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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.

The occurrence of pigment and cholesterol calculi was studied in 45 patients with concrements in the gallbladder but no calculi in the common or intrahepatic bile ducts. Twenty-one of the patients had juxtapapillary duodenal diverticula diagnosed by duodenoscopy. Twenty-four patients had no diverticula. The classification of the calculi as pigment stones or cholesterol stones was based on quantitative determination of the cholesterol contents. Calculi with a cholesterol content of less than 25% were classified as pigment stones; calculi with a cholesterol content of more than 25% were classified as cholesterol stones. All pigment stones had a cholesterol content of less than 20%. With the exception of four patients the cholesterol content was over 70% in all cholesterol stones. Twelve of the 21 patients with were classified as pigment stones; calculi with a cholesterol content of more than 25% were classified as cholesterol stones. All pigment stones had a cholesterol content of less than 20%. With the exception of four patients the cholesterol content was over 70% in all cholesterol stones. Twelve of the 21 patients with were classified as pigment stones; calculi with a cholesterol content of more than 25% were classified as cholesterol stones. All pigment stones had a cholesterol content of less than 20%. With the exception of four patients the cholesterol content was over 70% in all cholesterol stones. Twelve of the 21 patients with diverticula had pigment stones, whereas only 1 of the 24 patients without diverticula had pigment calculi, a difference that was statistically significant (p less than 0.01).

Patients with juxtapapillary duodenal diverticula have an increased occurrence of calcium bilirubinate gallstones. One possible hypothesis to explain this observation is enzymatic deconjugation of bilirubin conjugates in the bile. Beta-glucuronidase of human or bacterial origin may lead to deconjugation of the bilirubin glucuronides in bile. This, in turn, may increase the amounts of unconjugated, water-insoluble bilirubin which can precipitate as calcium bilirubinate, the main component of brown pigment stones. In this study we compared gallstone patients with and without duodenal diverticula treated with endoscopic papillotomy. Increased occurrence of bacteria producing beta-glucuronidase (p less than 0.01) and increased activity of bacterial beta-glucuronidase (pH 7.0) in the bile itself (p less than 0.01) were found in patients with duodenal diverticula. When the activity of the enzyme at pH 4.5, the optimum of the human enzyme, was measured, no such difference was found. The results support the hypothesis of bacterial glucuronidase as an etiologic factor in pigment gallstone disease in patients with duodenal diverticula. The high activity of bacterial enzyme found in the bile in some patients without diverticula suggests bacteria as an etiologic factor, independent of the presence of diverticula.