Metabolic changes in glutathione and metallothionein in newborn rat liver

Metallothionein (MT) and glutathione (GSH) both contain 30% cysteine and they have distinct developmental profiles in perinatal rat liver. The metabolic relationships between these two cysteine pools were investigated in newborn rats under various experimental conditions. Injection of 2-day-old rat pups with buthionine sulfoximine, phorone or diethylmaleate decreased hepatic GSH levels without any change in high basal levels of MT or zinc. Similarly injection of L-oxothiazolidine carboxylate increased hepatic GSH levels but no changes in MT or zinc levels were observed. Administration of buthionine sulfoximine in drinking water to pregnant rats from day 14 of gestation decreased hepatic GSH concentrations in both the dams and pups with little change observed in neonatal hepatic zinc and MT levels or in gamma-glutamyltranspeptidase activity. The induction of MT synthesis by zinc salts in newborn rats was not affected by the in utero reduction of GSH levels. Although maternal hepatic GSH levels can be decreased by a sulfhydryl-deficient diet, no changes were observed in GSH, MT or zinc levels in newborn rat liver. Reduction of perinatal hepatic MT levels by in utero zinc deficiency had little effect on GSH levels. However, inhibition of the cystathionase pathway in newborn rats with propargylglycine decreased hepatic levels of MT, zinc and GSH. The results suggest that whereas there is little interaction between these two pools of cysteine, inhibition of cystathionase activity can decrease hepatic concentrations of both GSH and MT.