Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
권호 표지
DOI QR코드

DOI QR Code

Investigation of the Regulatory Effects of Saccharin on Cytochrome P450s in Male ICR Mice

  • Jo, Jun Hyeon (BK21 Plus KNU Multi-Omics based Creative Drug Research Team, College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University) ;
  • Kim, Sunjoo (BK21 Plus KNU Multi-Omics based Creative Drug Research Team, College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University) ;
  • Jeon, Tae Won (Toxicological Research Center, Hoseo University) ;
  • Jeong, Tae Cheon (College of Pharmacy, Yeungmam University) ;
  • Lee, Sangkyu (BK21 Plus KNU Multi-Omics based Creative Drug Research Team, College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University)
  • Received : 2016.07.22
  • Accepted : 2016.08.30
  • Published : 2017.01.15
Download PDF
⟨ Previous Next ⟩

Abstract

Saccharin, the first artificial sweetener, was discovered in 1879 that do not have any calories and is approximately 200~700 times sweeter than sugar. Saccharin was the most common domestically produced sweetener in Korea in 2010, and it has been used as an alternative to sugar in many products. The interaction between artificial sweeteners and drugs may affect the drug metabolism in patients with diabetes, cancer, and liver damage, this interaction has not been clarified thus far. Here, we examined the effects of the potential saccharin-drug interaction on the activities of 5 cytochrome P450 (CYPs) in male ICR mice; further, we examined the effects of saccharin (4,000 mg/kg) on the pharmacokinetics of bupropion after pretreatment of mice with saccharin for 7 days and after concomitant administration of bupropion and saccharin. Our results showed saccharin did not have a significant effect on the 5 CYPs in the S9 fractions obtained from the liver of mice. In addition, we observed no differences in the pharmacokinetic parameters of bupropion between the control group and the groups pretreated with saccharin and that receiving concomitant administration of saccharin. Thus, our results showed that saccharin is safe and the risk of saccharin-drug interaction is very low.

Keywords

References

  1. Whitehouse, C.R., Boullata, J. and McCauley, L.A. (2008) The potential toxicity of artificial sweeteners. AAOHN J., 56, 251-259. https://doi.org/10.3928/08910162-20080601-02
  2. FDA Office of Public Affairs (2006) Artificial sweeteners: no calories...sweet! FDA Consum., 40, 27-28.
  3. Amin, K.A. and AlMuzafar, H.M. (2015) Alterations in lipid profile, oxidative stress and hepatic function in rat fed with saccharin and methyl-salicylates. Int. J. Clin. Exp. Med., 8, 6133-6144.
  4. Bailey, C.J., Day, C., Knapper, J.M., Turner, S.L. and Flatt, P.R. (1997) Antihyperglycaemic effect of saccharin in diabetic ob/ob mice. Br. J. Pharmacol., 120, 74-78. https://doi.org/10.1038/sj.bjp.0700871
  5. Qurrat-ul-Ain and Khan, S.A. (2015) Artificial sweeteners: safe or unsafe? J. Pak. Med. Assoc., 65, 225-227.
  6. Andreatta, M.M., Munoz, S.E., Lantieri, M.J., Eynard, A.R. and Navarro, A. (2008) Artificial sweetener consumption and urinary tract tumors in Cordoba, Argentina. Prev. Med., 47, 136-139. https://doi.org/10.1016/j.ypmed.2008.03.015
  7. Rendic, S. (2002) Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab. Rev., 34, 83-448. https://doi.org/10.1081/DMR-120001392
  8. Wang, H.B. and Tompkins, L.M. (2008) CYP2B6: New insights into a historically overlooked cytochrome P450 isozyme. Curr. Drug Metab., 9, 598-610. https://doi.org/10.2174/138920008785821710
  9. Mo, S.L., Liu, Y.H., Duan, W., Wei, M.Q., Kanwar, J.R. and Zhou, S.F. (2009) Substrate specificity, regulation, and polymorphism of human cytochrome P450 2B6. Curr. Drug Metab., 10, 730-753. https://doi.org/10.2174/138920009789895534
  10. Sim, J., Nam, W., Lee, D., Lee, S., O, H., Joo, J., Liu, K.H., Han, J.Y., Ki, S.H., Jeong, T.C., Lee, T. and Lee, S. (2015) Selective induction of hepatic cytochrome P450 2B activity by leelamine in vivo, as a potent novel inducer. Arch. Pharm. Res., 38, 725-733. https://doi.org/10.1007/s12272-014-0443-0
  11. Kawamoto, T., Sueyoshi, T., Zelko, I., Moore, R., Washburn, K. and Negishi, M. (1999) Phenobarbital-responsive nuclear translocation of the receptor CAR in induction of the CYP2B gene. Mol. Cell. Biol., 19, 6318-6322. https://doi.org/10.1128/MCB.19.9.6318
  12. Kamenickova, A., Pecova, M., Bachleda, P. and Dvorak, Z. (2013) Effects of artificial sweeteners on the AhR- and GRdependent CYP1A1 expression in primary human hepatocytes and human cancer cells. Toxicol. In Vitro, 27, 2283-2288. https://doi.org/10.1016/j.tiv.2013.10.001
  13. Ellman, G.L. (1959) Tissue sulfhydryl groups. Arch. Biochem. Biophys., 82, 70-77. https://doi.org/10.1016/0003-9861(59)90090-6
  14. Chung, M.S., Suh, H.J., Yoo, W., Choi, S.H., Cho, Y.J., Cho, Y.H. and Kim, C.J. (2005) Daily intake assessment of saccharin, stevioside, D-sorbitol and aspartame from various processed foods in Korea. Food Addit. Contam., 22, 1087-1097. https://doi.org/10.1080/02652030500202092
  15. Ha, M.S., Ha, S.D., Choi, S.H. and Bae, D.H. (2013) Assessment of Korean consumer exposure to sodium saccharin, aspartame and stevioside. Food Addit. Contam. Part A Chem. Anal. Control Expo. Risk Assess., 30, 1238-1247. https://doi.org/10.1080/19440049.2013.797114
  16. Huvaere, K., Vandevijvere, S., Hasni, M., Vinkx, C. and Van Loco, J. (2012) Dietary intake of artificial sweeteners by the Belgian population. Food Addit. Contam. Part A Chem. Anal. Control Expo. Risk Assess., 29, 54-65. https://doi.org/10.1080/19440049.2011.627572
  17. Bar, A. and Biermann, C. (1992) Intake of intense sweeteners in Germany. Z. Ernahrungswiss., 31, 25-39. https://doi.org/10.1007/BF01612550