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

Abstract

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.

Discovery of common urinary biomarkers for hepatotoxicity induced by carbon tetrachloride, acetaminophen and methotrexate by mass spectrometry‐based metabolomics

“…Furthermore, accumulation of lithocholic acid has been implicated as a major factor contributing to liver injury because of the inherent cytotoxicity of the hydrophobic bile acids (Deo and Bandiera, ). Additionally, lithocholic acid is thought to participate in the pathogenesis of liver disease and colon cancer (Nagengast et al ., ; Siviero et al ., ).…”

“…This induced hepatotoxicity showed similar effects in patients with cholestatic liver disease (Bremmelgaard and Alme, ) and the animal models of cholestasis (Bossard et al ., ; Wang et al ., ). However, liver toxicity produced by the administration of cholic acid or increases in the level of cholic acid could also be induced by deoxycholic acid, the metabolite of cholic acid, rather than cholic acid itself (Siviero et al ., ). Despite this fact, liver toxicity was more related to cholic acid than deoxycholic acid in this study.…”

Novel high-coverage targeted metabolomics method (SWATHtoMRM) for exploring follicular fluid metabolome alterations in women with recurrent spontaneous abortion undergoing in vitro fertilization

“…Siviero et al . found that cholic acid and lithocholic acid could lead to miscarriage due to inflammation and hepatocyte degeneration 52 .…”

Serum metabolomics using ultra performance liquid chromatography coupled to mass spectrometry in lactating dairy cows following a single dose of sporidesmin

“…In addition, lithocholic acid, a bacterial metabolite of chenodeoxycholate produced in the intestinal tract, has been implicated as a possible hepatotoxin (Miyazaki et al 1984 ). Glycochenodeoxycholic acid is the most toxic known form of chenodeoxycholate, and has also been shown to induce hepatocellular injury in a dose-dependent manner in human patients (Spivey et al 1993 ; Trottier et al 2012 ; Woolbright et al 2015 ; Siviero et al 2008 ).…”