Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Esterase activity in rat hepatocytes.

F M Williams1, E Mutch, P G Blain

  • 1Division of Environmental and Occupational Medicine, Medical School, University of Newcastle upon Tyne, U.K.

Biochemical Pharmacology
|February 15, 1991
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Trichloroethylene and its metabolite TaClo lead to degeneration of substantia nigra dopaminergic neurones: Effects in wild type and human A30P mutant α-synuclein mice.

Neuroscience letters·2019
Same author

Steady-state pharmacokinetics of hydroxychloroquine in patients with cutaneous lupus erythematosus.

Lupus·2017
Same author

ON THE EVOLUTION OF HANDLING TIME.

Evolution; international journal of organic evolution·2017
Same author

Erratum to: Diquat causes caspase-independent cell death in SH-SY5Y cells by production of ROS independently of mitochondria.

Archives of toxicology·2015
Same author

Diquat causes caspase-independent cell death in SH-SY5Y cells by production of ROS independently of mitochondria.

Archives of toxicology·2015
Same author

Use of a human skin in vitro model to investigate the influence of 'every-day' clothing and skin surface decontamination on the percutaneous penetration of organophosphates.

Toxicology letters·2014

Rat hepatocytes were used to study drug hydrolysis, revealing significant differences in substrate breakdown rates. Benorylate showed the fastest hydrolysis, while acetylsalicylate and paraoxon were the slowest, highlighting the importance of hepatocyte models for in vivo accuracy.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Hepatology

Background:

  • Drug metabolism and hydrolysis are critical for determining therapeutic efficacy and toxicity.
  • Carboxylesterases in the liver play a significant role in hydrolyzing various xenobiotics.
  • Understanding hydrolysis rates in hepatocytes is crucial for predicting in vivo drug behavior.

Purpose of the Study:

  • To investigate the hydrolysis rates of different xenobiotics using freshly isolated rat hepatocytes.
  • To identify the carboxylesterase isozymes involved in the hydrolysis of specific substrates.
  • To compare the utility of hepatocyte monolayer models versus subcellular fractions for studying hepatic hydrolysis.

Main Methods:

  • Primary rat hepatocytes were isolated and maintained as monolayer cultures.

Related Experiment Videos

  • Hydrolysis rates of acetylsalicylate, benorylate, phenetsal, fluazifop butyl, and paraoxon were measured.
  • Inhibitor studies using paraoxon, BNPP, and physostigmine were conducted to probe enzyme involvement.
  • Substrate uptake into hepatocytes was considered as a potential factor influencing hydrolysis rates.

    • Main Results:

    • Significant variations in hydrolysis rates were observed, with benorylate being hydrolyzed approximately 100 times faster than acetylsalicylate or paraoxon.
    • Phenetsal and fluazifop butyl exhibited hydrolysis rates approximately one-tenth that of benorylate.
    • Inhibitor studies suggested the involvement of distinct carboxylesterase isozymes in the hydrolysis of paraoxon.
    • Acetylsalicylate hydrolysis rate appeared to be influenced by substrate uptake into the hepatocytes.

    Conclusions:

    • Rat hepatocyte monolayers provide a relevant model for studying hepatic xenobiotic hydrolysis, reflecting in vivo conditions more accurately than subcellular fractions.
    • Different carboxylesterase isozymes exhibit substrate specificity, contributing to the varied hydrolysis rates observed.
    • Hepatocyte uptake can be a rate-limiting step for certain substrates, impacting overall hydrolysis.
    • This model system is valuable for assessing drug metabolism and potential drug-drug interactions involving esterase activity.