Chenodeoxycholic Acid Induced Liver Injury in Pregnant and Neonatal Baboons

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Abstract
The prolonged feeding of chenodeoxycholic acid produces hepatic injury in both pregnant and non-pregnant baboons. CDC feeding does not adversely affect ovarina function and no teratogenic effects of this bile acid were noted in 16 live birth and two stillborn progeny of CDC fed animals. However, 10 of the 16 live birth neonates and one stillborn had focal hepatic lesions histologically similar to those observed in the adult animals. In addition one neonate had gross hepatic necrosis. The severity of the liver damage was related to the content of lithocholic acid in the bile of both the neonates and their mothers. Experiments with 14C-chenodeoxycholic and 14C-lithocholic acid demonstrate that the lithocholate in the enterohepatic circulation of the neonate is derived from the CDC fed to the pregnant adult. In the gallbladder bile of the neonate most, but not all, of the lithocholate is conjugated but unsulfated. Both newborn and adult baboons sulfate lithocholic acid but to an extent less than that reported for man. Less efficient sulfation of lithocholic acid in the baboon may exaggerate the toxicity of CDC feeding in this species compared to man. Nevertheless, the potential for adverse effects on the fetal liver must be recognized as a risk associated with the use of chenodeoxycholic acid in women of child-bearing age.