Archives of Pharmacal Research

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Effects of Hydroxylated Flavonoids on the Ethoxyresorufin O-deethylase and Benzo($\alpha$)pyrene Hydroxylase

  • Published : 1996.12.01
Download PDF
⟨ Previous Next ⟩

Abstract

In order to understand the mechanism of action of flavonoids on the drug metabolizing enzyme, cytochrome P450IA1, this study was undertaken to examine the effect of chrysin, morin, myricetin and aminopyrine on the activities of ethoxyresorufin O-deethylase and benzo(.alpha.) pyrene hydroxylase in the liver. In the isolated perfused rat liver that was pretreated with 3-methylcholanthrene (3MC), chrysin, morin, myricetin and aminopyrine inhibited the activity of ethoxyresorufin O-deethylase with concentration dependent manner. The isolated liver perfusion with chrysin, morin, myricetin and aminopyrine showed inhibition on the induction of ethoxyresorufin O- deethylase by 3MC. And also, in mouse liver hepa I cells, 3MC-stimulated the benzo(.alpha.)pyrene hydroxylase activity which was inhibited by chrysin, morin, myricetin and aminopyrine. These results strongly suggested that hydoxylated flavonoids interfered not only the induction of cytochrome P45OIA1 enzymes by 3MC but also the interaction of substrates and enzyme.

Keywords

References

  1. Cancer Research v.41 Activation and inhibition of benzo(α)pyrene and aflatoxin $B_1$ metabolism in human liver microsomes by naturally occuring flavonoids Buening,M.K.;Chang,R.L.;Huang,Mou-Tuan;Forther,J.G;Wood,A.W.;Conney,A.H.
  2. Toxicol. Appl. Pharmacol. v.136 Differential effects of nonhydroxylated flavonoids as inducers of cytochrome P450 IA and IIB isozymes in rat liver Canivenc-Lavier,M.C.;Bentejac,M.;Miller,M.L.;Leclerc,J.;Siess,M.H.;Latruffe,N.;Suschetet,M.
  3. Plants Flavonoids in biology and medicine II : Biochemical celluar and Medicinal Properties Cody,V.;Middleform,E.;Itaborne,J.B.;Beretz,A.
  4. Flavonoids in Biology and Medicine III : structure and activity Das,N.P.
  5. J. Biol. Chem. v.85 The DNA recognition site for the dioxin-Ah receptor complex Denison,M.S.;Fisher,J.M.;Whitlock,J.P.
  6. Flavonoids and Bioflavonoids : physiology and pharmacology Farkas,L.;Garbor,M.;Kally,F.
  7. Archives of Biochemistry and Biophysics v.239 3-Methyl-cholanthrene-induced expression of the cytochrome P-450c gene Foldes,R.L.;Hines,R.N.;Ho,Kai-Ling;Shen,Mei-Ling;Nagel,K.B.;Bresnic,E.
  8. J. Biol. Chem. v.259 Monoclonal antibody-directed phenotyping of cytochrome P-450 dependent aryl hydrocarbon hydroxylase and 7-ethoxycoumarin deethylase in mammalian tissues Fujino,T.;West,D.;Park,S.S.;Gelboin,H.V.
  9. Cancer Research v.48 Roles of cytochrome P-450 enzymes in chemical carcinogenesis and cancer chemotherapy Guengerich,F.P
  10. Proc. Natl. Acad. Sci. v.86 Specific protein-DNA interaction at a xenobiotic-responsive element: Copurification of dioxin receptor and DNA-binding activity Hapgood,J.;Cuthill,S.;Denis,M.;Poellinger,L.;Gustafsson,J.A.
  11. Carcinogenesis v.9 Identification of multiple regulatory elements on the human cytochrome P450IA1 gene Hines,R.N.;Mathis,J.M.;Jacob,C.S.
  12. J. Biol. Chem. v.255 Temperature-dependent cytosol-to-nucleus translocation of the Ah receptor for 2,3,7,8-tetra-chlorodibenzo-p-dioxin in continuous cell culture lines Okey,A.B.;Bondy,G.P.;Mason,M.E.;Nebert,D.W.;Forster-Gibson,C.J.;Muncan,J.;Dufresne,M.J.
  13. Plants Flavonoids in biology and medicine: Biochemical, pharmacological and structure-activity relationships Selway,J.W.T.;Cody,V.(ed.);Middleton,E.(ed.);Harbone,J.B.(ed.)
  14. Arch. Biochem. Biophys. v.240 Inhibition of cytochrome P-450 activity in rat liver microsomes by the naturally occuring flavonoid, quercetin Sousa,R.L.;Marletta,M.A.
  15. Biochem. Pharmacol. v.48 Pretranslational induction of cytochrome P450IA enzymes by β-Naphthoflavone and 3-Methyl-cholanthrene occurs in different liver zones Teija,O.;Sirkku,S.;Kirsti H.;Ari,H.;Kai,O.L.
  16. Endeavour v.10 Flanonoids and food Tinberlake,C.F.;Henry,B.S.
  17. Ann. Rev. Pharmacol. Toxicol. v.26 The regulation of cytochrome P-450 gene expression Whitlock,J.P.Jr.
  18. Biochemistry v.31 DNA sequence determinants for binding of transformed Ah receptor to a dioxin-responsive enhancer Yao,E.F.;Denison,M.S.