EFFECT OF GLUTATHIONE ADMINISTRATION ON HEPATIC BILIARY AND PLASMATICGLUTATHIONE LEVELS IN THE RAT

Background: Since the effect of exogenous glutathione (GSH) on overall hepatic GSH homeostasis is not known, the present study investigated the changes in the hepatic, biliary, and plasmatic GSH levels during G SH administration in intact rats. Methods: An exteriorized biliary-duo denal fistula was established, and GSH (1 mmol/kg over 2 h) or saline was administered intraperitoneally to rats with or without pretreatmen t with 5 mmol/kg L-serine berate, an inhibitor of gamma-glutamyltransf erase (GGT). Results: Three hours after GSH administration, biliary GS H efflux and bile flow rose from 104.7 +/- 5.6 to 290.6 +/- 8.6 mu g/m l bile and from 20.2 +/- 1.3 to 30.2 +/- 2.1 mu l/min, respectively; G SH-treated rats also showed increased liver (35%) and posthepatic Vein plasma (68%) GSH concentrations compared with controls. By contrast, in rats pretreated with the GGT inhibitor GSH administration appeared to be devoid of any effect, except for a modest biliary GSH increase. Conclusions: This study indicates that significant changes occur in th e hepatic GSH homeostasis after intraperitoneal GSH administration. Th e activity of hepatic GGT, most likely through degradation of circulat ing GSH, followed by an increase in cysteine availability, seems to ac count, at least partially, for the reported effects.