[Effect of pyrazolone derivatives on the level of reduced glutathione in rat liver].

The pyrazolone derivatives aminophenazone, phenazone, and propyphenazone are capable of decreasing reduced glutathione (GSH) in the liver after a single dose of 3 mmol/kg. The strongest effect is seen in female animals treated with propyphenazone. The depletion can be caused by (1) consumption during phase I of biotransformation, if reactive side products are inactivated by GSH-peroxidase, (2) consumption during phase II of biotransformation, if reactive metabolites are conjugated with GSH by GSH-S-transferases, (3) consumption of NADPH during the biotransformation processes of the pyrazolones as such, (4) influence on enzymes responsible for the synthesis of GSH. After repeated administration only aminophenazone decreases the hepatic content of GSH. Pretreatment with phenobarbital only prevents the propyphenazone-dependent GSH-depletion, but cobaltous chloride has no effect. GSH-depletion is regarded as one of the primary events in liver damage, following pyrazolone administration.