Liver and lens glutathione and cysteine regulation in galactose-fed guinea pigs

PURPOSE. To study the mechanism of lenticular glutathione (GSH) depletion in galactose-fed guinea pigs, with particular reference to correlations between liver and lens GSH, precursor (cysteine) status and GSH synthetic capacities. METHODS. Guinea pigs in the ad libitum-fed state were fed powdered guinea pig chow containing 50% galactose for 3 and 14–16 days. Plasma GSH and GSH levels in lens, liver and freshly isolated hepatocytes were determined. Maximal rates of GSH synthesis in liver and lens as well as steady state levels of precursor cysteine were also determined. In separate experiments, linear rate of 35 S-cysteine uptake was studied in isolated hepatocytes from control and galactose-fed animals. Lens and liver GSH decreased significantly with galactose feeding. Hepatic GSH showed a dramatic decrease (~83%) as early as day 3 whereas ~43% decrease was observed in lens. The maximal GSH synthetic rates (GSH-SR) in the whole lens and liver on days 3 and 14–16 were not different from those of controls....