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Modulation of xenobiotic conjugation enzymes by dihydromyricetin in rats

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Abstract

Dihydromyricetin, 3,3′,4′,5,5′,7-hexahydroxyflavanone, is a phytochemical occurring in high quantities in tree Hovenia dulcis. This flavanonol is effective in counteracting acute EtOH intoxication and in reducing excessive EtOH consumption. As dihydromyricetin is considered for a potential human use its interactions with biotransformation enzymes should be examined. In general, ingested foreign compounds (xenobiotics) might stimulate expression (induction) of these enzymes and/or inhibit their activities. Usually the metabolism of xenobiotics proceeds via two phases of sequential enzymatic conversion to facilitate their excretion from the body. As xenobiotics biotransformation enzymes of the phase II, sulfo- and N/O-acetyltransferases (SULTs and NATs), are involved in the process of carcinogen activation, their induction/inhibition by dihydromyricetin should be examined. Dihydromyricetin was administered to experimental rats by gastric gavages in three consecutive doses (60 mg/kg body weight/day). The induction of sulfo- and N/O-acetyltransferases was assessed based on the protein levels on Western blots and on their metabolic activity in cytosolic samples of liver, small intestines and colon. Moreover, dihydromyricetin the inhibition of sulfo- and N/O-acetyltransferase mediated activities was examined with recombinant enzymes. Dihydromyricetin induced SULT1A1 activity in all tissues were studied with the exception of small intestines but had no effect on N/O-acetyltransferases. While dihydromyricetin did not affect SULT1A1 specific activity, both NAT1 and NAT2 were effectively inhibited (IC50 <10 μmol dm−3).

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References

  1. Hyun T, Eom S, Yu C, Roitsch T (2010) Planta Med 76:943

    Article  CAS  Google Scholar 

  2. Youdim KA, Dobbie MS, Kuhnle G, Proteggente AR, Abbott NJ, Rice-Evans C (2003) J Neurochem 85:180

    Article  CAS  Google Scholar 

  3. Shen Y, Lindemeyer AK, Gonzalez C, Shao XM, Spigelman I, Olsen RW, Liang J (2012) J Neurosci 32:390

    Article  CAS  Google Scholar 

  4. Kim KH, Chung YT, Lee JH, Park YS, Shin MK, Kim HS, Kim DH, Lee HY (2000) Korean J Med Crop Sci 8:225

    Google Scholar 

  5. Chen SH, Zhong GS, Li AL, Li SH, Wu LK (2006) Zhongguo Zhong Yao Za Zhi 31:1094

    Google Scholar 

  6. Hou X, Zhang J, Ahmad H, Zhang H, Xu Z, Wang T (2014) PLoS One 9:1

    Google Scholar 

  7. Wang Z, Sun X, Feng Y, Liu X, Zhou L, Sui H, Ji Q, Qiukai E, Chen J, Wu L, Li Q (2017) Anticancer Drugs 28:281

    Article  CAS  Google Scholar 

  8. Xie J, Liu J, Chen TM, Lan Q, Zhang QY, Liu B, Dai D, Zhang WD, Hu LP, Zhu RZ (2015) World J Gastroenterol 21:5473

    Article  CAS  Google Scholar 

  9. Yoshikawa M, Murakami T, Ueda T, Yoshizumi S, Ninomiya K, Murakami N, Matsuda H, Saito M, Fujii W (1997) Yakugaku Zasshi 117:108

    Article  CAS  Google Scholar 

  10. Hodek P (2012) Flavonoids. In: Anzenbacher P (ed) Metabolism of drugs and other xenobiotics. Wiley VCH, Weinheim, p 543

    Chapter  Google Scholar 

  11. Hodek P, Trefil P, Stiborova M (2002) Chem Biol Interact 139:1

    Article  CAS  Google Scholar 

  12. Evans WE, Relling MV (1999) Science 286:487

    Article  CAS  Google Scholar 

  13. Hodek P, Krizkova J, Burdova K, Sulc M, Kizek R, Hudecek J, Stiborova M (2009) Chem Biol Interact 180:1

    Article  CAS  Google Scholar 

  14. Hodek P, Fousova P, Brabencova E, Moserova M, Pavek P, Anzenbacherova E, Brotanek J, Hudecek J, Frei E, Stiborova M (2014) Neuro Endocrinol Lett 35:158

    CAS  Google Scholar 

  15. Bostikova Z, Moserova M, Pavek P, Stiborova M, Hodek P (2015) Neuro Endocrinol Lett 36:46

    Google Scholar 

  16. Coughtrie MWH (2016) Chem Biol Interact 259:2

    Article  CAS  Google Scholar 

  17. Riches Z, Stanley EL, Bloomer JC, Coughtrie MWH (2009) Drug Metab Dispos 37:2255

    Article  CAS  Google Scholar 

  18. Eaton EA, Walle UK, Lewis AJ (1996) Drug Metab Dispos 24:232

    CAS  Google Scholar 

  19. Maiti S, Chen X, Chen G (2005) Basic Clin Pharmacol Toxicol 96:44

    Article  CAS  Google Scholar 

  20. Chen Y, Huang C, Zhou T, Zhang S, Chen G (2010) J Mol Toxicol 24:102

    Article  Google Scholar 

  21. Zhou T, Chen Y, Chen G (2011) J Appl Toxicol 32:804

    Article  CAS  Google Scholar 

  22. Ishibe N, Sinha R, Hein DW, Kulldorff M, Strickland P, Fretland AJ, Chow WH, Kadlubar FF, Lang NP, Rothman N (2002) Pharmacogenetics 12:145

    Article  CAS  Google Scholar 

  23. Kukongviriyapan V, Phromsopha N, Tassaneeyakul W, Kukongviriyapan U, Sripa B, Hahnvajanawong V, Bhudhisawasdi V (2006) Xenobiotica 36:15

    Article  CAS  Google Scholar 

  24. Zhang Q, Liu J, Liu B, Xia J, Chen N, Chen X, Cao Y, Zhang C, Lu C, Li M, Zhu R (2014) Sci Rep 4:4628

    Article  Google Scholar 

  25. Krizkova J, Burdova K, Hudecek J, Stiborova M, Hodek P (2008) Neuroendocrinol Lett 29:717

    CAS  Google Scholar 

  26. Hodek P, Krizkova J, Frei E, Singgh R, Artl VM, Stiborova M (2011) Neuroendocrinol Lett 32:25

    CAS  Google Scholar 

  27. Weichelman KJ, Braun RD, Fitzpatrick JD (1988) Anal Biochem 175:231

    Article  Google Scholar 

  28. Frame LT, Ozawa S, Nowell SA, Chou H-C, Delongchamp RR, Doerge DR, Lang NP, Kadlubar FF (2000) Drug Metab Dispos 28:1063

    CAS  Google Scholar 

  29. Mulder GJ, Hinson JA, Gillette JR (1977) Biochem Pharmacol 26:189

    Article  CAS  Google Scholar 

  30. Brooke EW, Davies SG, Mulvaney AW, Pompeo F, Sim E, Vickers RJ (2003) Bioorg Med Chem 11:1227

    Article  CAS  Google Scholar 

  31. Riddles PW, Blakeley RL, Zerner B (1983) Methods Enzymol 91:49

    Article  CAS  Google Scholar 

  32. Laemmli UK (1970) Nature 227:680

    Article  CAS  Google Scholar 

  33. Nagar S, Walther S, Blanchard RL (2006) Mol Pharmacol 69:2084

    Article  CAS  Google Scholar 

  34. Walle T, Eaton EA, Walle UK (1995) Biochem Pharmacol 50:731

    Article  CAS  Google Scholar 

  35. James MO, Ambadapadi S (2013) Drug Metab Rev 45:401

    Article  CAS  Google Scholar 

  36. Ghazali RA, Waring RH (1999) Life Sci 65:1625

    Article  CAS  Google Scholar 

  37. De Santi C, Pietrabissa A, Mosca F, Rane A, Pacifici GM (2008) Xenobiotica 32:363

    Article  Google Scholar 

  38. Nishimuta H, Ohtani H, Tsujimoto M, Ogura K, Hiratskuka A, Sawada Y (2007) Biopharm Drug Dispos 28:491

    Article  CAS  Google Scholar 

  39. Venkatakrishnan K, Von Moltke LL, Greenblatt DJ (2001) J Clin Pharmacol 41:1149

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Supported by Grant P303/12/G163 from the Grant Agency of the Czech Republic.

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Science, Charles University, Hlavova 8, 128 40, Prague 2, Czech Republic

    Michaela Bebová, Zdislava Boštíková, Michaela Moserová, Marie Stiborová & Petr Hodek

  2. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Charles University, Heyrovského 1203, 500 05, Hradec Králové, Czech Republic

    Petr Pávek

  3. Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacky University, Hněvotínská 3, 775 15, Olomouc, Czech Republic

    Eva Anzenbacherová

Authors
  1. Michaela Bebová
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  2. Zdislava Boštíková
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  3. Michaela Moserová
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  4. Petr Pávek
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  5. Eva Anzenbacherová
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  6. Marie Stiborová
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  7. Petr Hodek
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Correspondence to Petr Hodek.

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Bebová, M., Boštíková, Z., Moserová, M. et al. Modulation of xenobiotic conjugation enzymes by dihydromyricetin in rats. Monatsh Chem 148, 2003–2009 (2017). https://doi.org/10.1007/s00706-017-2007-8

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  • DOI: https://doi.org/10.1007/s00706-017-2007-8

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