Glutathione metabolism was studied in rat liver during diethylnitrosamine (DEN) carcinogenesis. Some studies were also made in foetal rat liver, Endogenous GSH and non-protein thiols concentrations are increased in DEN-treated rats when compared to non-treated rats but no differences were found in cysteine, total thiols and protein thiols concentration. In foetal liver GSH concentration is only 35% of that in DEN-treated rat liver. The activities of several enzymes involved in glutathione metabolism are changed in DEN-treated rats. γ-Glutamyl transferase activity and cysteine formation from GSH by liver homogenates is increased sevenfold. γ-Glutamylcysteine synthetase activity, initial rate of [35S]cysteine incorporation in γ-glutamylcysteine and initial rate of GSH formation from [35S]cysteine are increased two-fold. Cytosolic GSH S-transferase activity is increased twofold in DEN-treated rats and so GSH S-conjugates concentration is probably also increased. In foetal rat liver γ-glutamyl transferase activity is about the same but γ-glutamylcysteine synthetase activity is only 10% of that in DEN-treated rat liver. The increased GSH concentration in DEN-treated rat liver is probably due to the simultaneous increase in the activities of γ-glutamyl transferase and γ-glutamylcysteine synthetase. Blood plasma total glutathione is increased 1.4 times in DEN-treated rats, but no differences are found in GSH hepatic arteriovenous gradient. This associated with the increased γ-glutamyl transferase activity suggests that sinusoidal GSH efflux is increased in DEN-treated rats.
Marinho, H. S., Baptista, M., & Pinto, R. E. (1997). Glutathione metabolism in hepatomous liver of rats treated with diethylnitrosamine. Biochimica et Biophysica Acta - Molecular Basis of Disease, 1360(2), 157–168. https://doi.org/10.1016/S0925-4439(96)00075-0