title: Effect of glutathione administration on hepatic biliary and plasmatic glutathione levels in the rat.
abstract: 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 GSH administration in intact rats.
  
  
  METHODS
  An exteriorized biliary-duodenal fistula was established, and GSH (1 mmol/kg over 2 h) or saline was administered intraperitoneally to rats with or without pretreatment with 5 mmol/kg L-serine borate, an inhibitor of gamma-glutamyltransferase (GGT).
  
  
  RESULTS
  Three hours after GSH administration, biliary GSH efflux and bile flow rose from 104.7 +/- 5.6 to 290.6 +/- 8.6 micrograms/ml bile and from 20.2 +/- 1.3 to 30.2 +/- 2.1 microliters/min, respectively; GSH-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 the hepatic GSH homeostasis after intraperitoneal GSH administration. The activity of hepatic GGT, most likely through degradation of circulating GSH, followed by an increase in cysteine availability, seems to account, at least partially, for the reported effects.
authors.affiliation: Dept. of Internal Medicine, University of Bari, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Vendemiale
authors.forename: V
authors.initials: V
authors.lastname: Palmieri
authors.forename: G
authors.initials: G
authors.lastname: Palasciano
authors.forename: E
authors.initials: E
authors.lastname: Altomare
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism*; D001658:Biliary Fistula / Q000378:metabolism; D001881:Borates / Q000494:pharmacology; D004378:Duodenal Diseases / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism* / Q000494:pharmacology*; D006706:Homeostasis; D007412:Intestinal Fistula / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012694:Serine / Q000494:pharmacology; D005723:gamma-Glutamyltransferase / Q000037:antagonists & inhibitors / Q000502:physiology
chemical_list: D001881:Borates; C040900:serine-borate complex; D012694:Serine; D005723:gamma-Glutamyltransferase; D005978:Glutathione