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

Abstract

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. Steady-state levels of cysteine also decreased in both tissues with galactose feeding, and the magnitude of decrease was higher in the liver as compared to the lens. The rate of cysteine uptake in hepatocytes isolated from galactose-fed guinea pigs was significantly lower for the cysteine concentrations studied (10 µM to 1 µM) as compared to control uptake. The decreased steady-state liver GSH and cysteine levels in galactose-fed guinea pigs caused a significant decrease in plasma (and aqueous) GSH concentrations. CONCLUSIONS. We concluded that the decrease in lens GSH due to galactose occurs without alterations in the capacity of GSH synthesis, in either lens or liver. It is suggested that decreased hepatic GSH, resulting in reduced plasma GSH levels due to decreased GSH efflux into plasma, may contribute to impairment in plasma to lens GSH transport with galactose. Thus, the functional role of recently identified lens GSH transporters, particularly that of Na + -dependent GSH transporter, in galactose-induced cataract formation will be worthy of investigation.