Induction of fecal cholesterol excretion is not effective for the treatment of hyperbilirubinemia in Gunn rats
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F21%3A10411288" target="_blank" >RIV/00216208:11110/21:10411288 - isvavai.cz</a>
Alternative codes found
RIV/00064165:_____/21:10411288
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=5nOWSM4f9U" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=5nOWSM4f9U</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41390-020-0926-2" target="_blank" >10.1038/s41390-020-0926-2</a>
Alternative languages
Result language
angličtina
Original language name
Induction of fecal cholesterol excretion is not effective for the treatment of hyperbilirubinemia in Gunn rats
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
—
Continuities
V - Vyzkumna aktivita podporovana z jinych verejnych zdroju
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Pediatric Research
ISSN
0031-3998
e-ISSN
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Volume of the periodical
89
Issue of the periodical within the volume
3
Country of publishing house
US - UNITED STATES
Number of pages
8
Pages from-to
510-517
UT code for WoS article
000530593000001
EID of the result in the Scopus database
2-s2.0-85084244306