DOI: https://doi.org/10.22263/2312-4156.2018.1.7
Tkachenko A.S.1, Nakonechna O.A.1, Gorbach Т.V.1, Tkachenko M.A.2
Carrageenans: are they useful or detrimental?
1Kharkov National Medical University, Kharkov, Ukraine
2Kharkov Municipal Clinical Hospital No.27, Kharkov, Ukraine
Vestnik VGMU. 2018;17(1):7-13.
Abstract.
Carrageenans are sulfated heteropolysaccharides of red algae, that are used in the food industry as thickeners and emulsifiers (E407). Both positive and negative effects of carrageenans on the body have been reported. This review deals with information about the experiments in which the ability of carrageenans to act as inducers of inflammation and carcinogenesis is demonstrated, antioxidant, antiviral and antitumor effects of carrageenans are also described. After analyzing the sources, we have concluded that the properties of carrageenans depend primarily on the type and molecular weight of macromolecules. Controversial data on the toxic effects of carrageenans from in vivo and in vitro investigations indicate the need for careful interpretation of the results of experiments, that demonstrate the safety of the E407 food additive, and prevent from blindly transferring the results of in vitro studies of the biosafety of carrageenans to humans.
Key words: food additives, carrageenan, carrageenan-induced inflammation, antioxidants, antitumor effect.
References
1. Manuhara GJ, Praseptiangga D, Riyanto RA. Extraction and characterization of refined k-carrageenan of red algae [Kappaphycus Alvarezii (Doty ex p.c. Silva, 1996)] originated from karimun jawa islands. Aquatic Procedia. 2016 Aug;7:106-11. doi: http://dx.doi.org/10.1016/j.aqpro.2016.07.014
2. Necas J, Bartosikova L. Carrageenan: a review. Veterinarni Medicina. 2013;58(4):187-205.
3. Azevedo G, Hilliou L, Ronald GB, Villanueva D, William R, Nilsson AM, et al. Tailoring kappa/iota-hybrid carrageenan from Mastocarpus stellatus with desired gel quality through pre-extraction alkali treatment. Food Hydrocoll. 2013 May;31(1):94-102. doi: http://dx.doi.org/10.1016/j.foodhyd.2012.10.010
4. Safety evaluation of certain food additives [Electronic resource]: WHO Food Additives Series: 70: Prepared by the Seventy-ninth meeting of the Joint FAO/WHO Expert Committee on Food Additives (JECFA). Geneva: World Health Organization$ 2015. Mode of access: http://apps.who.int/iris/bitstream/10665/171781/3/9789240693982_eng.pdf. Date of access: 11.11.2017.
5. Tobacman JK. Review of harmful gastrointestinal effects of carrageenan in animal experiments. Environ Health Perspect. 2001 Oct;109(10):983-94.
6. Іvanenko TO, Korobchans'kiy VO, Gubіna-Vakulik GІ, Gorbach TV, Kolousova NG; zaiavnik і vlasnik patentu Kharkіv Nats Med Un-t. Way of modeling of a chronic gastroenterocolitis: pat 97322 Ukraїna, MPK G 09 B 23/28. № a201014510; zaiavl 06.12.10; opubl 25.01.12, Biul № 2. (In Ukr.)
7. Gubina-Vakulik GA, Tkachenko AS, Orlova MA. Morphological condition of the small intestine with prolonged use of the food additive carrageenan. Vіsn Problem Bіologії Meditsini. 2014;3(vip 2):252-7. (In Russ.)
8. Pricolo VE, Madhere SM, Finkelstein SD, Reichner JS. Effects of lambda-carrageenan induced experimental enterocolitis on splenocyte function and nitric oxide production. J Surg Res. 1996 Nov;66(1):6-11.
9. Gubina-Vakyulyk GI, Gorbach TV, Tkachenko AS, Tkachenko MO. Damage and regeneration of small intestinal enterocytes under the influence of carrageenan induces chronic enteritis. Comp Clin Path. 2015 Nov;24(6):1473-7. doi: http://dx.doi.org/10.1007/s00580-015-2102-3
10. Watt J, Marcus R. Experimental ulcerative disease of the colon in animals. Gut. 1973 Jun;14(6):506-10.
11. Tkachenko AS. The level of VEGF and TNF-α in chronic carrageenan-induced gastroenterocolitis. Vіsn Problem Bіologії Meditsini. 2013;2(vip 3):231-4. (In Russ.)
12. Tkachenko AS, Gopkalov VG. The state of prooxidant-antioxidant system in chronic experimental gastroenterocolitis. Vіsn Problem Bіologії Meditsini. 2014;1(vip 1):194-9. (In Ukr.)
13. Tkachenko AS, Kornienko EM, Posokhov EA. Apoptosis of enterocytes during chronic carrageenan-induced gastroenterocolitis: study by fluorescent probes. Vіsn Kharkіv Nats Un-tu іm VN Karazіna Ser Bіologіia. 2016;(vip 26);179-86. (In Russ.)
14. Zhukov VI, Tkachenko AS. The level of tumor necrosis factor alpha and activity of matrix metalloproteinase-2 in chronic carrageenan-induced gastroenterocolitis. Nauch Ved BelGU Ser Meditsina Farmatsiia. 2014;(18 vyp 27):150-3. (In Russ.)
15. Zhukov VI, Tkachenko AS. The system of lipid peroxidation and activity of apoptosis in experimental chronic gastroenterocolitis. Nauch Ved BelGU Ser Meditsina Farmatsiia. 2013;(18 vyp 23):138-41. (In Russ.)
16. Martino JV, Van Limbergen J, Cahill LE. The role of carrageenan and carboxymethylcellulose in the development of intestinal inflammation. Front Pediatr. 2017 May;5:96. doi: http://dx.doi.org/10.3389/fped.2017.00096
17. Chan CC, Boyce S, Brideau C, Ford-Hutchinson AW, Gordon R, Guay D, et al. Pharmacology of a selective cyclooxygenase-2 inhibitor, L-745,337: a novel nonsteroidal anti-inflammatory agent with an ulcerogenic sparing effect in rat and nonhuman primate stomach. J Pharmacol Exp Ther. 1995 Sep;274(3):1531-7.
18. Hassimotto NM, Moreira V, do Nascimento NG, Souto PC, Teixeira C, Lajolo FM. Inhibition of carrageenan-induced acute inflammation in mice by oral administration of anthocyanin mixture from wild mulberry and cyanidin-3-glucoside. Biomed Res Int. 2013;2013:146716. doi: http://dx.doi.org/10.1155/2013/146716
19. Barth CR, Funchal GA, Luft C, de Oliveira JR, Porto BN, Donadio MV, et al. Carrageenan-induced inflammation promotes ROS generation and neutrophil extracellular trap formation in a mouse model of peritonitis. Eur J Immunol. 2016 Apr;46(4):964-70. doi: http://dx.doi.org/10.1002/eji.201545520
20. Hansra P, Moran EL, Fornasier VL, Bogoch ER. Carrageenan-induced arthritis in the rat. Inflammation. 2000 Apr;24(2):141-55.
21. Chamberland DL, Wang X, Roessler BJ. Photoacoustic tomography of carrageenan-induced arthritis in a rat model. J Biomed Opt. 2008 Jan-Feb;13(1):011005. doi: http://dx.doi.org/10.1117/1.2841028
22. Zeng F, Chen H, Yang J, Wang L, Cui Y, Guan X1, et al. Development and validation of an animal model of prostate inflammation-induced chronic pelvic pain: evaluating from inflammation of the prostate to pain behavioral modifications. PLoS One. 2014 May;9(5):e96824. doi: http://dx.doi.org/10.1371/journal.pone.0096824
23. Wang GQ, Xu T, Bu XM, Liu BY. Anti-inflammation effects of corn silk in a rat model of carrageenin-induced pleurisy. Inflammation. 2012 Jun;35(3):822-7. doi: http://dx.doi.org/10.1007/s10753-011-9382-9
24. Gamache DA, Povlishock JT, Ellis EF. Carrageenan-induced brain inflammation. Characterization of the model. J Neurosurg. 1986 Nov;65(5):679-85.
25. Yuan H, Song J, Zhang W, Li X, Li N, Gao X. Antioxidant activity and cytoprotective effect of kappa-carrageenan oligosaccharides and their different derivatives. Bioorg Med Chem Lett. 2006 Mar;16(5):1329-34. doi: http://dx.doi.org/10.1016/j.bmcl.2005.11.057
26. Sun Y, Yang B, Wu Y, Liu Y, Gu X, Zhang H, et al. Structural characterization and antioxidant activities of κ-carrageenan oligosaccharides degraded by different methods. Food Chem. 2015 Jul;178:311-8. doi: http://dx.doi.org/10.1016/j.foodchem.2015.01.105
27. Abad LV, Relleve LS, Racadio CD, Aranilla CT, De la Rosa AM. Antioxidant activity potential of gamma irradiated carrageenan. Appl Radiat Isot. 2013 Sep;79:73-9. doi: http://dx.doi.org/10.1016/j.apradiso.2013.04.035
28. Relleve L, Abad L. Characterization and antioxidant properties of alcoholic extracts from gamma irradiated κ-carrageenan. Radiat Phys Chem. 2015 Jul;112:40-8. doi: http://dx.doi.org/10.1016/j.radphyschem.2015.02.028
29. Weiner ML. Food additive carrageenan: Part II: a critical review of carrageenan in vivo safety studies. Crit Rev Toxicol. 2014 Mar;44(3):244-69. doi: http://dx.doi.org/10.3109/10408444.2013.861798
30. González ME, Alarcón B, Carrasco L. Polysaccharides as antiviral agents: antiviral activity of carrageenan. Antimicrob Agents Chemother. 1987 Sep;31(9):1388-93.
31. Chiu YH, Chan YL, Tsai LW, Li TL, Wu CJ. Prevention of human enterovirus 71 infection by kappa carrageenan. Antiviral Res. 2012 Aug;95(2):128-34. doi: http://dx.doi.org/10.1016/j.antiviral.2012.05.009
32. Leibbrandt A, Meier C, König-Schuster M, Weinmüllner R, Kalthoff D, Pflugfelder B, et al. Iota-carrageenan is a potent inhibitor of influenza A virus infection. PLoS One. 2010 Dec;5(12):e14320. doi: http://dx.doi.org/10.1371/journal.pone.0014320
33. Talarico LB, Noseda MD, Ducatti DR, Duarte ME, Damonte EB. Differential inhibition of dengue virus infection in mammalian and mosquito cells by iota-carrageenan. J Gen Virol. 2011 Jun;92(Pt 6):1332-42. doi: http://dx.doi.org/10.1099/vir.0.028522-0
34. Buck CB, Thompson CD, Roberts JN, Müller M, Lowy DR, Schiller JT. Carrageenan is a potent inhibitor of papillomavirus infection. PLoS Pathog. 2006 Jul;2(7):e69. doi: http://dx.doi.org/10.1371/journal.ppat.0020069
35. Ji J, Wang L-C, Wu H, Luan H-M. Bio-function summary of marine oligosaccharides. Int J Biol. 2011;3(1):74-86. doi: http://dx.doi.org/10.5539/ijb.v3n1p74
36. Grassauer A, Weinmuellner R, Meier C, Pretsch A, Prieschl-Grassauer E, Unger H. Iota-Carrageenan is a potent inhibitor of rhinovirus infection. Virol J. 2008;5:107. doi: http://dx.doi.org/10.1186/1743-422X-5-107
37. Mizokami SS, Hohmann MS, Staurengo-Ferrari L, Carvalho TT, Zarpelon AC, Possebon MI, et al. Pimaradienoic acid inhibits carrageenan-induced inflammatory leukocyte recruitment and edema in mice: inhibition of oxidative stress, nitric oxide and cytokine production. PLoS One. 2016 Feb;11(2):e0149656. doi: http://dx.doi.org/10.1371/journal.pone.0149656
38. Chan WI, Zhang G, Li X, Leung CH, Ma DL, Dong L, et al. Carrageenan activates monocytes via type-specific binding with interleukin-8: an implication for design of immuno-active biomaterials. Biomater Sci. 2017 Feb;5(3):403-407. doi: http://dx.doi.org/10.1039/c6bm00799f
39. Fedorov SN, Ermakova SP, Zvyagintseva TN, Stonik VA. Anticancer and cancer preventive properties of marine polysaccharides: some results and prospects. Mar Drugs. 2013 Dec;11(12):4876-901. doi: http://dx.doi.org/10.3390/md11124876
40. Hu X, Jiang X, Aubree E, Boulenguer P, Critchley AT. Preparation and in vivo antitumor activity of kappa-carrageenan oligosaccharides. Pharm Biol. 2006;44:646-50. doi: http://dx.doi.org/10.1080/13880200601006848
41. Prasedya ES, Miyake M, Kobayashi D, Hazama A. Carrageenan delays cell cycle progression in human cancer cells in vitro demonstrated by FUCCI imaging. BMC Complement Altern Med. 2016 Aug;16:270. doi: http://dx.doi.org/10.1186/s12906-016-1199-5
42. Luo M, Shao B, Nie W, Wei XW, Li YL, Wang BL, et al. Antitumor and adjuvant activity of λ-carrageenan by stimulating immune response in cancer immunotherapy. Sci Rep. 2015 Jun;5:11062. doi: http://dx.doi.org/10.1038/srep11062
43. Zhou G, Xin H, Sheng W, Sun Y, Li Z, Xu Z. In vivo growth-inhibition of S180 tumor by mixture of 5-Fu and low molecular lambda-carrageenan from Chondrus ocellatus. Pharmacol Res. 2005 Feb;51(2):153-7.
44. Yuan H, Song J, Li X, Li N, Dai J. Immunomodulation and antitumor activity of kappa-carrageenan oligosaccharides. Cancer Lett. 2006 Nov;243(2):228-34. doi: http://dx.doi.org/10.1016/j.canlet.2005.11.032
Information about authors:
Tkachenko A.S. – Candidate of Medical Sciences, lecturer of the Chair of Biochemistry, Kharkov National Medical University;
Nakonechna O.A. – Doctor of Medical Sciences, professor, head of the Chair of Biochemistry, Kharkov National Medical University;
Gorbach T.V. – Candidate of Biological Sciences, associate professor of the Chair of Biochemistry, Kharkov National Medical University;
Tkachenko M.A. – intern, Kharkov Municipal Clinical Hospital No.27.
Correspondence address: Ukraine, 61022, Kharkov, 4 Nauky ave., Kharkov National Medical University, Chair of Biochemistry. E-mail: Этот адрес электронной почты защищён от спам-ботов. У вас должен быть включен JavaScript для просмотра. – Anton S. Tkachenko.
