Decreased production of glutathione in patients with cirrhosis

Studies in animals have demonstrated the central role of the liver in regulating the circulating pool of glutathione (GSH). Most of the hepatic GSH production is released into blood and most of the circulating GSH originates in the liver. We have estimated the production of GSH in eight healthy volunteers and eight patients with cirrhosis by an analysis of the kinetics of plasma GSH. The basal plasma concentrations of free GSH were 9.3 +/- 2.4 microM in healthy volunteers and 3.6 +/- 1.1 microM in cirrhotics (P less than 0.001), and the concentrations of total GSH 16.6 +/- 6.2 microM in control subjects and 7.1 +/- 2.6 microM in cirrhotics (P less than 0.002). The concentration of GSH in the circulating pool depends on the input of GSH into this compartment and is inversely proportional to the volume of distribution of GSH (Vd) and to the fractional rate of elimination of GSH from plasma (kel). Assuming that the kinetics of endogenously produced and exogenously administered GSH are identical, Vd and kel can be calculated from the plasma concentration-time curve of a single i.v. injection of GSH. Both Vd (0.100 +/- 0.044 l kg-1 in controls and 0.131 +/- 0.043 l kg-1 in cirrhotics) and kel (0.2718 +/- 0.0555 min-1 in controls and 0.2912 +/- 0.0781 min-1 in cirrhotics) were identical in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)