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12.08.2021 | original article

Food additive E407a stimulates eryptosis in a dose-dependent manner

verfasst von: Dr. Anton Tkachenko, MD, PhD, Dr. Yurii Kot, PhD, Dr. Volodymyr Prokopyuk, MD, PhD, Dr. Anatolii Onishchenko, MD, PhD, Dr. Alla Bondareva, PhD, Prof. Valeriy Kapustnik, MD, PhD, DSc, Prof. Tetyana Chumachenko, MD, PhD, DSc, Prof. Yevgen Perskiy, PhD, DSc, Prof. Dmytro Butov, MD, PhD, DSc, Prof. Oksana Nakonechna, MD, PhD, DSc

Erschienen in: Wiener Medizinische Wochenschrift | Ausgabe 5-6/2022

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Summary

Background

Concerns about the biosafety of the common food additive E407a have been raised. It has been demonstrated to induce intestinal inflammation, accompanied by activation of apoptosis, upon oral exposure. Thus, it is of interest to investigate how E407a affects eryptosis, a suicidal cell death mode of red blood cells.

Objective

To evaluate the effects of semi-refined carrageenan (E407a) on eryptosis.

Methods

Flow cytometry was employed to assess eryptosis in blood exposed to various concentrations of E407a (0 g/L, 1 g/L, 5 g/L, and 10 g/L) during incubation for 24 h by analyzing phosphatidylserine externalization in erythrocytes using annexin V staining and via evaluating reactive oxygen species (ROS) generation using 2′,7′-dichlorodihydrofluorescein diacetate (H₂DCFDA). In addition, the eryptosis indices mentioned above were determined in rats orally administered E407a at a dose of 140 mg/kg weight for 2 weeks. Confocal scanning laser microscopy was performed to visualize cell membrane scrambling.

Results

Oral intake of E407a for 2 weeks by rats was not associated with membrane scrambling in erythrocytes. However, ROS overproduction was observed. Meanwhile, incubation of blood with various concentrations of semi-refined carrageenan resulted in a dose-dependent promotion of eryptosis, evidenced by the enhanced percentage of annexin V-positive erythrocytes and higher mean fluorescence intensity (MFI) values of annexin V-FITC in all erythrocytes. The highest concentration of E407a promotes a statistically significant increase in ROS generation in erythrocytes, suggesting the role of ROS-mediated induction of eryptosis in this case.

Conclusion

Incubation of blood with the food additive E407a leads to the activation of eryptosis in a dose-dependent manner. ROS-mediated mechanisms are partially responsible for E407a-induced eryptosis.

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Besednova NN, Zvyagintseva TN, Kuznetsova TA, et al. Marine algae metabolites as promising therapeutics for the prevention and treatment of HIV/AIDS. Metabolites. 2019;9(5):87. https://doi.org/10.3390/metabo9050087.CrossRefPubMedCentral

Kim JH, Lee JE, Kim KH, et al. Beneficial effects of marine algae-derived carbohydrates for skin health. Mar Drugs. 2018;16(11):459. https://doi.org/10.3390/md16110459.CrossRefPubMedCentral

Kang HK, Seo CH, Park Y. The effects of marine carbohydrates and glycosylated compounds on human health. Int J Mol Sci. 2015;16(3):6018–56. https://doi.org/10.3390/ijms16036018.CrossRefPubMedPubMedCentral

Wang W, Wang SX, Guan HS. The antiviral activities and mechanisms of marine polysaccharides: an overview. Mar Drugs. 2012;10(12):2795–816. https://doi.org/10.3390/md10122795.CrossRefPubMedPubMedCentral

Weiner ML. Food additive carrageenan: part II: a critical review of carrageenan in vivo safety studies. Crit Rev Toxicol. 2014;44(3):244–69. https://doi.org/10.3109/10408444.2013.861798.CrossRefPubMed

Saha D, Bhattacharya S. Hydrocolloids as thickening and gelling agents in food: a critical review. J Food Sci Technol. 2010;47:587–97. https://doi.org/10.1007/s13197-010-0162-6.CrossRefPubMedPubMedCentral

David S, Shani Levi C, Fahoum L, et al. Revisiting the carrageenan controversy: Do we really understand the digestive fate and safety of carrageenan in our foods? Food Funct. 2018;9(3):1344–52. https://doi.org/10.1039/c7fo01721a.CrossRefPubMed

Younes M, Aggett P, Aguilar F, et al. Re-evaluation of carrageenan (E 407) and processed Eucheuma seaweed (E 407a) as food additives, European Food Safety Authority, FSA ANS panel (EFSA panel on food additives and nutrient sources added to food), 2018. EFSA J. 2018;16(4):5238. https://doi.org/10.2903/j.efsa.2018.5238.CrossRef

Tkachenko AS, Onishchenko AI, Gorbach TV, et al. O‑6-methylguanine-DNA methyltransferase (MGMT) overexpression in small intestinal mucosa in experimental carrageenan-induced enteritis. Malay J Biochem Mol Biol. 2018;21(3):77–80.

10.

Gubina-Vakyulyk GI, Gorbach TV, Tkachenko AS, et al. Damage and regeneration of small intestinal enterocytes under the influence of carrageenan induces chronic enteritis. Comp Clin Pathol. 2015;24(6):1473–7. https://doi.org/10.1007/s00580-015-2102-3.CrossRef

11.

Necas J, Bartosikova L. Carrageenan: a review. Vet Med (Praha). 2013;58:187–205.CrossRef

12.

Cohen SM, Ito N. A critical review of the toxicological effects of carrageenan and processed eucheuma seaweed on the gastrointestinal tract. Crit Rev Toxicol. 2002;32(5):413–44. https://doi.org/10.1080/20024091064282.CrossRefPubMed

13.

Tobacman JK. Review of harmful gastrointestinal effects of carrageenan in animal experiments. Environ Health Perspect. 2001;109(10):983–94. https://doi.org/10.1289/ehp.01109983.CrossRefPubMedPubMedCentral

14.

Tkachenko A, Marakushyn D, Kalashnyk I, et al. A study of enterocyte membranes during activation of apoptotic processes in chronic carrageenan-induced gastroenterocolitis. Med Glas (Zenica). 2018;15(2):87–92. https://doi.org/10.17392/946-18.CrossRef

15.

Lang F, Lang E, Föller M. Physiology and pathophysiology of eryptosis. Transfus Med Hemother. 2012;39(5):308–14. https://doi.org/10.1159/000342534.CrossRefPubMedPubMedCentral

16.

Boulet C, Doerig CD, Carvalho TG. Manipulating eryptosis of human red blood cells: a novel antimalarial strategy? Front Cell Infect Microbiol. 2018;8:419. https://doi.org/10.3389/fcimb.2018.00419. published correction appears in Front Cell Infect Microbiol. 2019 8:455.CrossRefPubMedPubMedCentral

17.

Repsold L, Joubert AM. Eryptosis: an erythrocyte’s suicidal type of cell death. Biomed Res Int. 2018;2018:9405617. https://doi.org/10.1155/2018/9405617.CrossRefPubMedPubMedCentral

18.

Egler J, Lang F. Triggering of eryptosis, the suicidal erythrocyte death, by perifosine. Cell Physiol Biochem. 2017;41(6):2534–44. https://doi.org/10.1159/000475977.CrossRefPubMed

19.

Lang E, Lang F. Triggers, inhibitors, mechanisms, and significance of eryptosis: the suicidal erythrocyte death. Biomed Res Int. 2015;2015:513518. https://doi.org/10.1155/2015/513518.CrossRefPubMedPubMedCentral

20.

Bozza MT, Jeney V. Pro-inflammatory actions of heme and other hemoglobin-derived DAMPs. Front Immunol. 2020;11:1323. https://doi.org/10.3389/fimmu.2020.01323.CrossRefPubMedPubMedCentral

21.

Hod EA. Consequences of hemolysis: pro-inflammatory cytokine response to erythrophagocytosis. Transfus Clin Biol. 2019;26(2):125–7. https://doi.org/10.1016/j.tracli.2019.02.005.CrossRefPubMed

22.

Wiewiora M, Piecuch J, Sedek L, et al. The effects of obesity on CD47 expression in erythrocytes. Cytometry B Clin Cytom. 2017;92(6):485–91. https://doi.org/10.1002/cyto.b.21232.CrossRefPubMed

23.

Ran Q, Xiang Y, Liu Y, et al. Eryptosis indices as a novel predictive parameter for biocompatibility of Fe₃O₄ magnetic nanoparticles on erythrocytes. Sci Rep. 2015;5:16209. https://doi.org/10.1038/srep16209.CrossRefPubMedPubMedCentral

24.

Tkachenko AS, Kot YG, Kapustnik VA, et al. Semi-refined carrageenan promotes reactive oxygen species (ROS) generation in leukocytes of rats upon oral exposure but not in vitro. Wien Med Wochenschr. 2020; https://doi.org/10.1007/s10354-020-00786-7.CrossRefPubMed

25.

Barth CR, Funchal GA, Luft C, et al. Carrageenan-induced inflammation promotes ROS generation and neutrophil extracellular trap formation in a mouse model of peritonitis. Eur J Immunol. 2016;46(4):964–70. https://doi.org/10.1002/eji.201545520.CrossRefPubMed

26.

Abe T, Kawamura H, Kawabe S, et al. Liver injury due to sequential activation of natural killer cells and natural killer T cells by carrageenan. J Hepatol. 2002;36(5):614–23.CrossRef

27.

McKim JM Jr, Baas H, Rice GP, et al. Effects of carrageenan on cell permeability, cytotoxicity, and cytokine gene expression in human intestinal and hepatic cell lines. Food Chem Toxicol. 2016;96:1–10. https://doi.org/10.1016/j.fct.2016.07.006.CrossRefPubMed

28.

McKim JM. Food additive carrageenan: part I: a critical review of carrageenan in vitro, studies, potential pitfalls, and implications for human health and safety. Crit Rev Toxicol. 2014;40:210–43.

29.

Tkachenko AS, Marakushyn DI, Rezunenko YK, et al. A study of erythrocyte membranes in carrageenan-induced gastroenterocolitis by method of fluorescent probes. HVM Bioflux. 2018;10(2):37–41.

30.

Amponin MO, Manabat CH, Quintos RT. The oxygen-binding capacity of human erythrocyte in iota-carrageenan solution and conventional plasma expanders. Clin Hemorheol Microcirc. 2003;29(3–4):263–70.PubMed

31.

Pretorius E, du Plooy JN, Bester J. A comprehensive review on eryptosis. Cell Physiol Biochem. 2016;39(5):1977–2000. https://doi.org/10.1159/000447895.CrossRefPubMed

32.

Malik A, Bissinger R, Liu G, et al. Enhanced eryptosis following gramicidin exposure. Toxins (Basel). 2015;7(5):1396–410. https://doi.org/10.3390/toxins7051396.CrossRef

33.

Lopes AH, Silva RL, Fonseca MD, et al. Molecular basis of carrageenan-induced cytokines production in macrophages. Cell Commun Signal. 2020;18(1):141. https://doi.org/10.1186/s12964-020-00621-x.CrossRefPubMedPubMedCentral

34.

Myers MJ, Deaver CM, Lewandowski AJ. Molecular mechanism of action responsible for carrageenan-induced inflammatory response. Mol Immunol. 2019;109:38–42. https://doi.org/10.1016/j.molimm.2019.02.020.CrossRefPubMed

35.

Sokolova EV, Karetin Y, Davydova VN, et al. Carrageenans effect on neutrophils alone and in combination with LPS in vitro. J Biomed Mater Res A. 2016;104(7):1603–9. https://doi.org/10.1002/jbm.a.35693.CrossRefPubMed

36.

Bhattacharyya S, Gill R, Chen ML, 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;283(16):10550–8. https://doi.org/10.1074/jbc.M708833200.CrossRefPubMedPubMedCentral

37.

Weiner ML, McKim JM. Comment on “Revisiting the carrageenan controversy: Do we really understand the digestive fate and safety of carrageenan in our foods?” by S. David, C. S. Levi, L. Fahoum, Y. Ungar, E. G. Meyron-Holtz, A. Shpigelman and U. Lesmes, Food Funct., 2018, 9, 1344–1352. Food Funct. 2019;10(3):1760–2. https://doi.org/10.1039/c8fo01282b.CrossRefPubMed

38.

McKim JM, Willoughby JA Sr, Blakemore WR, et al. Clarifying the confusion between poligeenan, degraded carrageenan, and carrageenan: a review of the chemistry, nomenclature, and in vivo toxicology by the oral route. Crit Rev Food Sci Nutr. 2018; https://doi.org/10.1080/10408398.2018.1481822.CrossRefPubMed

39.

Diederich L, Suvorava T, Sansone R, et al. On the effects of reactive oxygen species and nitric oxide on red blood cell deformability. Front Physiol. 2018;9:332. https://doi.org/10.3389/fphys.2018.00332.CrossRefPubMedPubMedCentral

40.

Mohanty JG, Nagababu E, Rifkind JM. Red blood cell oxidative stress impairs oxygen delivery and induces red blood cell aging. Front Physiol. 2014;5:84. https://doi.org/10.3389/fphys.2014.00084.CrossRefPubMedPubMedCentral

Titel: Food additive E407a stimulates eryptosis in a dose-dependent manner
verfasst von: Dr. Anton Tkachenko, MD, PhD
Dr. Yurii Kot, PhD
Dr. Volodymyr Prokopyuk, MD, PhD
Dr. Anatolii Onishchenko, MD, PhD
Dr. Alla Bondareva, PhD
Prof. Valeriy Kapustnik, MD, PhD, DSc
Prof. Tetyana Chumachenko, MD, PhD, DSc
Prof. Yevgen Perskiy, PhD, DSc
Prof. Dmytro Butov, MD, PhD, DSc
Prof. Oksana Nakonechna, MD, PhD, DSc
Publikationsdatum: 12.08.2021
Verlag: Springer Vienna
Erschienen in: Wiener Medizinische Wochenschrift / Ausgabe 5-6/2022
Print ISSN: 0043-5341
Elektronische ISSN: 1563-258X
DOI: https://doi.org/10.1007/s10354-021-00874-2

Springer Medizin Österreich

Summary

Background

Objective

Methods

Results

Conclusion

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