, Santiago NA. (1969). Intestinal β-galactosidases I. Separation and characterization of three enzymes in normal human intestine. J Clin Invest, 48, 716–28
   PubMed Web of Science ®Google Scholar
• Gregorieff A, Clevers H. (2005). Wnt signaling in the intestinal epithelium: from endoderm to cancer. Genes Dev, 19, 877–90
   PubMed Web of Science ®Google Scholar
• Gregorieff A, Pinto D, Begthel H, et al. (2012). Expression pattern of Wnt-signaling components in the adult intestine. Gastroenterology, 129, 626–38
   Google Scholar
• Gudjonsson T, Adriance, MC, Sternlicht MD, et al. (2005). Myoepithelial cells: their origin and function in breast morphogenesis and neoplasia. J Mammary Gland Biol Neoplasia, 10, 262–72
   Google Scholar
• Hanson SR, Best MD, Wong CH. (2004). Sulfatases: structure, mechanism, biological activity, inhibition, and synthetic utility. Angew Chem, Int Ed Engl, 43, 5736–63
   PubMed Web of Science ®Google Scholar
• Harmuth-Hoene AE, Schwerdtfeger E. (1979). Effect of indigestible polysaccharides on protein digestibility and nitrogen retention in growing rats. Nutr Metab, 23, 399–407
   PubMedGoogle Scholar
• Hsiao CC, Kao YH, Huang SC, Chuang JH. (2013). Toll-like receptor 4 agonist inhibits motility and invasion of hepatoblastoma HepG2 cells in vitro. Pediatr Blood Cancer, 60, 248–53
   PubMedGoogle Scholar
• Hughson EJ, Hopkins CR. (1990). Endocytic pathways in polarized Caco-2 cells: identification of an endosomal compartment accessible from both apical and basolateral surfaces. J Cell Biol, 110, 337–48
   PubMed Web of Science ®Google Scholar
• Ikegami S, Tsuchihashi F, Harada H, et al. (1990). Effect of viscous indigestible polysaccharides on pancreatic-biliary secretion and digestive organs. J Nutr, 120, 353–60
   PubMed Web of Science ®Google Scholar
• Incell Corporation, LLC, Normal derived colon mucosa (NCM460), INCELL NCM460 Product Information v1.0, 2007
   Google Scholar
• International Agency for Research on Cancer (IARC) Monograph. (1983). Carrageenan, 31, 79–94
   Google Scholar
• International Programme on Chemical Safety (IPCS) in cooperation with the Joint FAO/WHO Expert Committee on Food Additives (JECFA). (1999). Safety evaluation of certain food additives, WHO Food Additives Series 42, World Health Organization, Geneva
   Google Scholar
• Ishihara S, Rumi MAK, Ortega-Cava CF, et al. (2006). Therapeutic targeting of toll-like receptors in gastrointestinal inflammation. Jpn Curr Pharm Des, 12, 4215–28
   PubMedGoogle Scholar
• Ishioka T, Kuwabara N, Fukuda Y. (1985). Induction of colorectal adenocarcinoma in rats by amylopectin sulfate. Cancer Lett, 26, 277–82
   PubMedGoogle Scholar
• Ishioka T, Kuwabara N, Oohashi Y, Wakabayashi K. (1987). Induction of colorectal tumors in rats by sulfated polysaccharides. Crit Rev Toxicol, 17, 215–44
   PubMedGoogle Scholar
• Iwami KI, Matsuguchi T, Masuda A, et al. (2000). Cutting edge: naturally occurring soluble form of mouse toll-like receptor 4 inhibits lipopolysaccharide signaling. J Immunol, 165, 6682–6
   PubMed Web of Science ®Google Scholar
• Jacobs LR. (1987). Effect of dietary fiber on colonic cell proliferation and its relationship to colon carcinogenesis. Prev Med, 16, 566–71
   PubMed Web of Science ®Google Scholar
• Jansson EA, Are A, Greicius G, et al. (2005). The Wnt/beta-catenin signaling pathway targets PPARgamma activity in colon cancer cells. Proc Natl Acad Sci USA, 102, 1460–5
   PubMed Web of Science ®Google Scholar
• JECFA: Joint FAO/WHO expert committee on food additives. (2008). Sixty-eighth meeting of the joint FAO/WHO expert committee on food additives: safety evaluation of certain food additives and contaminants, held on 19–28 June 2007 in Geneva, Switzerland, WHO food additives series: 59, p. 65–85
   Google Scholar
• Kararli TT. (1995). Comparison of the gastrointestinal anatomy, physiology, and biochemistry of humans and commonly used laboratory animals. Biopharm Drug Disp, 16, 351–80
   PubMed Web of Science ®Google Scholar
• Kim YB, Nikoulina SE, Ciaraldi TP, et al. (1999). Normal insulin-dependent activation of Akt/protein kinase B, with diminished activation of phosphoinositide 3-kinase, in muscle in type 2 diabetes. J Clin Inest, 104, 733–41
   PubMed Web of Science ®Google Scholar
• Kolligs FT, Bommer G, Goke B. (2002). Wnt/beta-catenin/Tcf signaling: a critical pathway in gastrointestinal tumorigenesis. Digestion, 66, 131–44
   PubMed Web of Science ®Google Scholar
• Kosinski C, Li VSW, Chan ASY, et al. (2007). Gene expression patterns of human colon tops and basal crypts and BMP antagonists as intestinal stem cell niche factors. Proc Natl Acad Sci, 104, 15418–23
   PubMedGoogle Scholar
• Laroui H, Ingersoli SA, Liu HC, et al. (2012). Dextran sodium sulfate (DSS) induces colitis in mice by forming nano-lipocomplexes with medium-chain-length fatty acids in the colon. PLoS One, 7, e32084 . doi: 10.1371/journal.pone.0032084
   PubMed Web of Science ®Google Scholar
• Law IK, Murphy JE, Bakirtzi K, et al. (2012). Neurotensin-induced proinflammatory signaling in human colonocytes is regulated by β-arrestins and endothelin-converting enzyme-1-dependent endocytosis and resensitization of neurotensin receptor 1. J Biol Chem, 287, 15066–75
   PubMedGoogle Scholar
• LeBouder E, Rey-Nores JE, Raby AC, et al. (2006). Modulation of neonatal microbial recognition: TLR-mediated innate immune responses are specifically and differentially modulated by human milk. J Immunol, 176, 3742–52
   PubMedGoogle Scholar
• LeBouder E, Rey-Nores JE, Rushmere NK, et al. (2003). Soluble forms of toll-like receptor (TLR2) capable of modulating TLR2 signaling are present in human plasma and breast milk. J Immunol, 171, 6680–9
   PubMed Web of Science ®Google Scholar
• Lee S, Jo M, Lee J, et al. (2007). Identification of novel universal housekeeping genes by statistical analysis of microarray data. J Biochem Mol Biol, 40, 226–31
   PubMedGoogle Scholar
• Lemoine M, Collen PN, Helbert W. (2009). Physical state of κ-carrageenan modulates the mode of action of κ-carrageenase from pseudoalteromonas carrageenovora. Biochem J, 419, 545–53
   PubMedGoogle Scholar
• Liang Z, Wu S, Li Y, et al. (2011). Activation of toll-like receptor 3 impairs the dengue virus serotype 2 replication through induction of IFN-β in cultured hepatoma cells. PLoS One, 6, e23346
   PubMedGoogle Scholar
• Liew FY, Xu D, Brint EK, et al. (2005). Negative regulation of toll-like receptor-mediated immune responses. Nat Rev Immunol, 5, 446–58
   PubMed Web of Science ®Google Scholar
• Liu M-L, Hong S-T. (2005). Early phase of amyloid β2-induced cytotoxicity in neuronal cells is associated with vacuole formation and enhancement of exocytosis. Exp Mol Med, 37, 559–66
   PubMedGoogle Scholar
• Mallett AK, Rowland IR, Bearne CA, Nicklin S. (1985). Influence of dietary carrageenans on microbial biotransformation activities in the cecum of rodents and on gastrointestinal immune status in the rat. Toxicol Appl Pharmacol, 78, 377–85
   PubMed Web of Science ®Google Scholar
• Marcus R, Watt J. (1980). Potential hazards of carrageenan. Lancet, 315, 602–3
   Google Scholar
• Marcus SN, Marcus AJ, Marcus R, et al. (1992). The pre-ulcerative phase of carrageenan-induced colonic ulceration in the guinea-pig. Int J Exp Pathol, 73, 515–26
   PubMedGoogle Scholar
• Marrero JA, Matkowskyj KA, Yung K, et al. (2000). Dextran sulfate sodium-induced murine colitis activates NF-kB and increases galanin-1 receptor expression. Am J Physiol Gastrointest Liver Physiol, 278, G797–804
   PubMedGoogle Scholar
• Marroquin LD, Hynes K, Dulems JA, et al. (2007). Circumventing the crabtree effect: replacing media glucose with galactose increases susceptibility of HepG2 cells to mitochondrial toxicants. Toxicol Sci, 97, 2, 539–47
   Google Scholar
• McKim JM Jr. (2010). Building a tiered approach to in vitro predictive toxicity screening a focus on assays with in vivo relevance. Comb Chem HTS, 13, 188–206
   Google Scholar
• Miller YI, Choi S, Wiesner P, et al. (2011). Oxidation-specific epitopes are danger-associated molecular patterns recognized by pattern recognition receptors of innate immunity. Circ Res, 108, 235–48
   PubMed Web of Science ®Google Scholar
• Mohammad MK, Morran M, Slotterbeck B, et al. (2006). Dysregulated toll-like receptor expression and signaling in bone marrow-derived macrophages at the onset of diabetes in the non-obese diabetic mouse. Intern Immunol, 18, 1101–3
   PubMed Web of Science ®Google Scholar
• Mori H, Ohbayashi F, Hirono I, et al. (1984). Absence of genotoxicity of the carcinogenic sulfated polysaccharides carrageenan and dextran sulfate in mammalian DNA repair and bacterial mutagenicity assays. Nutr Cancer, 6, 92–7
   PubMedGoogle Scholar
• Morrin PJ, Sparks AB, Korinek V, et al. (1997). Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science, 275, 1787–90
   PubMedGoogle Scholar
• Moyana TN, Lalonde JM. (1990). Carrageenan-induced intestinal injury in the rat – a model for inflammatory bowel disease. Ann Clin Lab Sci, 6, 420–6
   Google Scholar
• Moyer MP, Manzano LA, Merriman RL, et al. (1996). NCM460, a normal human colon mucosal epithelial cell line. In Vitro Cell Dev Biol Anim, 32, 315--17
   PubMed Web of Science ®Google Scholar
• Nagler-Anderson C. (2001). Man the barrier! Strategic defences in the intestinal mucosa. Nat Rev Immunol, 1, 59–67
   PubMed Web of Science ®Google Scholar
• Naik S, Kelly EJ, Meijer L, et al. (2001). Absence of toll-like receptor 4 explains endotoxin hyporesponsiveness in human intestinal epithelium. J Pediatr Gastroenterol Nutr, 32, 449–53
   PubMedGoogle Scholar
• Nicklin S Miller K. (1983). Local and systemic immune responses to intestinally presented antigen. Int Arch Allergy Appl Immunol, 72, 87–90
   PubMedGoogle Scholar
• Nicklin S, Miller K. (1984). Effect of orally administered food-grade carrageenans on antibody-mediated and cell-mediated immunity in the inbred rat. Food Chem Toxicol, 22, 615–21
   PubMedGoogle Scholar
• Nishimura M, Naito S. (2005). Tissue-specific mRNA expression profiles of human toll-like receptors and related genes. Biol Pharm Bull, 28, 886–92
   PubMed Web of Science ®Google Scholar
• Nussbaumer P, Billich A. (2005). Steroid sulfatase inhibitors: their potential in the therapy of breast cancer. Curr Med Chem Anticancer Agents, 5, 507–28
   PubMedGoogle Scholar
• Olson NE. (2006). The microarray data analysis process: from raw data to biological significance. J Am Soc Exp Neuro Therap, 3, 373–83
   Google Scholar
• Onderdonk AB. (1985). Experimental models for ulcerative colitis. Dig Dis Sci, 30(12 Suppl), 40S–44S
   PubMedGoogle Scholar
• Oohashi Y, Ishioka T, Wakabayashi K, Kuwabara N. (1981). A study on carcinogenesis, induced by degraded carrageenan arising from squamous metaplasia of the rat colorectum. Cancer Lett, 14, 3, 267–72
   Google Scholar
• Osawa Y, Seki E, Kodama Y, et al. (2011). Acid sphingomyelinase regulates glucose and lipid metabolism in hepatocytes through AKT activation and AMP-activated protein kinase suppression. FASEB J, 25, 1133–44
   PubMed Web of Science ®Google Scholar
• Panaras DL, Martin GB. (1985). Molecular weight distribution of carrageenans by size exclusion chromatography and low angle laser light scattering. Carbohydr Polym, 5, 423–40
   Google Scholar
• Pandey PR, Saidou J, Watabe K. (2010). Role of myoepithelial cells in breast tumor progression. Front Biosci, 15, 226–36
   Google Scholar
• Paul DS, Harmon AW, Devesa V, et al. (2007). Molecular mechanisms of the diabetogenic effects of arsenic: inhibition of insulin signaling by arsenite and methylarsonous acid. Environ Health Perspect, 115, 734–42
   PubMed Web of Science ®Google Scholar
• Podolsky DK. (2000). Pride and prejudice: inflammatory bowel disease models and drug development. Curr Opin Gastroentero, 4, 295–6
   Google Scholar
• Poksay KS, Schneeman BO. (1983). Pancreatic and intestinal response to dietary guar gum in rats. J Nutr, 113, 1544–9
   PubMed Web of Science ®Google Scholar
• Prabhu SV, Bhattacharyya S, Guzman-Hartman G, et al. (2011). Extra-lysosomal localization of arylsulfatase B in human colonic epithelium. J Histochem Cytochem, 59, 328–35
   PubMedGoogle Scholar
• Ramsay AG, Scott KP, Martin JC. (2006). Cell-associated α-amylases of butyrate-producing firmicute bacteria from the human colon. Microbiology, 152, 3281–90
   PubMed Web of Science ®Google Scholar
• Ribon AOB, Queiroz MV, de Araujo EF. (2002). Structural organization of polygalacturonidase-encoding genes from Penicillium griseoroseum. Gen Mol Biol, 25, 489–93
   Google Scholar
• Rochas C, Heyraud A. (1981). Acid and enzymic hydrolysis of kappa carrageenan. Polym Bull, 5, 81–6
   Google Scholar
• Rustia M, Shubik P, Patil K. (1980). Lifespan carcinogenicity tests with native carrageenan in rats and hamsters. Cancer Lett, 11, 1–10
   PubMed Web of Science ®Google Scholar
• Rutenburg AM, Seligman AM. (1956). Colorimetric estimation of arylsulfatase: enzyme kinetics and distribution of the enzyme in seven mammals and in tumors. Arch Biochem Biophys, 60, 198–214
   PubMedGoogle Scholar
• Sagaert X, Van Cutsem E, De Hertogh G, et al. (2010). Gastric MALT lymphoma: a model of chronic inflammation-induced tumor development. Nat Rev Gastroenterol Hepatol, 7, 336–46
   PubMed Web of Science ®Google Scholar
• Sakanaka C, Sun TQ, Williams LT. (2000). New steps in the Wnt/beta-catenin signal transduction pathway. Recent Prog Horm Res, 55, 225–36
   PubMedGoogle Scholar
• SCF Scientific Committee on Food, European Commission Health & Consumer Protection Directorate General. (2003). Opinion of the scientific communities on food on carrageenan, 5 March 2003
   Google Scholar
• Schulz M, Schmoldt A. (2003). Therapeutic and toxic blood concentrations of more than 800 drugs and other xenobiotics. Pharmazie, 58, 447–74
   PubMed Web of Science ®Google Scholar
• Schoonen WG, Stevenson JC, Westerink WM, Horbach GJ. (2012). Cytotoxic effects of 109 reference compounds on rat H4IIE and human HepG2 hepatocytes. III: mechanistic assays on oxygen consumption with MitoXpress and NAD(P)H production with Alamar Blue™. Toxicol In Vitro, 3, 511–25
   Google Scholar
• Shi H, Kokoeva MV, Inouye K, et al. (2006). TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest, 116, 3015–25
   PubMed Web of Science ®Google Scholar
• Shroyer NF, Wong MH. (2007). BMP signaling in the intestine: cross-talk is key. Gastroenterology, 133, 1035–8
   PubMedGoogle Scholar
• Song MJ, Kim KH, Yoon JM, Kim JB. (2006). Activation of toll-like receptor 4 associated with insulin resistance in adipocytes. Biochem Biophys Res Commun, 346, 739–45
   PubMed Web of Science ®Google Scholar
• Sopel M. (2010). The myoepithelial cell: its role in normal mammary glands and breast cancer. Folia Morphol (Warsz), 69, 1–14
   PubMed Web of Science ®Google Scholar
• Stiles J, Guptill-Yoran L, Moore GE, Pogranichniy RM. (2008). Effects of lambda-carrageenan on in vitro replication of feline herpesvirus and on experimentally induced herpetic conjunctivitis in cats. Invest Ophthalmol Vis Sci, 49, 1496–501
   PubMed Web of Science ®Google Scholar
• Sun J, Zhuang FF, Mullersman JE, et al. (2006). BMP4 activation and secretion are negatively regulated by an intracellular gremlin-BMP4 interaction. J Biol Chem, 281, 29349–56
   PubMed Web of Science ®Google Scholar
• Takeuchi O, Akira S. (2001). Toll-like receptors; their physiological role and signal transduction system. Int Immunopharmacol, 4, 625–35
   Google Scholar
• Tobacman JK. (1997). Filament disassembly and loss of mammary myoepithelial cells after exposure to lambda-carrageenan. Cancer Res, 57, 2823–6
   PubMedGoogle Scholar
• Tobacman JK. (2001). Review of harmful gastrointestinal effects of carrageenan in animal experiments. Environ Health Perspect, 109, 983–94
   PubMed Web of Science ®Google Scholar
• Tobacman JK, Wallace RB, Zimmerman MB. (2001). Consumption of carrageenan and other water-soluble polymers used as food additives and incidence of mammary carcinoma. Med Hypotheses, 56, 589–98
   PubMed Web of Science ®Google Scholar
• Tobacman JK, Walters KS. (2001). Carrageenan-induced inclusions in mammary myoepithelial cells. Cancer Detect Prev, 25, 520–6
   PubMedGoogle Scholar
• Tusher VG, Tibshirani R, Chu G. (2001). Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci, 98, 5116–21
   PubMed Web of Science ®Google Scholar
• United Stated Adopted Names Council (USAN). (1988). List no. 297 new names, poligeenan. Clin Pharmacol Ther, 44, 246–8
   Google Scholar
• Uno Y, Omoto T, Goto Y, et al. (2001). Molecular weight and fecal excreted quantity of carrageenan administered to rats in blended feed. Jpn J Food Chem, 45, 98–106
   Google Scholar
• Van Eldere JR, Pauw GD, Eyssen HJ. (1987). Steroid sulfatase activity in a Peptococcus niger strain from the human intestinal microflora. Appl Environ Microbiol, 53, 1655–60
   PubMedGoogle Scholar
• Veber DF, Johnson SR, Cheng CY, et al. (2002). Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem, 45, 2615–23
   PubMed Web of Science ®Google Scholar
• Volpi N. (2002). Oral bioavailability of chondroitin sulfate (Condrosulf) and its constituents in healthy male volunteers. Osteoarthr Cartil, 10, 768–77
   PubMed Web of Science ®Google Scholar
• Wei XQ, Guo YW, Liu JJ, et al. (2008). The significance of toll-like receptor 4 (TLR4) expression in patients with chronic hepatitis B. Clin Invest Med, 31, E123–30
   PubMedGoogle Scholar
• Weiner ML. (1988). Intestinal transport of some macromolecules in food. Food Chem Toxicol, 26, 867–80
   PubMed Web of Science ®Google Scholar
• Weiner ML, Nuber D, Blakemore WR, et al. (2007). A 90-day dietary study on kappa carrageenan with emphasis on the gastrointestinal tract. Food Chem Toxicol, 45, 98–106
   PubMedGoogle Scholar
• Wilcox DK, Higgins J, Bertram TA. (1992). Colonic epithelial cell proliferation in a rat model of nongenotoxin-induced colonic neoplasia. Lab Invest, 67, 405–11
   PubMed Web of Science ®Google Scholar
• Xia C, Lu M, Zhang Z, et al. (2008). TLRs antiviral effect on hepatitis B virus in HepG2 cells. J Appl Microbiol, 105, 1720–7
   PubMed Web of Science ®Google Scholar
• Yang B, Bhattacharyya S, Linhardt R, Tobacman J. (2012). Exposure to common food additive carrageenan leads to reduced sulfatase activity and increase in sulfated glycosaminoglycans in human epithelial cells. Biochimie, 94, 1309–16
   PubMed Web of Science ®Google Scholar
• Zoran DL, Turner ND, Taddeo SS, et al. (1997). Wheat bran diet reduces tumor incidence in a rat model of colon cancer independent of effects on distal luminal butyrate concentrations. J Nutr, 127, 2217–25
   PubMed Web of Science ®Google Scholar