Hepatic
glutathione turnover and the efflux of
glutathione from the liver into bile and blood were measured in male Sprague-Dawley rats in vivo. In fed rats the efflux of
glutathione into blood, calculated from the hepatic arteriovenous concentration gradient and hepatic blood flow, amounted to 12.4 +/- 1.4 nmoles min X gm liver. Together with the excretion of
glutathione into bile (3.4 +/- 0.4 nmoles per min X gm liver) total efflux accounted for the hepatic turnover of
glutathione of 15.2 +/- 0.9 nmoles per min X gm liver. Fasting animals for 48 hr markedly increased hepatic
glutathione turnover to 26.4 +/- 1.2 nmoles per min X gm liver. Increased efflux into blood rather than increased intrahepatic catabolism accounted for this increased turnover. The systemic clearance of
glutathione was 3.22 +/- 0.51 ml per min X 100 gm
body weight. The efflux of
glutathione from liver therefore was calculated to contribute over 90% of total
glutathione inflow into the circulation, as determined from the clearance and the arterial concentration of
glutathione. Thus, the liver is the major source of plasma
glutathione, and turnover of hepatic
glutathione in the basal state is accounted for almost entirely by efflux of
glutathione from the liver. During fasting, the plasma clearance of exogenous
glutathione increased to 5.32 +/- 0.35 ml per min X 100 gm
body weight, and the utilization of
methionine for
glutathione synthesis increased markedly. The increased extrahepatic catabolism during fasting results in a decrease in plasma
glutathione, which in turn may account for the observed increase in sinusoidal
glutathione efflux with concomitant stimulation of the rate of hepatic
glutathione turnover and of synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)