Induction of glutathione s-transferase isoenzymes in mouse liver by 5-(2-pyrazynl)-4-methyl-1,2-dithiole-3-thione (oltipraz)

Abstract

Treatment of mice with a single dose of oltipraz (OPZ) at 200 mg/kg led to a significant (P < 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 μ class isoenzymes. Ethacrynic acid, a marker for π class isoforms, showed only a slight increase in GST activity while no induction was observed with cumene hydroperoxide, an indicator for the α class. The increase in μ 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 chromatographie procedures. Therefore, OPZ induces mainly the μ class isoenzymes in mouse hepatic tissues.