Increased sinusoidal efflux of reduced and oxidized glutathione in rats with endotoxin/D-galactosamine hepatitis.

Abstract

The changes in the concentrations of reduced (GSH) and oxidized glutathione (GSSG) in the plasma as well as in the liver were investigated in rats with endotoxin hepatitis. Hepatitis was induced by intraperitoneal co-administration of small doses of Escherichia coli endotoxin and D-galactosamine. In the liver, the concentration of GSH decreased and that of GSSG increased 12 hr later. In the plasma taken from the right atrium, the concentration of both GSH and GSSG increased. The GSH/GSSG ratio in the plasma decreased, as it did in the liver. The net sinusoidal efflux of GSH and GSSG from the liver was calculated by subtracting their concentrations in plasma of the infrahepatic, suprarenal inferior vena cava from those of the suprahepatic inferior vena cava. The efflux started to increase as early as 2-4 hr after the injection of the toxins. In contrast, a leakage of alanine aminotransferase, an elongation of prothrombin time, an inhibition of starvation ketosis, and an increase in serum concentration of total bilirubin were detected as late as 6-8 hr after the injection. We conclude that endotoxin/D-galactosamine hepatitis induced an increase in plasma concentrations of GSH as well as GSSG by increasing the efflux of these peptides from the liver, and that changes in plasma glutathione status might be useful and sensitive markers for liver damage.