Lithocholic acid-induced cholestasis in newborn rats

Abstract

Susceptibility to lithocholic acid-induced cholestasis was examined in developing rats aged 14, 21 and 70 days. After bile duct cannulation, bile was collected for 30 min prior to, and 120 min following an i.v. injection of [14C]lithocholic acid (LCA). The liver weight/body weight ratio of newborns was significantly smaller than that of adults (3.13 +/- 0.09 at 14 days vs. 4.76 +/- 0.20 at 70 days). Therefore, when the LCA dosage was calculated per g body weight, the livers of newborns were exposed to larger amounts of LCA. The dosage was then given per liver/body weight ratio for an accurate comparison with adults. Bile flow was reduced by 7-18% in newborns, while a maximum decrease of 90% was recorded in adults by 2 h post injection, the latter drop in bile flow being proportional to LCA retention in the liver. In contrast, LCA retention was minimal in young rats with 91-95% of it being excreted via the bile. The decreased susceptibility of newborns to cholestasis appears to be related to their capacity to excrete LCA.