MUTAGENIC PROPERTIES OF THE SUBSTANCE FUCOIDAN

Download full text PDF
DOI: https://doi.org/10.29296/25419218-2018-03-09
Issue: 
3
Year: 
2018

A.Kh. Sharaf(1); E.D. Bondareva(1), K.L. Kryshen(1); O.N. Pozharitskaya(1); E.D. Obluchinskaya(1); M.N. Makarova(1) 1-Saint Petersburg Institute of Pharmacy; 3, Zavodskaya St., Build. 245, Kuzmolovsky Urban-Type Settlement, Vsevolozhsky District, Leningrad Region 188663, Russian Federation; 2-Murmansk Marine Biological Institute, Kola Research Center, Russian Academy of Sciences; 17, Vladimirskaya St., Murmansk 183010, Russian Federation

Introduction. The algal polysaccharide fucoidan is a plant heparin analogue; it does not cause side effects or show related contraindications inherent in heparin. Fucoidan is obtained from the thalli of the brown alga bladderwrack (Fucus vesiculosus L.) in the coastal zone of the Barents Sea. The obligatory part of preclinical trials of new pharmacological agents is mutagenicity testing that provides an assessment of their ability to induce different types of mutations in the embryonic and somatic cells of animals, in the cells of microorganisms. Objective: to investigate the mutagenic properties of the substance fucoidan. Material and methods. Fucoidan isolated from the thalli of the alga bladderwrack was investigated. Its mutagenic properties were studied using the mouse micronucleus test and the Ames test. Statistical analysis was performed using Statistica 10.0 software. Results. The Ames test established that the tested object at concentrations of 1000–0.01 µg/ml had no mutagenic effect on Salmonella typhimurium strains during testing with and without metabolic activation. The micronucleus test showed no mutagenic effect of substance fucoidan at doses of 550 and 2000 mg/kg after intragastric administration. Conclusion. It has been established that the substance fucoidan obtained from the thalli of the brown alga bladderwrack has no genotoxic effect and can be recommended as a safe raw material to design a substance-based drug.
Keywords: 
bladderwrack
Fucus vesiculosus L.
fucoidan
substance
mutagenicity
genotoxicity
micronuclei
Ames test
References: 
  1. Cumashi A., Ushakova N.A., Preobrazhenskaya M.E. et al. A comparative study of the anti-inflammatory, anticoagulant, antiangiogenic, and antiadhesive activities of nine different fucoidans from brown seaweeds. Glycobiology. 2007;17(5): 541–52. DOI: 10.1093/glycob/cwm014.
  2. Ushakova N.A., Morozevich G.E., Ustyuzhanina N.E. i dr. Antikoagulyantnaya aktivnost` fukoidanov iz buryh vodorosley. Biomedicinskaya himiya, 2008; 54. (5): 597–606. [Ushakova N.A., Morozevich G.E., Ustyuzhanina N.E. et. al. Anticoagulant activity of fucoidans from brown algae. Biomeditsinskaya Khimiya, 2008; 54 (5): 597–606 (in Russian)]. DOI: 10.1134/s1990750809010119.
  3. Obluchinskaya E.D. Vliyanie faktorov vneshney sredy na soderzhanie polisaharidov fukusa puzyrchatogo Fucus vesiculosus L. Himiya rastitel`nogo syr`ya, 2011; 3: 47–51. [Obluchinskaya E.D. Influence of environmental factors on the content of polysaccharides of Fucus vesiculosus L. Khimiya Rastitel’nogo Syr’ya, 2011; 3: 47–51 (in Russian)]].
  4. Synytsya A., Kim W.J., Kim S.M., et al. Structure and antitumour activity of fucoidan isolated from sporophyll of Korean brown seaweed Undaria pinnatifida. Carbohydr Polym., 2010; 81 (1): 41–8. DOI: 10.1016/j.carbpol.2010.01.052.
  5. Mironov A.N. Rukovodstvo po provedeniyu doklinicheskih issledovaniy lekarstvennyh sredstv. Ch. 1. M.: Grif i K, 2012. [Mironov A.N. A guide to preclinical drug research. P.1. Moscow: Grif and K; 2012 (in Russian)].
  6. International Conference on Harmonisation; guidance on S2(R1) Genotoxicity Testing and Data Interpretation for Pharmaceuticals intended for Human Use; availability. Notice. Fed Regist., 2012; 77 (110): 33748–9.
  7. Kosman V.M., Obluchinskaya E.D., Pozharickaya O.N., Makarova M.N., Shikov A.N. Skvoznaya standartizaciya substancii fukoidana i preparatov na ee osnove. Farmaciya, 2017; 66 (6): 20–4.[ Kosman V., Obluchinskaya E., Pozharitskaya O., Makarova M., Shikov A.N. Through standardization of the substance fucoidan and its based preparations. Farmatsiya, 2017; 66 (6): 20–4 (in Russian)].
  8. Acapkina A.A., Kryshen` K.L., Makarova M.N., Makarov V.G. Primenenie bakterial`nyh test-sistem dlya ocenki potencial`nogo mutagennogo e`ffekta novyh farmacevticheskih soedineniy. Mezhdunarodnyy vestnik veterinarii, 2014; 2: 109–13. [Atsapkina A.A., Kryshen K.L., Makarova M.N., Makarov V.G. Application of bacterial test systems to assess the potential mutagenic effect of new pharmaceutical compounds. Mezhdunarodny vestnik veterinarii. 2014; 2: 109–13 (in Russian)].
  9. Barnes W., Tuley E., Eisenstadt E. Base-sequence analysis of His+ revertants of the hisG46 missense mutation in Salmonella typhimurium. Environ Mutagen., 1982; 4 (3): 297.
  10. Ames B.N., Lee F.D., Durston W.E. An improved bacterial test system for the detection and classification of mutagens and carcinogens. Proc. Natl. Acad. Sci. USA. 1973; 70: 782–6.
  11. Belicikiy G.A., Hudoley V.V. Kratkosrochnye testy v sisteme vyyavleniya kancerogennyh dlya cheloveka himicheskih soedineniy. Voprosy onkologii, 1998; 32 (4): 1–3. [Belitsky G.A., Khudoley V.V. Short-term tests in a system for the detection of human carcinogenic chemicals.Voprosi onkologii. 1998; 32 (4): 1–3 (in Russian)].
  12. Abilev S.K. Osnovnye klassy himicheskih soedineniy, mutagennoe deystvie kotoryh svyazano s aktivnost`yu ih metabolitov. Itogi nauki i tehniki. Seriya: Obshhaya genetika. M.: VINITI, 1988; Vyp. 9. [Abilev S.K. The main classes of chemical compounds whose mutagenic action is related to the activity of their metabolites.The results of science and technology. A series of general genetics. Moscow: VINITI; 1988; 9 (in Russian.)].
  13. Rybakova A. V., Makarova M. N. Metody e`vtanazii laboratornyh zhivotnyh v sootvetstvii s Evropeyskoy direktivoy 2010/63. Mezhdunarodnyy vestnik veterinarii, 2015; 2: 96–107. [Rybakova A., Makarova M. Methods of euthanasia of laboratory animals, in accordance with European Directive 2010/63. Mezhdunarodny vestnik veterinarii., 2015; 2: 96–107 (in Russian)].
  14. Li B., Lu F., Wei X., Zhao R. Fucoidan: structure and bioactivity. Molecules, 2008;13 (8):1671–95. DOI: 10.3390/molecules13081671.
  15. Chung H.J., Jeun J., Houng S.J. et al. Toxicological evaluation of fucoidan from Undaria pinnatifida in vitro and in vivo. Phytotherapy research., 2010; 24 (7): 1078–83. DOI: 10.1002/ptr.3138.
  16. Kim K.J., Lee O.H., Lee B.Y. Genotoxicity studies on fucoidan from Sporophyll of Undaria pinnatifida. Food and chemical toxicology, 2010; 48 (4): 1101–4. DOI: 10.1016/j.fct.2010.01.032.
  17. Hwang P.A., Yan M.D., Lin H.T. et al. Toxicological evaluation of low molecular weight fucoidan in vitro and in vivo. Mar. Drugs, 2016;14 (7):121. DOI: 10.3390/md14070121.
  18. Li N., Zhanq Q., Song J. Toxicological evaluation of fucoidan extracted from Laminaria japonica in Wistar rats. Food and Chemical Toxicology, 2005; 43 (3): 421–6. DOI: 10.1016/j.fct.2004.12.001.