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Archives of Pharmacal Research

, Volume 28, Issue 9, pp 1079–1085 | Cite as

Chitosan Oligosaccharide inhibits203HgCl2-induced genotoxicity in mice: Micronuclei occurrence and chromosomal aberration

  • Hyun Joong Yoon
  • Haeng Soon Park
  • Hee-Seung Bom
  • Young Bok Roh
  • Jong Se Kim
  • Young Ho KimEmail author
Articles Drug Development

Abstract

The purpose of this study was to investigate the safety of chitosan oligosaccharide and the effects of chitosan oligosaccharide on mercury induced genotoxicity in mice using the micronuclei and chromosome aberration. The micronuclei test was performed by microscopic examination (×1,000, stained using a May-Grunwald solution) after administering 0.01, 0.1, and 1% (10 mg/mL) chitosan oligosaccharide for 7, 60, and 180 daysad libitum in mice. Total micronuclei of 1,000 polychromatic erythrocytes were recorded for each group. There was no difference between the untreated and experimental groups. The intake periods and concentrations of chitosan oligosaccharide did not affect the occurrence of micronuclei in bone marrow cells (P>0.05). The chromosomal aberration test was performed by microscopic examination (×1,000, stained using a 4% Giemsa solution) after administering the same concentration of chitosan oligosaccharide to mice, in F1, F2, F3 generations and parents. The frequency of chromosomal aberrations was defined as [Ydr=(D+R)/total number of counted lymphocytes]. Similar to the micronuclei test, there was no difference between the untreated and treated groups. These results showed that the intake periods and concentrations of chitosan oligosaccharide did not affect chromosomal aberrations in bone marrow cells (P>0.05). To investigate the effect of chitosan oligosaccharide on mercury-induced chromosome aberration, mice in each condition were supplied with203HgCl2 and chitosan oligosaccharidead libitum. Chitosan oligosaccharide significantly inhibited203HgCl2-induced chromosome aberration in mice. Based on the results of this study, it may be concluded that the chitosan oligosaccharide is a nontoxic material that could be used as a suppressor of heavy metal-induced genotoxicity.

Key words

Chitosan oligosaccharide Mercury Micronucleus Chromosomal aberration 

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References

  1. Bala, K. V. C., and Rao, K. P., Inhibition of methyl mercury chloride-induced chromosomal damage by gamma-linonelic acid.Fed. Chem. Toxic, 31, 431–434 (1993).CrossRefGoogle Scholar
  2. Darina, C., and Jozef, S., Effect of carboxymethyl-chitin-glucan on cyclophosphamide induced mutagenicity.Mutation Research, 346, 43–48 (1995).CrossRefGoogle Scholar
  3. Fenench, M., and Morley, A. A., Measurement of micronuclei in lymphocyte.Mutation Research, 147, 29–36 (1985).Google Scholar
  4. Garcia, C. L., Darroudi, F., Tates, A. D., and Natarajan, A. T., Induction and presistence of micronuclei, sister-chromatid exchanges and chromosomal aberrations in splenocytes and bone-marrow cells of rats exposed to ethylene oxide.Mutation Research, 492, 59–67 (2001).Google Scholar
  5. Goncharova, R., Zabrejko, S., Dalivelya, O., and Kuzhir, T., Anticlastogenecity of two derivatives of 1,4-dihydroisonicotinic acid in mouse micronucleus test.Mutation Research, 496, 129–135 (2001).PubMedGoogle Scholar
  6. Guadano, A., Coloma, A. G., and Pena, E., Genotoxicity of the insecticide rotenone in cultured human lympocytes.Mutation Research, 414, 1–7 (1998).PubMedGoogle Scholar
  7. Heddle, J. A., A rapidin vivo test for chromosome damage.Mutation Research, 18, 187–190 (1973).PubMedGoogle Scholar
  8. Hirano, S. M., Iwata, K., Nakayama, H., and Toda, H., Enhancement of serum lysozyme activity by injecting a mixture of chitosan oligosaccharides intravenously in rabbit.Agric. Biol. Chem., 55, 2623–2625 (1991).Google Scholar
  9. Jagetia, G. C., and Aruna, R., Effects of various concentration of acyclovir on cell survival and micronuclei induction on cultured HeLa cells.Mutation Res., 446, 155–165 (1999).PubMedGoogle Scholar
  10. Kim, J. H., Yoo, K. J., Song, H. C., and Kim, H. K., Antiparasitic effects of chitosan oligosaccharide against scuticociliatids collected from japanese flounder, Paralichtys olivaceus.Kor. J. Chitin Chitosan, 6, 47–52 (2001).Google Scholar
  11. Kim, Y. H., Bom, H. S., Kim, K. Y., Kim, H. K., and Kim, J. Y., Inhibitory effect of chitosan on the milk transfer of radiostrontium from contaminated mice to their sucklers.Kor. J. Chitin Chitosan, 4, 15–18 (1999).Google Scholar
  12. Kim, Y. H., Bom, H. S., Kim, J. Y., and Roh, Y. B., The effect of calcium and chitosan metabolism to the excretion of radiostrontium in mice.J. Kor. Asso. Radiat. Prot., 22, 9–14 (1997).Google Scholar
  13. Koga, D., Induction of chitinase for plant self-defense.Chitin/Chitosan symposium, in Japan Chitin/Chitosan Res., 4–26 (1993).Google Scholar
  14. Lawrence, J. N., and Benford, D. J., Detection of chemical-induced unscheduled DNA synthesis in cultures of normal adult human keratinoctes.Toxic In Vitro, 5, 377–381 (1991).CrossRefGoogle Scholar
  15. Ledebur, M. V., and Schmid, W., The micronucleus test methodological aspects.Mutation Res., 19, 109–117 (1973).Google Scholar
  16. Lin, W., Xue, H., Liu, S., He, Y., Fu, J., and Zhou, Z., Genotoxicity of nitric oxide produced from sodium nitroprusside.Mutation Res., 413, 121–127 (1998).PubMedGoogle Scholar
  17. Natarajan, A. T., and Obe, G., Molecular mechanisms involved in the production of chromosomal aberrations.Chromosome, 90, 120–127 (1984).CrossRefGoogle Scholar
  18. Nishimura, Y., Kim, S. H., Ikota, N., Arima, H., Bom, H. S., Kim, Y. H., Watanabe, Y., Yukawa, M., and Ozawa, T., Radioprotective effect of chitosan in sub-lethally X-ray irradiated mice.J. Radiat. Res., 44, 53–58 (2003).PubMedCrossRefGoogle Scholar
  19. Okamoto, Y., Ohmi, H., Minami, S., Muhashi, A., Shigemasa, Y., Okumura, M., and Fujinaga, T., Anti-tumor effect of chitin and chitosan on canine transmissible sarcoma.Chitin/Chitosan symposium, in Japan Chitin/Chitosan Res., 1, 76–77 (1995).Google Scholar
  20. Padovani, L., Tronati, L., Mauro, F., Testa, A., Appolloni, M., Azzidei, P., Capprossi, D., Tedeschi, B., and Vernole, P., Cytogenetic effects in lymphocytes from children exposed to radiation fall-out after the chernobyl accident.Mutation Res., 395, 249–254 (1997).PubMedGoogle Scholar
  21. Ramalho, A., Sunjevaric, I., and Natarajan, A. T., Use of the frequencies of micronuclei as quantitative indicators of X-ray-induced chromosomal aberration in human peripheral blood lymphocytes: Comparison of the method.Mutation Res., 207, 141–146 (1988).PubMedCrossRefGoogle Scholar
  22. Rauscher, R., Edenharber, R., and Platt, K. L.,In vitro antimutagenic andin vivo anticlastogenic effects of carotenoids and solvent extracts from fruits and vegetables rich in carotenoids.Mutation Res., 41, 129–142 (1998).Google Scholar
  23. Robbiano, R., Mereto, E., Morando, A. M., and Brambilla, G., Increased frequency of micronucleated kidney cells in rats exposed to halogenated anaesthetic.Mutation Res., 413, 1–6 (1998).PubMedGoogle Scholar
  24. Romm, H., and Stwphan, G., Chromosome analysis-a routine method for quantitative radiation dose assessment.Kemtechnik, 55(4), 219–225 (1990).Google Scholar
  25. Schmid, M., The micronucleus test.Mutation Res., 31, 9–15 (1975).PubMedGoogle Scholar
  26. Skjak, G., Anthonsen, T., and Sandford P., The use of chitosan in cosmetics. In Chitin and chitosan: Sources, chemistry, biochemistry, physical properties and applications. Elsevier, Applied science, pp. 139–147, (1998).Google Scholar
  27. Stacher, A., Ruzicka, H., and Schuhfried, G., Chromosomal aberration due to cytostatic agents.Int. J. Clin. Pharmacol., 9, 250–257 (1974).PubMedGoogle Scholar
  28. Stoiber, T., Bonacker, D., Boöhm, K. J., Bolt, H. M., Their, R., Degen, G. H., and Unger, E., Disturbed microtubule function and induction of micronuclei by chelate complexes of mercury(II).Mutation Res., 563, 97–106 (2004).PubMedGoogle Scholar
  29. Sudharsan, A., and Heddle, J. A., Simultaneous detection of chromosomal aberration and sister-chromatid exchanges: Experience with DNA intercalating agents.Mutation Res., 78, 253–260 (1980).CrossRefGoogle Scholar
  30. Thier, R., Bonacker, D., Stoiber, T., Böhm, K. J., Wang, M., Unger, E., Bolt, H. M., and Degen, G., Interaction of metal salts with cytoskeletal motor protein systems.Toxicol. Lett., 140–141, 75–81 (2003).PubMedCrossRefGoogle Scholar
  31. Tokura, S., Miura, Y., Kaneda, Y., and Uraki, Y., Drug delivery system using biodegradable carrier. Annual Report, Chitin/Chitosan Res., pp. 314–324, (1992).Google Scholar
  32. Tsurutani, R., Yoshimura, M., Tanimoto, N., Hasegawa, A., and Kifune, K., Clinical application of chitin materials to ulcers.Chitin/Chitosan symposium, in Japan Chitin/Chitosan Res., 1, 78–79 (1995).Google Scholar
  33. Wakata, A., and Sasaki, M. S., Measurement of micronuclei by cytochalasin-block method in cultured chinese hamster cells: Comparison with types and rates of chromosome aberration.Mutation Res., 190, 51–57 (1987).PubMedCrossRefGoogle Scholar
  34. Wolff, S. Biological dosimetry with cytogenetic endopints.New Horizons in Biological Dosimetry, 351–362 (1991).Google Scholar
  35. Yoon, H. J., Kim, Y. H., Park, S. W., Lee, H. B., and Park, H. S., Chitosan increases the release of renal dipeptidase from porcine renal proximal tubule cells.Korean J. Biol. Sci., 7, 309–315 (2003).Google Scholar
  36. Yoon, H. J., Kim, Y. H., Lee, H. B., Lee, J. H., and Park, H. S., Study of chitosan on fibroblast growth factor 2 (bFGF) from the renal proximal tubular cells.J. Chitin Chitosan, 9(3), 114–118 (2004).Google Scholar
  37. Yoon, H. J., Park, H. S., Kim, J. S., Choi, Y. B., Roh, Y. B., Lee, J. H., Bom, H. S., and Kim, Y. H., Chelation effects of chitosan on radiomercury (203HgCl2) in mice.J. Chitin Chitosan, 10(2), 61–66 (2005).Google Scholar

Copyright information

© The Pharmaceutical Society of Korea 2005

Authors and Affiliations

  • Hyun Joong Yoon
    • 3
    • 4
  • Haeng Soon Park
    • 3
    • 4
  • Hee-Seung Bom
    • 1
  • Young Bok Roh
    • 2
  • Jong Se Kim
    • 2
  • Young Ho Kim
    • 3
    • 4
  1. 1.Department of Nuclear MedicineChonnam University HospitalGwangjuKorea
  2. 2.Department of Biology, College of Natural ScienceChosun UniversityGwangjuKorea
  3. 3.College of PharmacyChonnam National UniversityGwangjuKorea
  4. 4.Research Institute of Drug DevelopmentChonnam National UniversityGwangjuKorea

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