Ontogeny of hepatobiliary secretion: role of glutathione

The ontogeny of hepatic synthesis and biliary secretion of glutathione was characterized and correlated with hepatic gamma glutamyl transpeptidase, bile flow rate, biliary bile acids and amino acids in Sprague-Dawley rats at 18 days of gestation and postnatally at ages 7, 14, 21, 28 and 54 days. Bile was collected by bile duct cannulation under intraperitoneal anesthesia with nembutal/ketamine. Glutathione, gamma glutamyl transpeptidase and bile acids were analyzed enzymatically and amino acids by high-performance liquid chromatography using established methods. Hepatic glutathione was low in the fetus, but increased to approximate adult levels by 7 days postnatally (2.77 mumol/gm liver). Hepatic gamma glutamyl transpeptidase activity, high in the fetus, declined to adult levels by day 7 (0.03 mumol/mg protein). In contrast, significant efflux of glutathione and its constituent amino acids into bile did not occur until weaning (21 days of age). During weaning, there was a fivefold increase in the biliary glutathione and with a twofold increase in bile flow rate. Biliary bile acids concentration remained constant throughout development, with only a 30% to 50% increase in its secretion rate. The data suggest that the developmentally related increase in bile flow rate was principally a result of the increase in bile acid independent flow from 1.1 microliters/(min.100 gm body wt) in the suckling to 4.3 microliters/(min.100 gm body wt) in the post-weanling animal.(ABSTRACT TRUNCATED AT 250 WORDS)