Modulation of cytochrome P-450 dependent monooxygenases in streptozotocin-induced diabetic hamster: I. Effects of propofol on defluorination and cytochrome P-450 activities

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Abstract

Background: Diabetes mellitus could induce polymorphic alterations of metabolic activities of cytochrome P-450 dependent monooxygenases in chemical-induced diabetic animals. The purpose of this study is to define the functional impact of clinical concentrations of propofol on the metabolic activities of cytochrome P-450 in the diabetic animals. Methods: In order to validate the effect of propofol on cytochrome P-450 activities, especially the cytochrome P-450 2E1 and its defluorination activity, we applied NADPH-generating system to measure the metabolizing activities to cytochrome P-450 isozymes of streptozotocin-induced diabetic hamsters within the microsomes preincubated with various concentrations of propofol. The extent of defluorination and activity of cytochrome P-450 2E1 were assessed by reacting the propofol-treated microsomes in NADPH-generating system with enflurane and aniline as substrates respectively. Drug metabolizing activities of cytochrome 1A1, 2B1, and 3A4 were evaluated by metabolizing specific substrates, benzo(a)pyrene, pentoxyresorufin and erythromycin, within the microsomes of diabetic hamsters preincubated with various concentrations of propofol. Results: The hepatic and renal defluorination of influrane was significantly inhibited by 0.05 and 0.10 mM propofol in the microsomes of diabetic hamster (P <0.05). The activities of aniline hydroxylase (cytochrome 2E1), pentoxyresorufin O-dealkylase (cytochrome 2B1) and benzo(a)pyrene hydroxylase (cytochrome 1A1) were inhibited by propofol in a concentration-dependent manner from 0.05 to 0.10 mM. However, propofol showed no significant effect of the erythromycin N-demethylase (cytochrome 3A4) at its concentration of 0.05 - 0.10 mM in the diabetic hamsters. Conclusions: Our data demonstrated that propofol in therapeutic concentrations of 0.05 and 0.10 mM, could inhibit both liver and kidney defluorination and cytochrome P-450's activities of the diabetic hamsters in vitro of different extent. This should remind clinicians of propofol's potential drug-to-drug interactions in the diabetic patients.

Original languageEnglish
Pages (from-to)15-21
Number of pages7
JournalActa Anaesthesiologica Sinica
Volume38
Issue number1
Publication statusPublished - Mar 2000

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Propofol
Streptozocin
Cricetinae
Cytochrome P-450 Enzyme System
Cytochromes
Microsomes
NADP
Benzopyrene Hydroxylase
Aniline Hydroxylase
Cytochrome P-450 CYP2B1
Kidney
Cytochrome P-450 CYP3A
Enflurane
Benzo(a)pyrene
Liver
Erythromycin
Drug Interactions
Pharmaceutical Preparations
Isoenzymes
Diabetes Mellitus

Keywords

  • Cytochrome P-450
  • Diabetes mellitus, experimental
  • Microsomes, liver, kidney
  • Propofol
  • Streptozotocin

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

@article{6ccc827fcaad4160842d36661ca8adfb,
title = "Modulation of cytochrome P-450 dependent monooxygenases in streptozotocin-induced diabetic hamster: I. Effects of propofol on defluorination and cytochrome P-450 activities",
abstract = "Background: Diabetes mellitus could induce polymorphic alterations of metabolic activities of cytochrome P-450 dependent monooxygenases in chemical-induced diabetic animals. The purpose of this study is to define the functional impact of clinical concentrations of propofol on the metabolic activities of cytochrome P-450 in the diabetic animals. Methods: In order to validate the effect of propofol on cytochrome P-450 activities, especially the cytochrome P-450 2E1 and its defluorination activity, we applied NADPH-generating system to measure the metabolizing activities to cytochrome P-450 isozymes of streptozotocin-induced diabetic hamsters within the microsomes preincubated with various concentrations of propofol. The extent of defluorination and activity of cytochrome P-450 2E1 were assessed by reacting the propofol-treated microsomes in NADPH-generating system with enflurane and aniline as substrates respectively. Drug metabolizing activities of cytochrome 1A1, 2B1, and 3A4 were evaluated by metabolizing specific substrates, benzo(a)pyrene, pentoxyresorufin and erythromycin, within the microsomes of diabetic hamsters preincubated with various concentrations of propofol. Results: The hepatic and renal defluorination of influrane was significantly inhibited by 0.05 and 0.10 mM propofol in the microsomes of diabetic hamster (P <0.05). The activities of aniline hydroxylase (cytochrome 2E1), pentoxyresorufin O-dealkylase (cytochrome 2B1) and benzo(a)pyrene hydroxylase (cytochrome 1A1) were inhibited by propofol in a concentration-dependent manner from 0.05 to 0.10 mM. However, propofol showed no significant effect of the erythromycin N-demethylase (cytochrome 3A4) at its concentration of 0.05 - 0.10 mM in the diabetic hamsters. Conclusions: Our data demonstrated that propofol in therapeutic concentrations of 0.05 and 0.10 mM, could inhibit both liver and kidney defluorination and cytochrome P-450's activities of the diabetic hamsters in vitro of different extent. This should remind clinicians of propofol's potential drug-to-drug interactions in the diabetic patients.",
keywords = "Cytochrome P-450, Diabetes mellitus, experimental, Microsomes, liver, kidney, Propofol, Streptozotocin",
author = "Ta-Liang Chen and Huai-Chia Chang and Tyng-Guey Chen and Tai, {Yu Tint} and Ruei-Ming Chen",
year = "2000",
month = "3",
language = "English",
volume = "38",
pages = "15--21",
journal = "Asian Journal of Anesthesiology",
issn = "2468-824X",
publisher = "Elsevier Taiwan LLC",
number = "1",

}

TY - JOUR

T1 - Modulation of cytochrome P-450 dependent monooxygenases in streptozotocin-induced diabetic hamster

T2 - I. Effects of propofol on defluorination and cytochrome P-450 activities

AU - Chen, Ta-Liang

AU - Chang, Huai-Chia

AU - Chen, Tyng-Guey

AU - Tai, Yu Tint

AU - Chen, Ruei-Ming

PY - 2000/3

Y1 - 2000/3

N2 - Background: Diabetes mellitus could induce polymorphic alterations of metabolic activities of cytochrome P-450 dependent monooxygenases in chemical-induced diabetic animals. The purpose of this study is to define the functional impact of clinical concentrations of propofol on the metabolic activities of cytochrome P-450 in the diabetic animals. Methods: In order to validate the effect of propofol on cytochrome P-450 activities, especially the cytochrome P-450 2E1 and its defluorination activity, we applied NADPH-generating system to measure the metabolizing activities to cytochrome P-450 isozymes of streptozotocin-induced diabetic hamsters within the microsomes preincubated with various concentrations of propofol. The extent of defluorination and activity of cytochrome P-450 2E1 were assessed by reacting the propofol-treated microsomes in NADPH-generating system with enflurane and aniline as substrates respectively. Drug metabolizing activities of cytochrome 1A1, 2B1, and 3A4 were evaluated by metabolizing specific substrates, benzo(a)pyrene, pentoxyresorufin and erythromycin, within the microsomes of diabetic hamsters preincubated with various concentrations of propofol. Results: The hepatic and renal defluorination of influrane was significantly inhibited by 0.05 and 0.10 mM propofol in the microsomes of diabetic hamster (P <0.05). The activities of aniline hydroxylase (cytochrome 2E1), pentoxyresorufin O-dealkylase (cytochrome 2B1) and benzo(a)pyrene hydroxylase (cytochrome 1A1) were inhibited by propofol in a concentration-dependent manner from 0.05 to 0.10 mM. However, propofol showed no significant effect of the erythromycin N-demethylase (cytochrome 3A4) at its concentration of 0.05 - 0.10 mM in the diabetic hamsters. Conclusions: Our data demonstrated that propofol in therapeutic concentrations of 0.05 and 0.10 mM, could inhibit both liver and kidney defluorination and cytochrome P-450's activities of the diabetic hamsters in vitro of different extent. This should remind clinicians of propofol's potential drug-to-drug interactions in the diabetic patients.

AB - Background: Diabetes mellitus could induce polymorphic alterations of metabolic activities of cytochrome P-450 dependent monooxygenases in chemical-induced diabetic animals. The purpose of this study is to define the functional impact of clinical concentrations of propofol on the metabolic activities of cytochrome P-450 in the diabetic animals. Methods: In order to validate the effect of propofol on cytochrome P-450 activities, especially the cytochrome P-450 2E1 and its defluorination activity, we applied NADPH-generating system to measure the metabolizing activities to cytochrome P-450 isozymes of streptozotocin-induced diabetic hamsters within the microsomes preincubated with various concentrations of propofol. The extent of defluorination and activity of cytochrome P-450 2E1 were assessed by reacting the propofol-treated microsomes in NADPH-generating system with enflurane and aniline as substrates respectively. Drug metabolizing activities of cytochrome 1A1, 2B1, and 3A4 were evaluated by metabolizing specific substrates, benzo(a)pyrene, pentoxyresorufin and erythromycin, within the microsomes of diabetic hamsters preincubated with various concentrations of propofol. Results: The hepatic and renal defluorination of influrane was significantly inhibited by 0.05 and 0.10 mM propofol in the microsomes of diabetic hamster (P <0.05). The activities of aniline hydroxylase (cytochrome 2E1), pentoxyresorufin O-dealkylase (cytochrome 2B1) and benzo(a)pyrene hydroxylase (cytochrome 1A1) were inhibited by propofol in a concentration-dependent manner from 0.05 to 0.10 mM. However, propofol showed no significant effect of the erythromycin N-demethylase (cytochrome 3A4) at its concentration of 0.05 - 0.10 mM in the diabetic hamsters. Conclusions: Our data demonstrated that propofol in therapeutic concentrations of 0.05 and 0.10 mM, could inhibit both liver and kidney defluorination and cytochrome P-450's activities of the diabetic hamsters in vitro of different extent. This should remind clinicians of propofol's potential drug-to-drug interactions in the diabetic patients.

KW - Cytochrome P-450

KW - Diabetes mellitus, experimental

KW - Microsomes, liver, kidney

KW - Propofol

KW - Streptozotocin

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M3 - Article

C2 - 11000659

AN - SCOPUS:0034039116

VL - 38

SP - 15

EP - 21

JO - Asian Journal of Anesthesiology

JF - Asian Journal of Anesthesiology

SN - 2468-824X

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