BACKGROUND: Unconjugated hyperbilirubinemia, a feature of neonatal jaundice or Crigler-Najjar syndrome, can lead to neurotoxicity and even death. We previously demonstrated that unconjugated bilirubin (UCB) can be eliminated via transintestinal excretion in Gunn rats, a model of unconjugated hyperbilirubinemia, and that this is stimulated by enhancing fecal fatty acid excretion. Since transintestinal excretion also occurs for cholesterol (TICE), we hypothesized that increasing fecal cholesterol excretion and/or TICE could also enhance fecal UCB disposal and subsequently lower plasma UCB concentrations. METHODS: To determine whether increasing fecal cholesterol excretion could ameliorate unconjugated hyperbilirubinemia, we treated hyperbilirubinemic Gunn rats with ezetimibe (EZE), an intestinal cholesterol absorption inhibitor, and/or a liver X receptor (LXR) and farnesoid X receptor (FXR) agonist (T0901317 (T09) and obeticholic acid (OCA), respectively), known to stimulate TICE. RESULTS: We found that EZE treatment alone or in combination with T09 or OCA increased fecal cholesterol disposal but did not lower plasma UCB levels. CONCLUSIONS: These findings do not support a link between the regulation of transintestinal excretion of cholesterol and bilirubin. Furthermore, induction of fecal cholesterol excretion is not a potential therapy for unconjugated hyperbilirubinemia. IMPACT: Increasing fecal cholesterol excretion is not effective to treat unconjugated hyperbilirubinemia. This is the first time a potential relation between transintestinal excretion of cholesterol and unconjugated bilirubin is investigated. Transintestinal excretion of cholesterol and unconjugated bilirubin do not seem to be quantitatively linked. Unlike intestinal fatty acids, cholesterol cannot "capture" unconjugated bilirubin to increase its excretion. These results add to our understanding of ways to improve and factors regulating unconjugated bilirubin disposal in hyperbilirubinemic conditions.
- MeSH
- bilirubin chemie MeSH
- cholesterol metabolismus MeSH
- Criglerův-Najjarův syndrom metabolismus terapie MeSH
- dietní tuky farmakokinetika MeSH
- ezetimib farmakologie terapeutické užití MeSH
- feces chemie MeSH
- fluorované uhlovodíky farmakologie terapeutické užití MeSH
- haptoglobiny analýza MeSH
- hyperbilirubinemie terapie MeSH
- jaterní receptor X metabolismus MeSH
- krysa rodu rattus MeSH
- kyselina chenodeoxycholová analogy a deriváty farmakologie terapeutické užití MeSH
- lipidy krev MeSH
- náhodné rozdělení MeSH
- potkani Gunn MeSH
- PPAR delta metabolismus MeSH
- receptory cytoplazmatické a nukleární metabolismus MeSH
- střeva účinky léků metabolismus MeSH
- sulfonamidy farmakologie terapeutické užití MeSH
- žluč chemie MeSH
- žlučové kyseliny a soli metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- bilirubin metabolismus MeSH
- cholelitiáza diagnóza etiologie terapie MeSH
- Criglerův-Najjarův syndrom metabolismus terapie MeSH
- experimenty na zvířatech MeSH
- hladovění metabolismus MeSH
- hyperbilirubinemie etiologie metabolismus MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- novorozenecká hyperbilirubinemie etiologie metabolismus MeSH
- primární prevence MeSH
- probiotika metabolismus terapeutické užití MeSH
- sloučeniny zinku metabolismus MeSH
- střeva metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- zvířata MeSH
- MeSH
- bilirubin chemie metabolismus škodlivé účinky MeSH
- Criglerův-Najjarův syndrom metabolismus MeSH
- enterohepatická cirkulace MeSH
- finanční podpora výzkumu jako téma MeSH
- hyperbilirubinemie metabolismus MeSH
- lidé MeSH
- novorozenecká žloutenka metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
