Molecular & Cellular Toxicology

The Korean Society of Toxicogenomics and Toxicoproteomics (대한독성유전 단백체학회)
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Study on Genotoxicity of Crocin, a Component of Gardenia Fruit, in Bacterial and Mammalian Cell Systems

  • Choi, Hae-Yeon (Department of Food and Nutrition, Sookmyung women's University) ;
  • Kim, Youn-Jung (Cellular and Molecular Toxicology Laboratory, Korea Institute of Science and Technology) ;
  • Jeon, Hee-Kyung (Cellular and Molecular Toxicology Laboratory, Korea Institute of Science and Technology) ;
  • Ryu, Jae-Chun (Cellular and Molecular Toxicology Laboratory, Korea Institute of Science and Technology)
  • Published : 2008.12.31
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Abstract

Crocin is one of the major components of gardenia fruit and saffron which are widely used as natural food colorants and as traditional Chinese medicines. However, the genotoxicity data on crocin are not sufficient for safety evaluation. The purpose of this study was the examination of the genotoxicity on crocin from gardenia yellow in bacterial and mammalian cells, using various genotoxic battery testing assays and the influence of crocin on methyl methanesulfonate (MMS) and ${H_2}{O_2}$-induced DNA damage in vitro, using single cell gel electrophoresis (comet) assay. From results, no considerable mutagenicity and clastogenicity were seen in bacteria and mammalian cells treated with crocin, by Ames test, chromosomal aberration assay, ${tk}^{+/-}$ gene forward mutation assay and comet assay. And, post-treatment with crocin significantly suppressed ${H_2}{O_2}$-induced DNA damage in a dose-dependent manner. In conclusion, the findings of the present study and other previous observations indicate that crocin has no genotoxic potential. And it showed that crocin clearly repressed the genotoxic potency of ${H_2}{O_2}$. These results suggest that anti-oxidative effects of crocin may be involved in the protective effects of DNA damage.

Keywords

References

  1. Rios, J. L., Recio, M. C., Ginger, R. M. & Manz, S. An update review of saffron and its active constituents. Phytother Res 10:189-193 (1996) https://doi.org/10.1002/(SICI)1099-1573(199605)10:3<189::AID-PTR754>3.0.CO;2-C
  2. Abdullaev, F. I. & Espinosa-Aguirre, J. J. Biomedical properties of saffron and its potential use in cancer therapy and chemoprevention trials. Cancer Detect Prev 28:426-432 (2004) https://doi.org/10.1016/j.cdp.2004.09.002
  3. Abdullaev, F. I. et al. In vitro evaluation of chemopreventive potential of saffron. Rev Invest Clin 54:430-436 (2002)
  4. Abdullaev, F. I. et al. Use of in vitro assays to assess the potential antigenotoxic and cytotoxic effects of saffron (Crocus sativus L.). Toxicol In Vitro 17:731-736 (2003) https://doi.org/10.1016/S0887-2333(03)00098-5
  5. Salomi, M. J., Nair, S. C. & Panikkar, K. R. Cytotoxicity and non-mutagenicity of Nigella sativa and saffron (Crocus sativus) in vitro. Proc Ker Sci Congr 5:244 (1991)
  6. Francis, F. J. Lesser-known food colorants. Food Technol 41(4):62-68 (1987)
  7. Francis, F. J. et al. Miscellaneous colorants. In Natural Food Colorants 7:242-272 (1992)
  8. Lin, J. K. & Wang, C. J. Protection of crocin dyes on the acute hepatic damage induced by aflatoxin B1 and dimethylnitrosamine in rats. Carcinogenesis 7:595-599 (1986) https://doi.org/10.1093/carcin/7.4.595
  9. Tseng, T. H., Chu, C. Y., Huang, J. M., Shiow, S. J. & Wang, C. J. Crocetin protects against oxidative damage in rat primary hepatocytes. Cancer Lett 97:61-67 (1995) https://doi.org/10.1016/0304-3835(95)03964-X
  10. Nair, S. C., Pannikar, B. & Panikkar, K. R. Antitumour activity of saffron (Crocus sativus). Cancer Lett 57:109-114 (1991) https://doi.org/10.1016/0304-3835(91)90203-T
  11. Nair, S. C., Kurumboor, S. K. & Hasegawa, J. H. Saffron chemoprevention in biology and medicine: a review. Cancer Biother 10:257-264 (1995) https://doi.org/10.1089/cbr.1995.10.257
  12. Nair, S. C., Varghese, C. D., Pannikar, K. R., Kurumboor, S. K. & Parathod, R. K. Effects of saffron on vitamin A levels and its antitumor activityonthegrowth of solid tumors in mice. Int J Pharmacog 32:105-114 (1994) https://doi.org/10.3109/13880209409082981
  13. Maron, D. M. & Ames, B. N. Revised methods for the Salmonella mutagenicity test. Mutation Res 113:173-215 (1983) https://doi.org/10.1016/0165-1161(83)90010-9
  14. Arimoto-Kobayashi, S., Machida, M., Okamoto, K. & Yamaguchi, A. Evaluation of photo-mutagenicity and photo-cytotoxicity of food coloring agents. Mutagenesis 20(3):229-233 (2005) https://doi.org/10.1093/mutage/gei030
  15. Ishidate, M. Data Book of Chromosomal Aberration Test in Vitro. Life-Science Information Center Press, Tokyo (1987)
  16. Ozaki, A. et al. Genotoxicity of gardenia yellow and its components. Food Chem Toxicol 40(11):1603-1610 (2002) https://doi.org/10.1016/S0278-6915(02)00118-7
  17. Akao, T., Kobayashi, K. & Aburada, M. Enzymic studies on the animal and intestinal bacterial metabolism of geniposide. Biol Pharmaceut Bull 17(12):1573-1576 (1994) https://doi.org/10.1248/bpb.17.1573
  18. Bors, W., Saran, M. & Michel, C. Radical intermediates involved in the bleaching of the carotenoid crocin. Hydroxyl radicals, superoxide anions and hydrated electrons. Int J Radiat Biol Relat Stud Phys Chem Med 41:493-501 (1982) https://doi.org/10.1080/09553008214550571
  19. Abdullaev, F. I. Biological effects of saffron. Biofactors 4(2):83-86 (1993)
  20. Pham, T. Q., Cormier, F., Farnworth, E., Tong, V. H. & Van Calsteren, M. R. Antioxidant properties of crocin from Gardenia jasminoides Ellis and study of the reactions of crocin with linoleic acid and crocin with oxygen. J Agric Food Chem 48:1455-1461 (2000) https://doi.org/10.1021/jf991263j
  21. Assimopoulou, A. N., Sinakos, Z. & Papageorgiou, V. P. Radical scavenging activity of Crocus sativus L. extract and its bioactive constituents. Phytother Res 19:997-1000 (2005) https://doi.org/10.1002/ptr.1749
  22. Khan, N., Afaq, F. & Mukhtar, H. Cancer chemoprevention through dietary antioxidants: progress and promise. Antioxid Redox Signal 10:475-510 (2008) https://doi.org/10.1089/ars.2007.1740
  23. Papandreou, M. A. et al. Inhibitory activity on amyloid-beta aggregation and antioxidant properties of Crocus sativus stigmas extract and its crocin constituents. J Agric Food Chem 54:8762-8768 (2006) https://doi.org/10.1021/jf061932a
  24. Hosseinzadeh, H. & Sadeghnia, H. R. Safranal, a constituent of Crocus sativus (saffron), attenuated cerebral ischemia induced oxidative damage in rat hippocampus. J Pharm Pharm Sci 8:394-399 (2005)
  25. Hosseinzadeh, H., Sadeghnia, H. R., Ziaee, T. & Danaee, A. Protective effect of aqueous saffron extract (Crocus sativus L.) and crocin, its active constituent, on renal ischemiareperfusion-induced oxidative damage in rats. J Pharm Pharm Sci 8:387-393 (2005)
  26. Saleem, S. et al. Effect of saffron (Crocus sativus) on neurobehavioral and neurochemical changes in cerebral ischemia in rats. J Med Food 9:246-253 (2006) https://doi.org/10.1089/jmf.2006.9.246
  27. Hosseinzadeh, H., Modaghegh, M. H. & Saffari, Z. Crocus Sativus L. (saffron) extract and its active constituents (crocin and safranal) on ischemia-reperfusion in rat skeletal muscle. eCAM (in press) (2008)
  28. Zheng, Y. Q., Liu, J. X., Wang, J. N. & Xu, L. Effects of crocin on reperfusion-induced oxidative nitrative injury to cerebral microvessels after global cerebral ischemia. Brain Res 1138:86-94 (2007) https://doi.org/10.1016/j.brainres.2006.12.064
  29. Ames, B. N., Durston, W. E., Yamasaki, E. & Lee, F. D. Carcinogens are mutagens: a simple test system combining liver homogenates for activation and bacteria for detection. Proc Natl Acad Sci USA 70:2281-2285 (1973)
  30. JEMS.MMS The atlas of chromosomal aberrations induced by chemicals. Asakura-Shoten, Tokyo (1988)
  31. Altman, D. G. Practical statistics for medical research. Comparing groups-categorical data, London, Chapman & Hall. 10:229-276 (1991)
  32. Clements, J. Gene mutation assays in mammalian cells. Methods in Molecular Biology 43:277-286 (1995)
  33. Singh, N. P., McCoy, M. T., Tice, R. R. & Schneider, E. L. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175:184-191 (1988) https://doi.org/10.1016/0014-4827(88)90265-0
  34. Singh, N. P., Stephens, R. E. & Schneider, E. L. Modifications of alkaline microgel electrophoresis for sensitive detection of DNA damage. Int J Radiat Biol 66:23-28 (1994) https://doi.org/10.1080/09553009414550911
  35. Ryu, J. C., Kim, H. J., Seo, Y. R. & Kim, K. R. Single Cell Gel Electrophoresis (Comet Assay) to detect DNA damage and Apoptosis in cell level. Environ Mutagens & Carcinogens 17(2):71-77 (1997)
  36. Tice, R. R. et al. Single cell gel/comet assay: guidelines for in vitro and in vivo genetic toxicology testing. Environ Mol Mutagen 35:206-221 (2000) https://doi.org/10.1002/(SICI)1098-2280(2000)35:3<206::AID-EM8>3.0.CO;2-J