Glutathione Conjugation and Mercapturic Acid Formation in the Developing Rat, in vivo and in vitro

Abstract

1. The levels of GSH-S-epoxidetransferase (GSH-S-transferase E, EC 2.5.1.18), γ-glutamyl transpeptidase (EC 2.3.2.2) and S-substituted cysteine N-acetyltransferase have been measured in the liver and kidney of neonatal to adult rats.

2. GSH-S-epoxidetransferase and S-substituted cysteine N-acetyltransferase activities were less than 10% of the adult values in neonatal rats, rising gradually to reach adult values at about 40 days of age. Renal γ-glutamyl transpeptidase activity was 27% of the adult value 2 days after birth and increased after 15 days reaching adult levels by 40 days.

3. The percentages of the doses of 1,2-epoxy-3-(p-nitrophenoxy)propane (ENPP) and of 1,2-epoxybutane, administered at the same dose level to rats aged 4 days to adult, excreted as the corresponding mercapturic acids in 24 h, were not significantly different.

4. Adult and 10 day old rats dosed at the same dose level with ENPP excreted N-acetyl-S-[2-hydroxy-3-(p-nitrophenoxy)propyl]-L-cysteine (ENPPMA) at the same rate.

5. In addition to ENPP-MA, dosed rats under 13 days of age excreted the corresponding substituted cysteine.

6. The correlation between results in vitro and in vivo is discussed.