EFFECTS OF INHIBITION OF CYSTATHIONASE ACTIVITY ON GLUTATHIONE AND METALLOTHIONEIN LEVELS IN THE ADULT-RAT

The effects of alterations in sulfur metabolism on hepatic and renal metallothionein and glutathione metabolism were studied in the adult rat using inhibition of two enzymes of these pathways, hepatic cystathionase and renal gamma-glutamyl transpeptidase. Rats were fed a diet containing both methionine (0.66%) and cystine (0.20%) for 1 week before receiving three consecutive daily intraperitoneal injections of propargylglycine, a selective cystathionase inhibitor, at various doses (2.5-375-mu-mol/kg). When hepatic cystathionase was inhibited greater than 90% (greater-than-or-equal-to 50-mu-mol propargylglycine/kg), renal and hepatic metallothionein and hepatic glutathione were unaltered except at the highest dose. On the other hand, renal glutathione was increased two-fold with a concomitant decrease in renal gamma-glutamyl transpeptidase activity (50% of control). In another experiment, when renal gamma-glutamyl transpeptidase was inhibited greater than 90% with three consecutive daily injections of acivicin, a selective gamma-glutamyl transpeptidase inhibitor (10 mg/kg IP), renal glutathione content was unaltered while hepatic glutathione was decreased. Renal and hepatic metallothionein were not changed. Thus, the cysteine pools for metallothionein and glutathione appear unrelated under the present experimental conditions. In addition, following either propargylglycine or acivicin injections, renal and hepatic glutathione pools appear to be altered differently. These results suggest that renal glutathione may be preferentially maintained even when hepatic glutathione is decreased.