Laboraroty Animal Research

Korean Association for Laboratory Animal Science (한국실험동물학회)
권호 표지

Single Subcutaneous Dose Toxicity of $Polycan^{\circledR}$, a $\beta$-Glucan Originated from Aureobasidium in Mice

Lee, Jae-Hyun;Yang, Kun-Ju;Shin, Hyun-Dong;Park, Bok-Ryeon;Son, Chang-Woo;Jang, Hee-Jeong;Park, Dong-Chan;Lee, Hyeung-Sik;Ku, Sae-Kwang

  • Published : 20051200
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Abstract

This study was conducted to obtain the acute information of the subcutaneous dose toxicity of Polycan-originated from Aureobasidium pullulans SM-2001 (half of the dry material is $\beta$-1,3/1,6-glucans), having various pharmacological effects, in mice. Test articles were once subcutaneously administered to mice at dose levels of 250, 125 and 62.5 mg/kg. The mortality and changes on body weight, clinical signs and gross observation were monitored during 14 days after dosing. As the results, we could not find mortalities, clinical signs and changes in the body weight except for residuals of test articles and related skin ulcer at injection sites. Hypertrophy of spleen related to the immune modulate effect of Polycan was dose-dependently detected in all dosing groups tested as gross findings, and hyperplasia of lymphatic follicles and increase of number of megakaryocytes in red pulps are dose-dependently observed at histopathological observation of spleen. In addition, infiltration of inflammatory cells in residuals of test articles in injection site were dose dependently detected with skin ulcer in some animals restricted to these injection sites. The skin ulcer detected in the present study was considered to be biting wounds. The results obtained in this study suggest that the Polycan have no systemic toxicity in mice and is therefore likely to be safe for clinical use. The median lethal dose (L$D_{50}$) and approximate lethal dose in mice after single subcutaneous dose of Polycan were considered over 250 mg/kg, the highest dissolved concentration in distilled water respectively.

Keywords

References

  1. Bais, D., Trevisan, A., Lapasin, R., Partal, P. and Gallegos, C. (2005) Rheological characterization of polysaccharide-surfactant matrices for cosmetic O/W emulsions. J. Colloid Interface Sci. 290, 546-556 https://doi.org/10.1016/j.jcis.2005.04.044
  2. Bell, S., Goldman,V.M., Bistrian, B.R.. Arnold, A.H., Ostroff, G. and Forse, R.A. (1999) Effect of beta-glucan from oats and yeast on serum lipids. Crit. Rev. Food Sci. Nutr. 39, 189-202 https://doi.org/10.1080/10408399908500493
  3. Bourdon, I., Yokoyama, W., Davis. P., Hudson, C., Backus, R., Richter, D., Knuckles. B. and Schneeman, B.O. (1999) Postprandial lipid, glucose, insulin, and cholecystokinin responses in men fed barley pasta enriched with beta-glucan. Am. J. Clin. Nutr: 69, 55-63
  4. Braaten. J.T., Scott. F.W., Wood, P.J., Riedel, K.D., Wolynetz, M.S., Brule, D. and Collins. M.W. (1994) High beta-glucan oat bran and oat gum reduce postprandial blood glucose and insulin in subjects with and without type 2 diabetes. Diabet. Med. 11, 312-318 https://doi.org/10.1111/j.1464-5491.1994.tb00277.x
  5. Chihara, G. (1983) Preclinical evaluation of lentinan in animal models. Adv. Exp. Med. Biol. 166, 189-197
  6. Czop, J.K. (1986) The role of beta-glucan receptors on blood and tissue leukocytes in phagocytosis and metabolic activation. Pathol. Immunopathol. Res. 5, 286-296 https://doi.org/10.1159/000157022
  7. Delaney, B., Carlson, T., Zheng, G.H., Hess, R., Knutson, N., Frazer, S., Ostergren, K., van Zijverden, M., Knippels, L., Jonker, D. and Penninks, A. (2003) Repeated dose oral toxicological evaluation of concentrated barley beta-glucan in CD-I mice including a recovery phase. Food Chem. Toxicol. 41, 1089-1102 https://doi.org/10.1016/S0278-6915(03)00046-2
  8. Dourish, C.T. (1987) Effects of drugs on spontaneous motor activity. In Experimental Psychopharmacology (Greenshaw, A.J. and Dourish, C.T. Eds), pp.325-334, Humana Press, Clifton
  9. Eppley, B.L., Summerlin, D.J., Prevel, C.D. and Sadove, A.M. (1994) Effects of a positively charged biomaterial for dermal and subcutaneous augmentation. Aesthetic Plast. Surg. 18, 413-416 https://doi.org/10.1007/BF00451350
  10. Estrada, A., Yun, C.H., Van Kessel, A., Li, B., Hauta, S. and Laarveld, B. (1997) Immunomodulatory activities of oat betaglucan in vitro and in vivo. Microbiol. Immunol. 41, 991-998
  11. Feletti, F., De Bernardi di Valserra, M., Contos, S., Mattaboni, P. and Germogli, R. (1992) Chronic toxicity study on a new glucan extracted from Candida albicans in rats. Arzneimittelforschung 42, 1363-1367
  12. Gu, Y.H., Takagi, Y., Nakamura, T., Hasegawa, T., Suzuki, I., Oshima, M., Tawaraya, H. and Niwano, Y. (2005) Enhancement of radioprotection and anti-tumor immunity by yeast-derived beta-glucan in mice. J. Med. Food 8, 154-158 https://doi.org/10.1089/jmf.2005.8.154
  13. Hodge, H.C. and Sterner, J.H. (1949) Tabulation of toxicity classes. Am. Ind. Hyg. Q. 10, 93
  14. Iqbal, M.P., Sultana, F., Mehboobali, N. and Pervez, S. (2001) Folinic acid protects against suppression of growth by methotrexate in mice. Biopharm. Drug Dispos. 22, 169-178 https://doi.org/10.1002/bdd.271
  15. Irwin, S. (1968) Comprehensive observational assessment: la. A systemic, quantitative procedure for assessing the behavioral and physiological state of the mouse. Psychopharmacology 13, 222-257 https://doi.org/10.1007/BF00401402
  16. Kenyon, A.J. (1983) Delayed wound healing in mice associated with viral alteration of macrophages. Am. J. Vet. Res. 44, 652-656
  17. Klein, H.O., Kreysch, H.G., Coerper, C., Voigt, P. and Ruff, 1. (1987) Preclinical and early clinical trial with mafosfamide as immune modulator. Methods Find Exp. Clin. Pharmacol. 9, 627-640
  18. Korea Food and Drug Administration (1999) Testing Guidelines for Safety Evaluation of Drugs (Notification No. 1999-61, issued by the Korea Food and Drug Administration on December 22, (1999)
  19. Lejeune, F.J., Vercammen-Grandjean, A., Mendes da Costa, P., Bron, D. and Defleur, V. (1979) Suppressor cell induction and reticuloendothelial cells activation produced in the mouse by beta 1-3 glucan. Adv. Exp. Med. Biol. 121, 235-244
  20. Lia, A., Hallmans, G., Sandberg, A.S., Sundberg, B., Aman, P. and Andersson, H. (1995) Oat beta-glucan increases bile acid excretion and a fiber-rich barley fraction increases cholesterol excretion in ileostomy subjects. Am. J. Clin. Nutr. 62, 1245-1251
  21. Pelizon, A.C., Kaneno, R., Soares, A.M., Meira, D.A. and Sartori, A. (2003) Down-modulation of lymphoproliferation and interferon-gamma production by beta-glucan derived from Saccharomyces cerevisiae. Mem. Inst. Oswaldo Cruz. 98, 1083-1087 https://doi.org/10.1590/S0074-02762003000800019
  22. Seo, H.P., Kim, J.M., Shin, H.D., Kim, T.K., Chang, H.J., Park, B.R. and Lee J.W. (2002) Production of $\beta$-1,3/1,6-glucan by Aureobasidium pullulans SM-2001. Korean J. Bitechnol. Bioeng. 17, 376-380
  23. Spicer, E.J., Goldenthal, E.I. and Ikeda, T. (1999) A toxicological assessment of curdlan. Food Chem. Toxicol. 37, 455-479 https://doi.org/10.1016/S0278-6915(99)00013-7
  24. Tong, D.W. and Barnetson, R.S. (1996) Beta-1,3-D-glucan gel in the treatment of solar keratoses. Australas J. Dermatol. 37, 137-138 https://doi.org/10.1111/j.1440-0960.1996.tb01031.x
  25. Trabucchi, E., Pallotta, S., Morini, M., Corsi, F., Franceschini, R., Casiraghi, A., Pravettoni, A., Foschi, D. and Minghetti, P. (2002) Low molecular weight hyaluronic acid prevents oxygen free radical damage to granulation tissue during wound healing. Int. J. Tissue React. 24, 65-71
  26. US Environmental Protection Agency (1998) Health Effects Test Guidelines OPPTS 870.100. Acute Toxicity Testing Background. US EPA August, Washington, USA
  27. Williams, D.L., Sherwood, E.R., Browder, I.W., McNamee, R.B., Jones, E.L. and Di Luzio, N.R. (1988) Pre-clinical safety evaluation of soluble glucan. Int. J. Immunopharmacol. 10, 405-414 https://doi.org/10.1016/0192-0561(88)90127-0
  28. Wolk, M. and Danon, D. (1985) Promotion of wound healing by yeast glucan evaluated on single animals. Med. Biol. 63, 73-80
  29. Yan, J., Allendorf, D.J. and Brandley, B. (2005) Yeast whole glucan particle (WGP) beta-glucan in conjunction with antitumour monoclonal antibodies to treat cancer. Expert Opin. Biol. Ther. 5, 691-702 https://doi.org/10.1517/14712598.5.5.691
  30. Yan, J., Zong, H., Shen, A., Chen, S., Yin, X., Shen, X., Liu, W., Gu, X. and Gu, J. (2003) The bera-(I$\rightarrow$6)-branched beta-(I$\rightarrow$3) glucohexaose and its analogues containing an alpha-(I$\rightarrow$3)-linked bond have similar stimulatory effects on the mouse spleen as Lentinan. Int. J. Immunopharmacol. 3, 1861-1871 https://doi.org/10.1016/j.intimp.2003.09.003