Ontogenetic changes in hepatic glutathione system (synthesis, catabolism, export) of male Uje:WIST rats.

The age-courses of concentrations of reduced (GSH) and oxidized (GSSG) glutathione, of GSH synthesizing enzyme activities, of glutathione S-transferase (GST), of GSSG-reductase (GR) and of biliary GSH and GSSG export were measured in livers from male Uje:WIST rats. Additionally, the age-courses of plasma GSH and GSSG concentrations were investigated. The hepatic level of GSH showed a biphasic pattern with a first maximum immediately after birth and a small second peak at the 50th day of life. The GSSG level increased continuously up to day 60 of life. The cytosolic GSH synthesizing enzyme activities showed diverse developmental patterns indicating different regulation principles. The hepatic activity of GR was relatively constant in the different age groups after birth. The GST activity (with o-dinitrobenzene as substrate) was relatively low at birth (about 30% of the maximum measured at day 60 of life). The maximum of GSH plasma level was found at birth. With increasing age a significant decrease in this level was observed. The excretion rate of total GSH (GSH + 2 GSSG) in bile was found to increase about 9-fold between 15 and 105 days of age. The results indicate that changes of hepatic GSH concentration with age are dependent on numerous factors. The balance between synthesis, catabolism and export is important for the maintenance of this level.