CARBON-TETRACHLORIDE INCREASES SINUSOIDAL EFFLUX OF REDUCED AND OXIDIZED GLUTATHIONE IN RATS

To elucidate the significance of the changes in plasma glutathione con centrations associated with carbon tetrachloride (CCl4)-induced liver damage, the changes in the concentrations of reduced (GSH) and oxidize d glutathione (GSSG) in plasma as well as in the liver were investigat ed in rats. In the liver, the concentration of GSH decreased, and that of GSSG increased 24 hr after the intraperitoneal administration of C Cl4. In the right atrial plasma, the concentration of both GSH and GSS G increased. The GSH/GSSG ratio in the plasma decreased as did that in the liver. The net sinusoidal efflux of GSH and GSSG from the liver w as calculated by subtracting their concentrations in plasma of the inf rahepatic inferior vena cava from those of the suprahepatic inferior v ena cava. The net efflux of GSH and GSSG started to increase as early as 3-6 hr after CCl4 administration, and reached a plateau 6 and 24 hr after CCl4 administration, respectively. On the other hand, an elonga tion of prothrombin time and leakage of alanine aminotransferase reach ed a maximum 24 and 48 hr after CCl4 administration, respectively. Vac uolization in the centri-lobular region and inflammatory infiltration started 3 and 6 hr after CCl4 administration, respectively, and progre ssed for 48 hr. These results suggest that CCl4 induced an increase in plasma concentrations of GSH as well as GSSG by increasing their effl ux from the liver, and that the changes in plasma glutathione status m ight be a useful and sensitive marker for CCl4-induced liver damage.