Hepatobiliary effects of cholic and lithocholic acids: experimental study in hamsters

Etiopathogenesis of biliary atresia remains unknown. Among several theories, one proposes that the disorder may be caused by the toxic effect of monohydroxy bile acids on fetal and neonatal hepatobiliary system. In this paper we evaluated toxic effects produced by ingestion of cholic acid, a trihydroxy bile acid, and lithocholic acid, a monohydroxy bile acid in the hepatobiliary system of a hamster during gestational and perinatal periods. A diet composed by 0.5% cholic acid and 0.25% lithocholic acid was administrated to pregnant hamsters. Liver and bile ducts of the adult and newborn animals were analyzed to point out the changes induced by these acids after birth. Because hamsters and humans have a similar bile metabolism, these animals were eligible for the study. The ingestion of 0.5% lithocholic acid, during hamster's gestation, caused maternal intense ductal/ductular proliferation, inflammatory signs, hepatic cells degeneration and regeneration, hyperplasia of extra hepatic ducts epithelium, and abortion. Both 0.5% cholic acid and 0.25% lithocholic acid ingested by pregnant hamsters, caused ductal/ductular proliferation and hepatobiliary inflammatory damage in a different degree of intensity in adult animals and mild intensity in the young; and also the number of the young was reduced in the litter. We found that the ingestion of these bile acids by hamsters, during gestational period caused different degrees of toxicity on maternal and neonatal hepatobiliary systems. The histopathologic findings observed in biliary atresia patients could not be found in newborn hamsters. New experimental models are needed in the attempt to establish a correlation of these acids with neonatal cholestatic diseases.