Metabolism and biliary excretion of sulfobromophthalein in vitamin a deficiency

Vitamin A deficiency in rats significantly increased hepatic glutathione S-aryltransferase activities measured in vitro against 1,2-dichloro-4-nitrobenzene (DCNB) and sulfobromophthalein (BSP). These changes were accompanied by a decrease in hepatic glutathione reductase activity in the deficient animals, but there were no alterations in either oxidized glutathione (GSSG) levels or the ratio of reduced glutathione (GSH) to GSSG in the liver. The relation between plasma BSP clearance, biliary BSP excretion, and the enzymatic conjugation rate of the dye were examined. Plasma clearance, hepatic uptake and hepatic storage of BSP were reduced in vitamin A deficient animals. Biliary concentration, excretion rate and cumulative excretion of BSP, on the other hand, were increased in these animals. The increases in these variables were due predominantly to increased formation of conjugated BSP. It is concluded, therefore, that the rate of the enzymatic conjugation of BSP with GSH is a rate-limiting step in the biliary excretion of the dye.