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Makale Tam Makale Uluslararası 2003

Evidence for the involvement of human liver microsomes CYP1A2 in the mono-hydroxylation of daidzein

WX Peng, LS Wang, HD Li, Abdelaty Mostafa Abdelaty Hassıbelnaby, GL Chen, HH Zhou

Clinica chimica acta; international journal of clinical chemistry Cilt 334 · Sayı 1-2 · ss. 77–85 · 01.01.2003
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Özet

Background: In vitro studies with rats and human liver microsomes (HLM) demonstrated that daidzein is readily metabolized to niono-hydroxylated compounds. In this study, daidzem mono-hydroxylated metabolites was investigated using human liver microsomes to identify the cytochrome P450 (CYP) isoform(s) involved in this metabolic pathway. Methods: Kinetic analysis for the formation rates of mono-hydroxylated metabolites of daidzein, including 7,8,4'-trihydroxyisoflavone (7,8,4'-THI), 7,3,4'-trihydroxyisoflavone (7,3,4'-THI) and 6,7,4'-trihydroxyisoflavone (6,7,4'-THI), were performed using human liver microsomes (HLM) and recombinant enzymes at substrate concentrations ranging from 0.5 to 400 mumol/l. Nine selective inhibitors or substrate probes specific for different CYP isoforms were applied for screening the isoform(s) responsible for mono-hydroxylated metabolism of daidzein. Results: Michaelis-Menten kinetic parameters were best fitted to a one-component enzyme kinetic model. The mean K-m (mumol/l) and V-max, (mumol/g min) values (+/- S.D.) were 26.86 (10.45) and 4.76 (2.07), 53.83 (22.25) and 2.29 (1.04), 51.48 (29.32) and 2.21(0.82), for the formation rates of 7,8,4'-THI. 7.3',4-THI and 6,7,4'-THI, respectively. Furafylline, the CYP1A2-specific inhibitor, estrogen and monoclonal antibody raised against human CYP1A2 (MAB-1A2) substantially inhibited the formation rates of mono-hydroxylated metabolites. The IC50 of Fur for the formation of 7,3',4'-THI, 6,7,4'-THI and 7,8,4'-THI was 1.0, 0.9 and 0.8 mumol/l, respectively. The IC50 of estrogen for the formation of 7,3,4'-THI, 6,7,4-THI and 7,8,4'-THI was 51, 60 and 64 mumol/l. respectively. The IC50 of MAB-1A2 for the formation of the mono-hydroxylated products was 1 mumol/l, but neither other selective inhibitor nor substrate probes, including coumarin (CYP2D6), sulphaphenzole (CYP2C9/10), omeprazole (CYP2C19), quinidine (CYP2D6), diethyldithiocarbamate (CYP2E1), troleandomycin (CYP3A4) and keteconazole (CYP3A4), did so with human liver microsomes. Conclusion: Daidzein mono-hydroxylated products are principally metabolized by CYP1A2 in human. (C) 2003 Elsevier Science B.V. All rights reserved.

Sürdürülebilir Kalkınma Amaçları

  • SKA 3: Sağlıklı Bireyler

Atıf için künye

Peng, W., Wang, L., Li, H., Hassıbelnaby, A. M. A., Chen, G., & Zhou, H. (2003). Evidence for the involvement of human liver microsomes CYP1A2 in the mono-hydroxylation of daidzein. Clinica chimica acta; international journal of clinical chemistry, 334(1-2), 77–85. https://doi.org/10.1016/s0009-8981%2803%2900194-3

BibTeX 
@article{peng2003-209778,
  author = {Peng, WX and Wang, LS and Li, HD and Hassıbelnaby, Abdelaty Mostafa Abdelaty and Chen, GL and Zhou, HH},
  title = {Evidence for the involvement of human liver microsomes CYP1A2 in the mono-hydroxylation of daidzein},
  journal = {Clinica chimica acta; international journal of clinical chemistry},
  year = {2003},
  volume = {334},
  number = {1-2},
  pages = {77--85},
  issn = {0009-8981},
  doi = {10.1016/s0009-8981(03)00194-3},
  url = {https://akademik.atauni.edu.tr/yayinlar/209778-evidence-for-the-involvement-of-human-liver-microsomes-cyp1a2-in-the-mono}
}