Role of Metabolism by Intestinal Bacteria in Arbutin-Induced Suppression of Lymphoproliferative Response in vitro

  • Received : 2011.11.30
  • Accepted : 2011.12.20
  • Published : 2012.03.31


Role of metabolism by intestinal bacteria in arbutin-induced immunotoxicity was investigated in splenocyte cultures. Following an incubation of arbutin with 5 different intestinal bacteria for 24 hr, its aglycone hydroquinone could be produced and detected in the bacterial culture media with different amounts. Toxic effects of activated arbutin by intestinal bacteria on lymphoproliferative response were tested in splenocyte cultures from normal mice. Lipopolysaccharide and concanavalin A were used as mitogens for B- and T-cells, respectively. When bacteria cultured medium with arbutin was treated into the splenocytes for 3 days, the medium cultured with bacteria producing large amounts of hydroquinone induced suppression of lymphoproliferative responses, indicating that metabolic activation by intestinal bacteria might be required in arbutin-induced toxicity. The results indicated that the present testing system might be applied for determining the possible role of metabolism by intestinal bacteria in certain chemical-induced immunotoxicity in animal cell cultures.


Supported by : Yeungnam University


  1. Blaut, M., Braune, A., Wunderlich, S., Sauer, P., Schneider, H. and Glatt, H. (2006) Mutagenicity of arbutin in mammalian cells after activation by human intestinal bacteria. Food. Chem. Toxicol. 44, 1940-1947.
  2. Deisinger, P. J., Hill, T. S. and English, J. C. (1996) Human exposure to naturally occurring hydroquinone. J. Toxicol. Environ. Health. 47, 31-46.
  3. Gorbach, S. L., Nahas, L., Lerner, P. I. and Weinstein, L. (1967) Studies of intestinal microfl ora. I. Effects of diet, age, and periodic sampling on numbers of fecal microorganisms in man. Gastroenterology. 53, 845-855.
  4. Jin, M. J., Kim, U., Kim, I. S., Kim, Y., Kim, D. H., Han, S. B., Kim, D. H., Kwon, O. S. and Yoo, H. H. (2010) Effects of gut microfl ora on pharmacokinetics of hesperidin: a study on non-antibiotic and pseudogerm- free rats. J. Toxicol. Environ. Health. A. 73, 1441-1450.
  5. Kang, M. J., Ha, H. W., Kim, H. G., Lee, D. H., Kong, M. J., Ahn, Y. T., Kim, D. H., Shin, B. S., Kang, W., Jeong, H. G. and Jeong, T. C. (2011) Role of metabolism by intestinal bacteria in arbutin-induced toxicity in vitro. Arch. Pharm. Res. 34, 687-693.
  6. Khanal, T., Kim, H. G., Hwang, Y. P., Kong, M. J., Kang, M. J., Yeo, H. K., Kim, D. H., Jeong, T. C. and Jeong, H. G. (2011) Role of metabolism by the human intestinal microfl ora in arbutin-induced cytotoxicity in HepG2 cell cultures. Biochem. Biophys. Res. Commun. 413, 318-324.
  7. Lennernäs, H. and Abrahamsson, B. (2005) The use of biopharmaceutic classifi cation of drugs in drug discovery and development: current status and future extension. J. Pharm. Pharmacol. 57, 273- 285.
  8. Robertson, J. D. and Orrenius, S. (2000) Molecular mechanisms of apoptosis induced by cytotoxic chemicals. Crit. Rev. Toxicol. 30, 609-627.
  9. Rubio, V., Zhang, J., Valverde, M., Rojas, E. and Shi, Z. Z. (2011) Essential role of Nrf2 in protection against hydroquinone- and benzoquinone- induced cytotoxicity. Toxicol. In. Vitro. 25, 521-529.
  10. Shamat, M. A. (1993) The role of the gastrointestinal microfl ora in the metabolism of drugs. Int. J. Pharm. 97, 1-13.
  11. Sousa, T., Paterson, R., Moore, V., Carlsson, A., Abrahamsson, B. and Basit, A. W. (2008) The gastrointestinal microbiota as a site for the biotransformation of drugs. Int. J. Pharm. 363, 1-25.
  12. Terasaka, H., Kadoma, Y., Sakagami, H. and Fujisawa, S. (2005) Cytotoxicity and apoptosis-inducing activity of bisphenol A and hydroquinone in HL-60 cells. Anticancer Res. 25, 2241-2247.
  13. Zhao-Yang, Z., Ke-Sen, X., Qing-Si, H., Wei-Bo, N., Jia-Yong, W., Yue-Tang, M., Jin-Shen, W., Guo-Qiang, W., Guang-Yun, Y. and Jun, N. (2008) Signaling and regulatory mechanisms of integrin alphavbeta6 on the apoptosis of colon cancer cells. Cancer Lett. 266, 209-115.

Cited by

  1. Role of intestinal microflora in xenobiotic-induced toxicity vol.57, pp.1, 2013,
  2. The effect of gut microbiota on drug metabolism vol.9, pp.10, 2013,
  3. Role of Intestinal Microbiota in Baicalin-Induced Drug Interaction and Its Pharmacokinetics vol.21, pp.3, 2016,
  4. L.) water leaf extract and arbutin pp.1525-6014, 2018,