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. 2008 Mar 1;24(1):79–86. doi: 10.5487/TR.2008.24.1.079

Oral Single Dose Toxicity Study of Low Molecular Fucoidan in Mice

Young-Mi Jung 111, Kang Min Yoo 211, Dong-Chan Park 111, Tae-Kwon Kim 111, Hyeung-Sik Lee 311, Sae-Kwang Ku 411,511,
PMCID: PMC7006321  PMID: 32038780

Abstract

This study was conducted to obtain information of the oral dose toxicity of low molecular fucoidan (LMF) in male and female mice. In order to calculate 50% lethal dose (LD50) and approximate lethal dose (LD), test material was once orally administered to male and female ICR mice at dose levels of 2000, 1000, 500, 250, 125 and 0 (vehicle control) mg/kg (body wt.). The mortality and the changes on body weight, clinical signs, gross observation and organ weight and histopathology of principle organs were monitored 14 days after LMF treatment. We could not find any mortalities, clinical signs, body weight changes and gross findings. In addition, significant changes in the organ weight and histopathology of principal organs were not observed except for some sporadic findings. The results obtained in this study suggest that LMF may not be toxic in mice and may be therefore safe for clinical use. The LD50 and approximate LD in mice after single oral dose of LMF were considered over 2000 mg/kg in both female and male mice.

Key words: Low molecular fucoidan, Single oral dose toxicity, Mice, Histopathology

References

  1. Alkhatib B, Freguin-Bouilland C, Lallemand F, Henry JP, Litzler PY, Marie JP, Richard V, Thuillez C, Plissonnier D. Low molecular weight fucan prevents transplant coronaropathy in rat cardiac allograft model. Transpl. Immunol. 2006;16:14–19. doi: 10.1016/j.trim.2006.03.003. [DOI] [PubMed] [Google Scholar]
  2. Banks, W.J. (1986). Female reproductive system in Applied veterinary histology (Banks, W.J. Ed.). Williams & Wilkins, Baltimore, pp. 506–526.
  3. Béress A, Wassermann O, Tahhan S, Bruhn T, Beress L, Kraiselburd EN. A new procedure for the isolation of anti-HIV compounds (polysaccharide and polyphenols) from the marine algae Fucus vesiculosus. J. Nat. Prod. 1993;56:478–488. doi: 10.1021/np50094a005. [DOI] [PubMed] [Google Scholar]
  4. Berteau O, Mulloy B. Sulfated fucans, fresh perspectives: structures, functions, and biological properties of sulfated fucans and an overview of enzymes active toward this class of polysaccharide. Glycobiology. 2003;13:29R–40R. doi: 10.1093/glycob/cwg058. [DOI] [PubMed] [Google Scholar]
  5. Blondin C, Chaubet F, Nardella A, Sinquin C, Jozefonvicz J. Relationships between chemical characteristics and anticomplementary activity of fucans. Biomaterials. 1996;17:597–603. doi: 10.1016/0142-9612(96)88710-2. [DOI] [PubMed] [Google Scholar]
  6. Bojakowski K, Abramczyk P, Bojakowska M, Zwolinska A, Przybylski J, Gaciong Z. Fucoidan improves the renal blood flow in the early stage of renal ischemia/reperfusion injury in the rat. J. Physiol. Pharmacol. 2001;52:137–143. [PubMed] [Google Scholar]
  7. Colliec S, Fischer AM, Tapon-Bretaudiere J, Boisson C, Durand P, Jozefonvicz J. Anticoagulant properties of a fucoidan fraction. Thromb. Res. 1991;64:143–154. doi: 10.1016/0049-3848(91)90114-C. [DOI] [PubMed] [Google Scholar]
  8. Dourish, C.T. (1987). Effects of drugs on spontaneous motor activity in Experimental Psychopharmacology (Greenshaw, A.J. and Dourish, C.T. Eds.). Humana Press, Clifton, pp. 325–334.
  9. Dubois M, Gilles KA, Hamilton JK, Rebers PA, Smith F. Colorimetric method for determination of sugars and related substances. Anal. Chem. 1956;28:350–354. doi: 10.1021/ac60111a017. [DOI] [Google Scholar]
  10. Farndale RW, Buttle DJ, Barret AJ. Improved quantification and discrimination of sulphated glycosaminoglycans by use of dimethylmethylene blue. Biochim. Biophys. Acta. 1986;883:173–177. doi: 10.1016/0304-4165(86)90306-5. [DOI] [PubMed] [Google Scholar]
  11. Fréguin-Bouilland C, Alkhatib B, David N, Lallemand F, Henry JP, Godin M, Thuillez C, Plissonnier D. Low molecular weight fucoidan prevents neointimal hyperplasia after aortic allografting. Transplantation. 2007;83:1234–1241. doi: 10.1097/01.tp.0000261109.97928.9c. [DOI] [PubMed] [Google Scholar]
  12. Haroun-Bouhedja F, Ellouali M, Sinquin C, Boisson-Vidal C. Relationship between sulfate groups and biological activities of fucans. Thromb. Res. 2000;100:453–459. doi: 10.1016/S0049-3848(00)00338-8. [DOI] [PubMed] [Google Scholar]
  13. Hodge Harold C., Sterner James H. Tabulation of Toxicity Classes. American Industrial Hygiene Association Quarterly. 1949;10(4):93–96. doi: 10.1080/00968204909344159. [DOI] [PubMed] [Google Scholar]
  14. Irwin S. Comprehensive observational assessment: Ia. A systemic, quantitative procedure for assessing the behavioral and physiological state of the mouse. Psychopharmacology. 1968;13:222–257. doi: 10.1007/BF00401402. [DOI] [PubMed] [Google Scholar]
  15. Jung YM, Kim TK, Park DC, Lee YH. Bioavailable Fucoidan and Methods for Preparing the Same. 2007. [Google Scholar]
  16. Korea FoodDrug Administration. Testing Guidelines for Safety Evaluation of Drugs. 2005. [Google Scholar]
  17. Lake AC, Vassy R D, Benedetto M, Lavigne D L, Visage C, Perret GY, Letourneur D. Low molecular weight fucoidan increases VEGF165-induced endothelial cell migration by enhancing VEGF165 binding to VEGFR-2 and NRP1. J. Biol. Chem. 2006;281:37844–37852. doi: 10.1074/jbc.M600686200. [DOI] [PubMed] [Google Scholar]
  18. Lee HS, Lee IG, Ku SK. Single oral dose toxicity study of water extracts of Picrorrhiza Rhizoma in mice. J. Toxicol. Pub. Health. 2006;22:117–126. [Google Scholar]
  19. Lee HS, Yang KJ, Shin HD, Park BR, Son CW, Jang HJ, Park DC, Jung YM, Ku SK. Single oral dose toxicity study of polycan, β-glucan originated from Aureobasidium in mice. J. Toxicol. Pub. Health. 2005;21:361–365. [Google Scholar]
  20. Lee YH, Son MK, Jung YM, Kim TK, Park DC, Lee HS, Kim PS, Ku SK. Mouse single oral dose toxicity studies of PGB-1, a novel polyglucosamine polymer produce from Enterobacter sp. BL-2. J. Toxicol. Pub. Health. 2007;23:373–382. [Google Scholar]
  21. Li N, Zhang Q, Song J. Toxicological evaluation of fucoidan extracted from Laminaria japonica in Wistar rats. Food Chem. Toxicol. 2005;43:421–426. doi: 10.1016/j.fct.2004.12.001. [DOI] [PubMed] [Google Scholar]
  22. Marais MF, Joseleau JP. A fucoidan fraction from Ascophyllum nodosum. Carbohydr. Res. 2001;336:155–159. doi: 10.1016/S0008-6215(01)00257-9. [DOI] [PubMed] [Google Scholar]
  23. Matsubara K, Xue C, Zhao X, Mori M, Sugawara T, Hirata T. Effects of middle molecular weight fucoidans on in vitro and ex vivo angiogenesis of endothelial cells. Int. J. Mol. Med. 2005;15:695–699. [PubMed] [Google Scholar]
  24. Nardella A, Chaubet F, Sinquin C C, Jouault S, Boisson-Vidal C, Durand P, Jozefonvicz J. Method for Obtaining Sulfated Polysaccharides, United States Patent 6,028,191. 2000. [Google Scholar]
  25. Organization for Economic Co-OperationDevelopment. OECD guideline (423) for testing of chemicals-acute oral toxicity-acute toxic class method. 2001. [Google Scholar]
  26. Patankar MS, Oehninger S, Barnett T, Williams RL, Clark GF. A revised structure for fucoidan may explain some of its biological activities. J. Biol. Chem. 1993;268:21770–21776. [PubMed] [Google Scholar]
  27. Plata EJ, Murphy WH. Growth and haematologic properties of the BALB/wm strain of inbred mice. Lab. Anim. Sci. 1972;22:712–720. [PubMed] [Google Scholar]
  28. Senni K, Gueniche F, Foucault-Bertaud A, Igondjo-Tchen S, Fioretti F, Colliec-Jouault S, Durand P, Guezennec J, Godeau G, Letourneur D. Fucoidan a sulfated polysaccharide from brown algae is a potent modulator of connective tissue proteolysis. Arch. Biochem. Biophys. 2006;445:56–64. doi: 10.1016/j.abb.2005.11.001. [DOI] [PubMed] [Google Scholar]
  29. Shimizu J, Wada-Funada U, Mano H, Matahira Y, Kawaguchi M, Wada M. Proportion of murine cytotoxic T cells is increased by high molecular-weight fucoidan extracted from Okinawa mozuku (Cladosiphon okamuranus) J. Health Sci. 2005;51:394–397. doi: 10.1248/jhs.51.394. [DOI] [Google Scholar]
  30. US Environmental Protection Agency. Health Effects Test Guidelines OPPTS 870.100, Acute Toxicity Testing Background. USA: US EPA August, Washington; 1998. [Google Scholar]
  31. Yamaguchi C, Fujita S, Obara T, Ueda T. Effects of room temperature on reproduction, body weight and organ weights, food and water intakes, and hematology in mice. Exp. Anim. 1983;32:1–11. doi: 10.1538/expanim1978.32.1_1. [DOI] [PubMed] [Google Scholar]
  32. Zemani F, Benisvy D, Galy-Fauroux I, Lokajczyk A, Colliec-Jouault S, Uzan G, Fischer AM, Boisson-Vidal C. Low-molecular-weight fucoidan enhances the proangiogenic phenotype of endothelial progenitor cells. Biochem. Pharmacol. 2005;70:1167–1175. doi: 10.1016/j.bcp.2005.07.014. [DOI] [PubMed] [Google Scholar]

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