Detection of reactive metabolites in vitro.

Abstract:

:The ability of 27 compounds to mediate depletion of glutathione (GSH) in a fortified liver microsome incubation via production of reactive metabolites generated by microsomal mono-oxygenase (MMO) metabolism has been studied. The majority of compounds tested of this type were positive in this assay, with the exception of iproniazid and naphthalene. Thioacetamide, the reactive metabolite of which binds via lysine residues, was negative. Acrolein and hexachlorobutadiene produced depletion in the absence of prior activation, as did menadione but for which enzyme induction increased the magnitude of depletion. Allyl alcohol produced MMO-mediated depletion of GSH. Some depletion of GSH occurred in the presence of common substrates of the MMO system. It is suggested that this depletion assay may be a valid test for detection of reactive metabolites generated by MMO metabolism.

journal_name

Toxicology

journal_title

Toxicology

authors

Garle MJ,Fry JR

doi

10.1016/0300-483x(89)90082-6

subject

Has Abstract

pub_date

1989-01-01 00:00:00

pages

101-10

issue

1

eissn

0300-483X

issn

1879-3185

pii

0300-483X(89)90082-6

journal_volume

54

pub_type

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