Evaluation of the mutagenic and genotoxic potential of ubiquinol

International Journal of Toxicology

Volumn 26, Issue 6, 2007, Pages 533-544

  Kitano, Mitsuaki ^a   Mizuhashi, Fukutaro ^b   Kubo, Hiroshi ^a   Kishida, Hideyuki ^a   Fujii, Kenji ^a   Kitahara, Mikio ^a   Hosoe, Kazunori ^a  

^a KANEKA CORPORATION   (Japan)

^b Biosafety Research Center   (Japan)

Author keywords

Clastogenicity; Coenzyme Q10; Genotoxicity; Mutagenicity; Ubiquinol; Ubiquinone

Indexed keywords

UBIQUINONE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BACTERIAL STRAIN; BONE MARROW; CHROMOSOME ABERRATION; CONTROLLED STUDY; ESCHERICHIA COLI; GENOTOXICITY; GOOD LABORATORY PRACTICE; IN VIVO STUDY; LUNG FIBROBLAST; MALE; METABOLIC ACTIVATION; MICRONUCLEUS TEST; MUTAGENICITY; NONHUMAN; RAT; REVERTANT; SALMONELLA TYPHIMURIUM;

ANIMALS; ANTIOXIDANTS; CELLS, CULTURED; CHROMOSOME ABERRATIONS; CRICETINAE; CRICETULUS; ESCHERICHIA COLI; MALE; MUTAGENICITY TESTS; RATS; RATS, SPRAGUE-DAWLEY; SALMONELLA TYPHIMURIUM; UBIQUINONE;

BACTERIA (MICROORGANISMS); CRICETULUS GRISEUS; ESCHERICHIA COLI; RATTUS; SALMONELLA TYPHIMURIUM;

EID: 36849005066     PISSN: 10915818     EISSN: 1092874X     Source Type: Journal    
DOI: 10.1080/10915810701707460     Document Type: Article

References (70)

1. Aberg, F., E. L. Appelkvist, G. Dallner, and L. Ernster. 1992. Distribution and redox state of ubiquinones in rat and human tissues. Arch. Biochem. Biophys. 295:230-234
2. Ames, B. N., W. E. Durston, E. Yamasaki, and F. D. Lee. 1973. Carcinogens are mutagens: a simple test system combining liver homogenates for activation and bacteria for detection. Proc. Nat. Acad. Sci. U.S.A. 70:2281-2285.
3. Ames, B. N., F. D. Lee, and W. E. Durston. 1973. An improved bacterial test system for the detection and classification of mutagens and carcinogens. Proc. Nat. Acad. Sci. U.S.A. 70:782-786.
4. Ames, B. N., J. McCann, and E. Yamasaki. 1975. Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test. Mutat. Res. 31:347-364.
5. Arroyo, A., V. E. Kagan, V. A. Tyurin, J. R. Burgess, R. de Cabo, and P. Navas. 2000. NADH and NADPH-dependent reduction of coenzyme Q at the plasma membrane. Antioxidants Redox Signal. 2:251-262.
6. Battino, M., E. Ferri, A. Gorini, R. F. Villa, J. F. R. Huertas, P. Fiorella, M. L. Genova, G. Lenaz, and M. Marchetti. 1992. Natural distribution and occurrence of coenzyme Q homologues. Membr. Biochem. 9:179-190.
7. Bertelli, A., and G. Ronca. 1990. Carnitine and coenzyme Q10: biochemical properties and functions, synergism and complementary action. Int. J. Tissue React. 12:183-186.
8. Budavari, S., M. J. O'Neil, A. Smith, P. E. Heckelman, and J. F. Kinneary, eds. 1996. The Merck Index. An encyclopedia of chemicals, drugs and biologicals, 12th ed., 9978. Rahway, NJ: Merck & Co..
9. Chiba, T., T. Watanabe, Y. Kume, K. Sugiyama, and H. Shiojiri. 1972a. Toxicological studies of ubiquinone-10. (I). Acute toxicity tests in rats and mice and subacute and chronic toxicity tests in rats. Oyo Yakuri 6:769-779.
10. Chiba, T., K. Sugiyama, Y. Kume, H. Shiojiri, T. Watanabe, and M. Ozeki. 1972b. Toxicological studies of ubiquinone-10. (II). Subacute toxicity tests in rabbits. Oyo Yakuri 6:781-786.
11. Crane, F. L. 2001. Biochemical functions of coenzyme Q10. J. Am. Coll. Nutr. 20: 591-598.
12. Crane, F. L., I. L. Sun, and E. E. Sun. 1993. The essential functions of coenzyme Q. Clin. Investig. 71:S55-S59.
13. Dunnett, C. W. 1964. New tables for multiple comparisons with a control. Biometrics 20:482-491.
14. 10, α-tocopherol and cholesterol in biological samples by coupled-column liquid chromatography with coulometric and ultraviolet detection. J. Chromatogr. 425:87.
15. Ernster, L., and G. Dallner. 1995. Biochemical, physiological and medical aspects of ubiquinone function. Biochim. Biophys. Acta 1271:195-204.
16. Ernster, L., and P. Forsmark-Andree. 1993. Ubiquinol: An endogenous antioxidant in aerobic organisms. Clin. Invest. 71:S60.
17. Evance, H. J. 1976. Cytological methods of detecting chemical mutagens. In Chemical mutagens, vol. 4, ed. A. Hollaender, 1-25. New York: Plenum Press.
18. FDA. 2000. Principles for the safety assessment of food ingredients. Food and Drug Administration, Redbook 2000.
19. Forsmark-Andree, P., C. P. Lee, G. Dallner, and L. Ernster. 1997. Lipid peroxidation and changes in the ubiquinone content and the respiratory chain enzymes of submitochondrial particles. Free Radic. Biol. Med. 22:391-400. Cited in Ibrahim et al. 2000.
20. Frei B., M. C. Kim, and B. N. Ames. 1990. Ubiquinol-10 is an effective lipid-soluble antioxidant at physiological concentrations. Proc. Natl. Acad. Sci. U.S.A. 87:4879-4883.
21. Greenberg, S., and W. H. Frishman. 1990. Co-enzyme Q10: A new drug for cardiovascular disease. J. Clin. Pharmacol. 30: 596-608.
22. Hayashi, M., T. Sofuni, and M. Ishidate Jr. 1984. A pilot experiment for the micronucleus test - The multi-sampling at multi-dose levels method. Mutat. Res. 141:165-169.
23. Hendler, S. S., and M. S. Rorvik, eds. 2001. PDR for Nutritional Supplements, 103-106. Montvale, NJ: Medical Economics.
24. Hosoe, K., M. Kitano, H. Kishida, H. Kubo, K. Fujii, and M. Kitahara. 2007. Study on safety and bioavailability of ubiquinol (Kaneka QHTM) after single and 4-week multiple oral administration to healthy volunteers. Regul. Toxicol. Pharmacol. 47:19-28.
25. Hughes, K., B. L. Lee, X. Feng, J. Lee, and C. N. Ong. 2002. Coenzyme Q10 and differences in coronary heart disease risk in Asian Indians and Chinese. Free Radic. Biol. Med. 32:132-138.
26. Ibrahim, W. H., H. N. Bhagavan, R. K. Chopra, and C. K. Chow. 2000. Dietary coenzyme Q10 and vitamin E alter the status of these compounds in rat tissues and mitochondria. J. Nutr. 130:2343-2348.
27. ICH Harmonized Tripartite Guildeline. Guidance on specific aspects of regulatory genotoxicty tests for pharmaceuticals. Recommended for adoption at Step 4 of the ICH process on 19 July 1995.
28. Ishidate, M. 1979. Chromosome aberration test in vitro for chemical mutagens in our environment. Tissue Culture 5:115-122.
29. Ishidate, M. 1987. Chromosomal aberration test in vitro. Tokyo: REALIZE INC.
30. Ishidate, M. Jr., ed. 1991. [The data book for mutagenicity assay using microorganisms.] [Article in Japanese.] Life-science Information Center Press.
31. Ishidate, M. Jr., and S. Odashima. 1977. Chromosome tests with 134 compounds on Chinese hamster cells in vitro - Ascreening method for chemical carcinogens. Mutat. Res. 48:337-354.
32. Jones, K., K., Hughes, L., Mischley, and D. J. McKenna. 2002. Coenzyme Q10: Efficacy, safety, and use. Alternat. Ther. 8:42-55.
33. Kastenbaum, M. A., and K. O. Bowman. 1970. Tables for determining the statistical significance of mutation frequencies. Mutat. Res. 9:527-549.
34. Kawaguchi, Y., H. Hayashi, M. Sato, and Y. Shindo. 1997. Needle crystals of vitamin B2 induce polyploidy in Chinese hamster lung (CHL/IU) cells. Mutat. Res. 373:1-7.
35. Kawataba, M., H. Takasawa, S. Minowa, M. Nakajima, and S. Hamada. 2007. New method of specimen preparation for a micronucleus test. Genes Environ 29:100-106.
36. Kirkland, D. 1994. Report of in vitro sub-group. International Workshop on Standardisation of Genotoxicity Test Procedures. Mutat. Res. 312:211-215.
37. Kitano, M., K. Hosoe, N. Fukutomi, T. Hidaka, R. Ohta, K. Yamakage, and T. Hara. 2006. Evaluation of the mutagenic potential of ubidecarenone using three short-term assays. Food Chem. Toxicol. 44:364-370.
38. Kitano, M., S. Oda, D. Watanabe, H. Kubo, H. Kishida, K. Fujii, M. Kitahara, and K. Hosoe. Comparison of the subchronic oral toxicity of ubiquinol in rats and dogs. Submitted.
39. Kubo, H., K. Fujii, T. Kawabe, S. Matsumoto, H. Kishida, and K. Hosoe. Food content of Ubiquinol-10, a reduced form of Coenzyme Q10. Submitted.
40. Lass, A., and R. S. Sohal. 1999. Comparisons of coenzyme Q bound to mitochondrial membrane proteins among different mammalian species. Free Radic Biol Med. 27:220-226.
41. Lenaz, G. 2001. A critical appraisal of the mitochondrial coenzyme Q pool. FEBS Lett. 509:151-155.
42. Mae, T., Y. Sakamoto, S. Morikawa, and T. Hidaka. 2001. Pharmaceutical composition comprising coenzyme Q10. US patent no. 6,184,255 B1.
43. Maron, D., J. Katzenellenbogen, and B. N. Ames. 1981. Compatibility of organic solvents with the Salmonella/microsome test. Mutat. Res. 88: 343-350.
44. Matsuoka, A., M. Hayashi, and M. Ishidate Jr. 1979. Chromosomal aberration tests on 29 chemicals combined with S9 mix in vitro. Mutat. Res. 66:277-290.
45. Matthews, R. T., L. Yang, S. Browne, M. Baik, and M. F. Beal. 1998. Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects. Proc. Natl. Acad. Sci. U.S.A. 95:8892-8897.
46. Ministry of Labor, Industrial Safety and Health Department. 1991. [Test Guidelines and GLP for Mutagenicity Test using Microorganisms in the Safety and Health Law.] [In Japanese.] Tokyo: Japan Industrial Safety and Heath Association.
47. Noack, H., U. Kube, and W. Augustin. 1994. Relations between tocopherol depletion and coenzyme Q during lipid peroxidation in rat liver mitochondria. Free Radic. Res. 20:375-386. Cited in Ibrahim et al. 2000.
48. Nohl, H., L. Gille, and K. Staniek. 1998. The biochemical, pathophysiological, and medical aspects of ubiquinone function. Ann. N. Y. Acad. Sci. 854:394-409.
49. Nohl, H., A. V. Kozlov, K. Staniek, and L. Gille. 2001. The multiple functions of coenzyme Q. Bioorg. Chem. 29:1-13.
50. Notake, Y., S. Tamura, S. Toyoshima, H. Fujita, Y. Suzuki, and T. Chiba. 1972. Effects of coenzyme Q10 on development of the fetuses and neonates in rats and mice. Iyakuhin Kenkyu 3:306-315.
51. OECD Guidelines for the Testing of Chemicals. Test No. 471: Bacterial Reverse Mutation Test. Paris: Organisation for Economic Co-operation and Development.
52. OECD Guidelines for the Testing of Chemicals. Test No. 473: In vitro Mammalian Chromosome Aberration Test. Paris: Organisation for Economic Co-operation and Development.
53. OECD Guidelines for the Testing of Chemicals. Test No. 474: Mammalian Erythrocyte Micronucleus Test. Paris: Organisation for Economic Co-operation and Development.
54. Okamoto, T., T. Matsuya, Y. Fukunaga, T. Kishi, and T. Yamagami. 1989. Human serum ubiquinol-10 levels and relationship to serum lipids. Int. J. Vit. Nutr. Res. 59:288.
55. Overvad, K., B. Diamant, L. Holm, G. Hølmer, S. A. Mortensen, and S. Stender. 1999. Review of coenzyme Q10 in health and disease. Eur. J. Clin. Nutr. 53:764-770.
56. Pepping, J. 1999. Coenzyme Q10. Am. J. Health Syst. Pharm. 56:519-521.
57. Ramasarma, T. 1985. Natural occurrence and distribution of coenzyme Q. In Coenzyme Q: Biochemical, bioenergetics and clinical applications of ubiquinone, ed. G. Lenaz, 67-81. New York: John Wiley & Sons.
58. Report of the Ad Hoc Committee of the Environmental Mutagen Society and the Institute for Medical Research [editorial]. 1972. Toxicol. Appl. Pharamcol. 22:269-275.
59. Salamone, M., and J. Heddle. 1980. The micronucleus assay: Testing with an improved protocol. Environ. Mutagen. 3:303.
60. Schmid, W. 1975. The micronucleus test. Mutat. Res. 31:9-15.
61. Schmid, W. 1976. The micronucleus test for cytogenic analysis. Chemical mutagens, Vol 4, ed. A. Hollaender, 31-53. New York: Plenum Press.
62. Schoepp, G. 1997. Is coenzyme Q10 (ubiquinone) effective for the treatment of heart failure? Pharmacy Practice (Canada) 13:31-32.
63. Schultz, J. R., L. M. Ellerby, E. B. Gralla, J. S. Valentine, and C. F. Clarke. 1996. Autoxidation of ubiquinol-6 is independent of superoxide dismutase. Biochemistry 35:6595.
64. Stocker, R. and B. Frei. 1991. Endogenous antioxidant defenses in human blood plasma. In Oxidative stress: Oxidants and antioxidants, ed. H. Sies, 213-243. San Diego: Academic Press.
65. Stocker, R. and C. Suarna. 1993. Extracellular reduction of ubiquinone-1 and -10 by human Hep G2 and blood cells. Biochem. Biophys. Acta 1158:15-22.
66. Takahashi, T., T. Okamoto, K. Mori, H. Sayo, and T. Kishi. 1993. Distribution of ubiquinone and ubiquinol homologues in rat tissues and subcellular fractions. Lipids 28:803-809.
67. Tran, M. T., T. M., Mitchell, D. T., Kennedy, and J. T. Giles. 2001. Role of coenzyme Q10 in chronic heart failure, angina, and hypertension. Pharmacotherapy 21:797-806.
68. Williams, K. D., J. D. Maneke, M. AbdelHameed, R. L. Hall, T. E. Palmer, M. Kitano, and T. Hidaka. 1999. 52-Week oral gavage chronic toxicity study with ubiquinone in rats with a 4-week recovery. J. Agric. Food Chem. 47:3756-3763.
69. Yahagi, T. 1975. [Screening methods using microbes for the environmental carcinogens (author's transl).] [Article in Japanese.] Protein, Nucleic Acid and Enzyme 20:16-27.
70. Yamashita, S., and Y. Yamamoto. 1997. Simultaneous detection of ubiquinol and ubiquinone in human plasma as a marker of oxidative stress. Anal. Biochem. 250:66-73.