Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Krones, E; Eller, K; Pollheimer, MJ; Racedo, S; Kirsch, AH; Frauscher, B; Wahlström, A; Ståhlman, M; Trauner, M; Grahammer, F; Huber, TB; Wagner, K; Rosenkranz, AR; Marschall, HU; Fickert, P.
NorUrsodeoxycholic acid ameliorates cholemic nephropathy in bile duct ligated mice.
J Hepatol. 2017; 67(1):110-119
Doi: 10.1016/j.jhep.2017.02.019
Web of Science
PubMed
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FullText_MUG
- Führende Autor*innen der Med Uni Graz
- Fickert Peter
- Tatscher Elisabeth
- Co-Autor*innen der Med Uni Graz
- Eller Kathrin
- Frauscher Bianca
- Kirsch Alexander
- Pollheimer Marion
- Racedo Silvia Maria
- Rosenkranz Alexander
- Trauner Michael
- Wagner Karin
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- Abstract:
- BACKGROUND & AIMS: Severe cholestasis may cause cholemic nephropathy that can be modeled in common bile duct ligated (CBDL) mice. We aimed to explore the therapeutic efficacy and mechanisms of norursodeoxycholic acid (norUDCA) in cholemic nephropathy. METHODS: In 8-week CBDL mice fed with norUDCA (prior or post CBDL) or chow we evaluated serum urea levels, urine cytology and urinary neutrophil gelatinase associated lipocalin (uNGAL), kidney and liver tissue quantification of fibrosis by hydroxyproline content and gene chip expression looking at key genes of inflammation and fibrosis. Moreover, we comprehensively analysed bile acid profiles in liver, kidney, serum and urine samples. RESULTS: NorUDCA-fed CBDL mice had significantly lower serum urea and uNGAL levels and less severe cholemic nephropathy as demonstrated by normal urine cytology, significantly reduced tubulointerstitial nephritis, and renal fibrosis as compared to controls. NorUDCA underwent extensive metabolism to produce even more hydrophilic compounds that were significantly enriched in kidneys. CONCLUSION: NorUDCA ameliorates cholemic nephropathy due to the formation of highly hydrophilic metabolites enriched in kidney. Consequently, norUDCA may represent a medical treatment for cholemic nephropathy. LAY SUMMARY: The term cholemic nephropathy describes renal dysfunction together with characteristic morphological alterations of the kidney in obstructive cholestasis that can be mimicked by ligation of the common bile duct in mice. Feeding the hydrophilic bile acid norUDCA to bile duct ligated mice leads to a significant amelioration of the renal phenotype due to the formation of highly hydrophilic metabolites enriched in the kidney and may therefore represent a medical treatment for cholemic nephropathy.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals - administration & dosage
- Bile Acids and Salts - urine
- Cholestasis - complications
- Disease Models, Animal - administration & dosage
- Fibrosis - administration & dosage
- Kidney - drug effects, metabolism, pathology
- Kidney Diseases - drug therapy
- Ligation - administration & dosage
- Lipocalin-2 - blood
- Male - administration & dosage
- Mice - administration & dosage
- Mice, Inbred C57BL - administration & dosage
- Nephritis, Interstitial - drug therapy
- Ursodeoxycholic Acid - analogs & derivatives, metabolism, therapeutic use
- Find related publications in this database (Keywords)
- Acute kidney injury
- Bile acids
- Bile acid therapy
- Bile cast nephropathy
- Kidney fibrosis
- Liver cirrhosis
- Renal failure