Induction of glutathione S-transferase isoenzymes in mouse liver by 5-(2-pyrazynl)-4-methyl-1,2-dithiole-3-thione (oltipraz).
Treatment of mice with a single dose of oltipraz (OPZ) at 200 mg/kg led to a significant (P less than 0.05) increase in hepatic cytosolic glutathione S-transferase (GST) activity and content. GST activity monitored with 1,2-dichloro-4-nitrobenzene was increased 3.8-fold 3 days after treatment, suggesting the induction of mu class isoenzymes. Ethacrynic acid, a marker for pi class isoforms, showed only a slight increase in GST activity while no induction was observed with cumene hydroperoxide, an indicator for the alpha class. The increase in mu class isoenzymes was further confirmed by separation of the mouse liver affinity purified GST by chromatofocusing and also by resolving the GST subunits by reverse-phase high performance liquid chromatographic procedures. Therefore, OPZ induces mainly the mu class isoenzymes in mouse hepatic tissues.
Nare
B
B
Institute of Parasitology, McGill University, Ste-Anne de Bellevue, Quebec, Canada.
Smith
J M
JM
Prichard
R K
RK
D000818:Animals; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D004790:Enzyme Induction / Q000187:drug effects; D005982:Glutathione Transferase / Q000096:biosynthesis* / Q000302:isolation & purification; D007527:Isoenzymes / Q000096:biosynthesis* / Q000302:isolation & purification; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D011719:Pyrazines / Q000494:pharmacology*; D012556:Schistosomicides / Q000494:pharmacology*; D013379:Substrate Specificity; D013871:Thiones; D013876:Thiophenes
D007527:Isoenzymes; D011719:Pyrazines; D012556:Schistosomicides; D013871:Thiones; D013876:Thiophenes; C026209:oltipraz; D005982:Glutathione Transferase