Hepatic export of glutathione and uptake of constituent amino acids, glutamate and cysteine, in broilers in vivo

This study was conducted to document the glutathione (GSH) cycle (interorgan circulation of GSH) in broilers in vivo. Two experiments were conducted on 36 anesthetized male broilers (n = 6 per treatment) implanted with cannulae in the carotid artery, hepatic portal, and hepatic veins. Plasma GSH, glutamate, cysteine, cystine, and cysteinylglycine levels in each vessel were monitored following a bolus injection [Experiment (Exp.) 1] or 30 min continuous infusion (Exp. 2) of GSH, or a gamma-glutamyltranspeptidase inhibitor (AT125) into the hepatic portal vein. Controls received saline alone. The GSH and AT125 treatments were used to determine the effect of increasing the prehepatic GSH load and of inhibiting systemic GSH degradation, respectively, on the GSH cycle. Hepatic export of GSH was clearly evident in all three treatment groups in both experiments (Exp.). The GSH and AT125 treatments raised amino acid levels in some or all of the vessels, whereas cysteinylglycine was elevated by AT125 and depressed by the GSH treatment compared to Controls. Hepatic uptake of glutamate, cysteine, and/or cystine was observed in Controls and GSH-treated birds, but not in birds given AT125 (Exp. 2). Neither hepatic export nor uptake of cysteinylglycine was observed in any treatment group. The results clearly demonstrate the ability of the avian liver to export GSH into the general circulation despite alterations that might arise from changes in extra-hepatic ability to utilize GSH or its constituent amino acids.