Propofol inhibits renal cytochrome P450 activity and enflurane defluorination in vitro in hamsters

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Abstract

Purpose: To determine the effect of propofol on renal cytochrome P450 activity and defluorination of enflurane. Methods: Renal microsomes were prepared by homogenization and differential centrifugation from pooled hamster kidneys. Defluorination of enflurane was assessed by measuring free fluoride metabolites after reacting enflurane with renal microsomes incubated with various concentrations, 0.05 - 1.0 mmol·L-1 propofol in the NADPH-generating system. Drug metabolizing activities of renal cytochrome P450 mono-oxygenase enzymes were evaluated within microsomes preincubated with propofol and reacted with the specific marker substrates, aniline, benzo(a)pyrene, erythromycin and pentoxyresorufin, for cytochrome P450 2E1, 1A1, 3A4 and 2B1, respectively. Results: Renal defluorination of enflurane was inhibited by clinical concentrations, 0.05 mmol·L-1 of propofol (P <0.05). Dose-dependent inhibition of defluorination, aniline and benzo(a)pyrene hydroxylase within kidney microsomes was related to propofol concentration. Propofol demonstrated a profound inhibition of renal pentoxyresorufin dealkylase activity even at low concentrations, 0.05 mmol·L-1 (P <0.01). Propofol did not exhibit inhibition of erythromycin N-demethylation of kidney microsomes except at high concentration, 1.0 mmol·L-1. Spectral analyses of key coenzymes of renal cytochrome P450 monooxygenase, cytochrome b5 and cytochrome c reductase, demonstrated an inhibitior when incubated with high concentrations of propofol (P <0.05). Conclusion: In an in vitro study in an NADPH-generating system of hamster kidney microsomes, propofol, in clinical concentrations, exhibited a broad-spectrum of inhibition to renal monooxygenase activities and enflurane defluorination.

Original languageEnglish
Pages (from-to)680-686
Number of pages7
JournalCanadian Journal of Anesthesia
Volume47
Issue number7
Publication statusPublished - 2000

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Enflurane
Propofol
Cricetinae
Cytochrome P-450 Enzyme System
Kidney
Microsomes
Erythromycin
Mixed Function Oxygenases
NADP
In Vitro Techniques
Benzopyrene Hydroxylase
Cytochrome P-450 CYP2B1
Cytochrome Reductases
Cytochromes b5
Cytochrome P-450 CYP2E1
Oxygenases
Benzo(a)pyrene
Coenzymes
Cytochromes c
Fluorides

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

@article{7f4918f394ae4f46a7e2968f49aba7bd,
title = "Propofol inhibits renal cytochrome P450 activity and enflurane defluorination in vitro in hamsters",
abstract = "Purpose: To determine the effect of propofol on renal cytochrome P450 activity and defluorination of enflurane. Methods: Renal microsomes were prepared by homogenization and differential centrifugation from pooled hamster kidneys. Defluorination of enflurane was assessed by measuring free fluoride metabolites after reacting enflurane with renal microsomes incubated with various concentrations, 0.05 - 1.0 mmol·L-1 propofol in the NADPH-generating system. Drug metabolizing activities of renal cytochrome P450 mono-oxygenase enzymes were evaluated within microsomes preincubated with propofol and reacted with the specific marker substrates, aniline, benzo(a)pyrene, erythromycin and pentoxyresorufin, for cytochrome P450 2E1, 1A1, 3A4 and 2B1, respectively. Results: Renal defluorination of enflurane was inhibited by clinical concentrations, 0.05 mmol·L-1 of propofol (P <0.05). Dose-dependent inhibition of defluorination, aniline and benzo(a)pyrene hydroxylase within kidney microsomes was related to propofol concentration. Propofol demonstrated a profound inhibition of renal pentoxyresorufin dealkylase activity even at low concentrations, 0.05 mmol·L-1 (P <0.01). Propofol did not exhibit inhibition of erythromycin N-demethylation of kidney microsomes except at high concentration, 1.0 mmol·L-1. Spectral analyses of key coenzymes of renal cytochrome P450 monooxygenase, cytochrome b5 and cytochrome c reductase, demonstrated an inhibitior when incubated with high concentrations of propofol (P <0.05). Conclusion: In an in vitro study in an NADPH-generating system of hamster kidney microsomes, propofol, in clinical concentrations, exhibited a broad-spectrum of inhibition to renal monooxygenase activities and enflurane defluorination.",
author = "Ta-Liang Chen and Tyng-Guey Chen and Yu-Ting Tai and Huai-Chia Chang and Ruei-Ming Chen and Lin, {C. J.} and Tzuu-Huei Ueng",
year = "2000",
language = "English",
volume = "47",
pages = "680--686",
journal = "Canadian Journal of Anaesthesia",
issn = "0832-610X",
publisher = "Springer New York",
number = "7",

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TY - JOUR

T1 - Propofol inhibits renal cytochrome P450 activity and enflurane defluorination in vitro in hamsters

AU - Chen, Ta-Liang

AU - Chen, Tyng-Guey

AU - Tai, Yu-Ting

AU - Chang, Huai-Chia

AU - Chen, Ruei-Ming

AU - Lin, C. J.

AU - Ueng, Tzuu-Huei

PY - 2000

Y1 - 2000

N2 - Purpose: To determine the effect of propofol on renal cytochrome P450 activity and defluorination of enflurane. Methods: Renal microsomes were prepared by homogenization and differential centrifugation from pooled hamster kidneys. Defluorination of enflurane was assessed by measuring free fluoride metabolites after reacting enflurane with renal microsomes incubated with various concentrations, 0.05 - 1.0 mmol·L-1 propofol in the NADPH-generating system. Drug metabolizing activities of renal cytochrome P450 mono-oxygenase enzymes were evaluated within microsomes preincubated with propofol and reacted with the specific marker substrates, aniline, benzo(a)pyrene, erythromycin and pentoxyresorufin, for cytochrome P450 2E1, 1A1, 3A4 and 2B1, respectively. Results: Renal defluorination of enflurane was inhibited by clinical concentrations, 0.05 mmol·L-1 of propofol (P <0.05). Dose-dependent inhibition of defluorination, aniline and benzo(a)pyrene hydroxylase within kidney microsomes was related to propofol concentration. Propofol demonstrated a profound inhibition of renal pentoxyresorufin dealkylase activity even at low concentrations, 0.05 mmol·L-1 (P <0.01). Propofol did not exhibit inhibition of erythromycin N-demethylation of kidney microsomes except at high concentration, 1.0 mmol·L-1. Spectral analyses of key coenzymes of renal cytochrome P450 monooxygenase, cytochrome b5 and cytochrome c reductase, demonstrated an inhibitior when incubated with high concentrations of propofol (P <0.05). Conclusion: In an in vitro study in an NADPH-generating system of hamster kidney microsomes, propofol, in clinical concentrations, exhibited a broad-spectrum of inhibition to renal monooxygenase activities and enflurane defluorination.

AB - Purpose: To determine the effect of propofol on renal cytochrome P450 activity and defluorination of enflurane. Methods: Renal microsomes were prepared by homogenization and differential centrifugation from pooled hamster kidneys. Defluorination of enflurane was assessed by measuring free fluoride metabolites after reacting enflurane with renal microsomes incubated with various concentrations, 0.05 - 1.0 mmol·L-1 propofol in the NADPH-generating system. Drug metabolizing activities of renal cytochrome P450 mono-oxygenase enzymes were evaluated within microsomes preincubated with propofol and reacted with the specific marker substrates, aniline, benzo(a)pyrene, erythromycin and pentoxyresorufin, for cytochrome P450 2E1, 1A1, 3A4 and 2B1, respectively. Results: Renal defluorination of enflurane was inhibited by clinical concentrations, 0.05 mmol·L-1 of propofol (P <0.05). Dose-dependent inhibition of defluorination, aniline and benzo(a)pyrene hydroxylase within kidney microsomes was related to propofol concentration. Propofol demonstrated a profound inhibition of renal pentoxyresorufin dealkylase activity even at low concentrations, 0.05 mmol·L-1 (P <0.01). Propofol did not exhibit inhibition of erythromycin N-demethylation of kidney microsomes except at high concentration, 1.0 mmol·L-1. Spectral analyses of key coenzymes of renal cytochrome P450 monooxygenase, cytochrome b5 and cytochrome c reductase, demonstrated an inhibitior when incubated with high concentrations of propofol (P <0.05). Conclusion: In an in vitro study in an NADPH-generating system of hamster kidney microsomes, propofol, in clinical concentrations, exhibited a broad-spectrum of inhibition to renal monooxygenase activities and enflurane defluorination.

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