Depletion of glutathione by the hepatotoxins paracetamol and bromobenzene, and their non-hepatotoxic analogues, in a fortified liver microsomal system.
The proposal that liver microsome mixed-function oxidase (MFO)-mediated generation of reactive metabolites may be detected by depletion of reduced glutathione (GSH) added to a fortified microsome incubation containing substrate has been investigated. Paracetamol, 3-hydroxyacetanilide, bromobenzene and p-bromophenol were used as substrates for a MFO-mediated depletion of GSH in vitro. Studies involving modulation of the extent of GSH depletion in vitro and comparison with published findings indicated that metabolism-mediated depletion of GSH in a fortified liver microsome incubation correlated with covalent binding of reactive metabolites but did not correlate well with the ability of compounds to cause GSH depletion in vivo or liver damage.
Garle
M J
MJ
Department of Physiology and Pharmacology, The University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, UK.
Khan
J
J
Fry
J R
JR