Aim To assess the impact of semi-refined carrageenan (E407a) on hydrophobic regions of phosphololipid bilayer in cell membranes of leukocytes collected from rats orally administered this food additive and white blood cells incubated with E407a. Methods Fluorescent probes (ortho-hydroxy derivatives of 2,5-diaryl-1,3-oxazole) were used to estimate the state of lipid bilayer in leukocytes obtained from rats orally exposed to the food additive E407a and in white blood cells incubated with E407a. Results No noticeable changes in the physico-chemical properties were observed in the lipid membranes of leukocytes in the region where the probes locate in response to oral intake of semi-refined carrageenan. Incubation of leukocytes with E407a solutions resulted in a decrease in polarity and proton-donor ability of leukocytes in the area of carbonyl groups of phospholipids and in the area of hydrocarbon chains of phospholipids near the polar region of the bilayer. Conclusion Membrane fluidity abnormalities found in cells exposed to E407a are similar to those observed in patients with IBD suggesting that contribution of carrageenan to IBD development may be partially explained by leukocyte membrane modifications.
Kurad D, Jeschke G, Marsh D. Lipid membrane polarity profiles by high-field EPR. Biophys J. 2003;1025–33.
2.
Martino J, Van Limbergen J, Cahill L. The role of carrageenan and carboxymethylcellulose in the development of intestinal inflammation. Front Pediatr. 2017;96.
3.
Bhattacharyya S, Shumard T, Xie H, Dodda A, Varady K, Feferman L, et al. A randomized trial of the effects of the no-carrageenan diet on ulcerative colitis disease activity. Nutr Healthy Aging. 2017;181–92.
4.
Pravda J. Crohn’s disease: evidence for involvement of unregulated transcytosis in disease etio-pathogenesis. World J Gastroenterol. 2011;1416–26.
5.
Bühner S, Nagel E, Körber J, Vogelsang H, Linn T, Pichlmayr R. Ileal and colonic fatty acid profiles in patients with active Crohn’s disease. Gut. 1994;1424–8.
6.
Aozaki S. Decreased membrane fluidity in erythrocytes from patients with Crohn’s disease. Gastroenterol Jpn. 1989;246–54.
7.
Tkachenko A, Marakushyn D, Kalashnyk I, Korniyenko Y, Onishchenko A, Gorbach T, et al. A study of enterocyte membranes during activation of apoptotic processes in chronic carrageenan-induced gastroenterocolitis. Med Glas (Zenica). 2018;87–92.
8.
Tkachenko A, Marakushyn D, Rezunenko Y, Onishchenko A, Nakonechna O, Posokhov Y. A study of erythrocyte membranes in carrageenaninduced gastroenterocolitis by method of fluorescent probes. HVM Bioflux. 2018;37–41.
9.
Posokhov Y, Kyrychenko A, Korniyenko Y, De. 4-oxadiazole as environment-sensitive fluorescent probes for studies of biological membranes. Geddes C Reviews in Fluorescence.
10.
Cham S. Springer Nature Switzerland AG. 2018;199–230.
11.
Doroshenko A, Posokhov E, Verezubova A, Ptyagina L, Skripkina V, Shershukov V. Radiationless deactivation of excited phototautomer form and molecular structure of ESIPT-compounds. Photochem Photobiol Sci. 2002;92–9.
12.
Doroshenko A, Posokhov E, Shershukov V, Mitina V, Ponomarev O. Intramolecular protontransfer reaction in an excited state in a series of ortho-hydroxy derivatives of 2,5-diaryloxazole. High Energy Chemistry. 1997;388–94.
13.
Posokhov Y, Kyrychenko A. Location of fluorescent probes (2-hydroxy derivatives of 2,5-diaryl-1,3oxazole) in lipid membrane studied by fluorescence spectroscopy and molecular dynamics simulation. Biophys Chem. 2018;9–18.
14.
Borthakur A, Bhattacharyya S, Dudeja P. Tobacman JK. Carrageenan induces interleukin-8 production through distinct Bcl10 pathway in normal human colonic epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2007;829–38.
15.
Bartucci R, Guzzi R, Marsh D, Sportelli L. Intramembrane polarity by electron spin echo spectroscopy of labeled lipids. Biophys J. 2003;(2):1025–30.
16.
Ho C, Slater S, Stubbs C. Hydration and order in lipid bilayers. Biochemistry. 1995;6188–95.
17.
Binder H, Gawrisch K. Effect of unsaturated lipid chains on dimensions, molecular order and hydration of membranes. J Phys Chem B. 2001;12378–90.
18.
Noethig-Laslo V, Šentjurc M. Advances in Planar Lipid Bilayers and Liposomes. 2006;365–415.
19.
Levental K, Malmberg E, Symons J, Fan Y, Chapkin R, Ernst R, et al. Lipidomic and biophysical homeostasis of mammalian membranes counteracts dietary lipid perturbations to maintain cellular fitness. Nat Commun. 2020;1339.
20.
Desai A, Miller L. Changes in the plasma membrane in metabolic disease: impact of the membrane environment on G protein-coupled receptor structure and function. Br J Pharmacol. 2018;4009–25.
21.
Seely A, Pascual J, Christou N. Science review: Cell membrane expression (connectivity) regulates neutrophil delivery, function and clearance. Crit Care. 2003;291–307.
22.
Kantar A, Oggiano N, Giorgi P, Fiorini R. Membrane fluidity of polymorphonuclear leukocytes from children with primary ciliary dyskinesia. Pediatr Res. 1993;725–8.
23.
Gaschler M, Stockwell B. Lipid peroxidation in cell death. Biochem Biophys Res Commun. 2017;419–25.
24.
Chen J, Yu B. Alterations in mitochondrial membrane fluidity by lipid peroxidation products. Free Radic Biol Med. 1994;411–8.
25.
Sokolova E, Karetin Y, Davydova V, Byankina A, Kalitnik A, Bogdanovich L, et al. Carrageenans effect on neutrophils alone and in combination with LPS in vitro. J Biomed Mater Res A. 2016;1603–9.
26.
Boyle J, Parkhouse R, Monie T. Insights into the molecular basis of the NOD2 signalling pathway. Open Biol. 2014;140178.
27.
Knight-Sepulveda K, Kais S, Santaolalla R, Abreu M. Diet and inflammatory bowel disease. Gastroenterol Hepatol (N Y). 2015;511–20.
28.
Seyedian S, Nokhostin F, Malamir M. A review of the diagnosis, prevention, and treatment methods of inflammatory bowel disease. J Med Life. 2019;113–22.
29.
Perler B, Ungaro R, Baird G, Mallette M, Bright R, Shah S, et al. Presenting symptoms in inflammatory bowel disease: descriptive analysis of a community-based inception cohort. BMC Gastroenterol. 2019;47.
30.
Qin X. Why is damage limited to the mucosa in ulcerative colitis but transmural in Crohn’s disease? World J Gastrointest Pathophysiol. 2013;63–4.
31.
Gbd. Inflammatory Bowel Disease Collaborators. The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study. Lancet Gastroenterol Hepatol. 2017;17–30.
32.
Hadi A, L, Vito D, Riboni C, L. Fostering inflammatory bowel disease: sphingolipid strategies to join forces. Mediators Inflamm. 2016;3827684.
33.
Verstockt B, Smith K, Lee J. Genome-wide association studies in Crohn’s disease: past, present and future. Clin Transl Immunology. 2018;1001.
34.
Yamamoto S, Ma X. Role of NOD 2 in the development of Crohn’s disease. Microbes Infect. 2009;912–8.
35.
Hugot J. CARD15/NOD2 mutations in Crohn’s disease. Ann N Y Acad Sci. 2006;9–18.
36.
Ogura Y, Bonen D, Inohara N, Nicolae D, Chen F, Ramos R, et al. A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease. Nature. 2001;603–6.
37.
Negroni A, Pierdomenico M, Cucchiara S, Stronati L. NOD2 and inflammation: current insights. J Inflamm Res. 2018;49–60.
38.
Lewis J, Abreu M. Diet as a trigger or therapy for inflammatory bowel diseases. Gastroenterology. 2017;398–414.
39.
Ferrand A, Nabhani A, Tapias Z, Mas N, Hugot E, Barreau J, et al. NOD2 expression in intestinal epithelial cells protects toward the development of inflammation and associated carcinogenesis. Cell Mol Gastroenterol Hepatol. 2019;357–69.
40.
Sidiq T, Yoshihama S, Downs I, Kobayashi K. Nod2: A critical regulator of ileal microbiota and Crohn’s disease. Front Immunol. 2016;367.
41.
Vedamurthy A, Ananthakrishnan A. Influence of environmental factors in the development and outcomes of inflammatory bowel disease. Gastroenterol Hepatol (N Y). 2019;72–82.
42.
Rizzello F, Spisni E, Giovanardi E, Imbesi V, Salice M, Alvisi P, et al. Implications of the westernized diet in the onset and progression of IBD. Nutrients. 2019;1033.
43.
Bui T. Structure, rheological properties and connectivity of gels formed by carrageenan extracted from different red algae species. Organic Chemistry. 2019;
44.
Necas J, Bartosikova L. Carrageenan: a review. Veterinarni Medicina. 2013;187–205.
45.
Heikenwälder H, Heikenwälder M. Krebs -Lifestyle und Umweltfaktoren als Risiko. 2019;
46.
Younes M, Aggett P, Aguilar F, Crebelli R, Filipič M, Frutos M, et al. Re-evaluation of carrageenan (E407) and processed Eucheuma seaweed (E407a) as food additives. EFSA J. 2018;5238.
47.
Feferman L, Bhattacharyya S, Oates E, Haggerty N, Wang T, Varady K, et al. Carrageenan-free diet shows improved glucose tolerance and insulin signaling in prediabetes: a randomized, pilot clinical trial. J Diabetes Res. 2020;8267980.
48.
Tobacman J. Review of harmful gastrointestinal effects of carrageenan in animal experiments. Environ Health Perspect. 2001;983–94.
49.
Bhattacharyya S, Gill R, Chen M, Zhang F, Linhardt R, Dudeja P, et al. Toll-like receptor 4 mediates induction of the Bcl10-NFkappaB-interleukin-8 inflammatory pathway by carrageenan in human intestinal epithelial cells. J Biol Chem. 2008;10550–8.
The statements, opinions and data contained in the journal are solely those of the individual authors and contributors and not of the publisher and the editor(s). We stay neutral with regard to jurisdictional claims in published maps and institutional affiliations.