NorUrsodeoxycholic acid ameliorates cholemic nephropathy in bile duct ligated mice
Standard
NorUrsodeoxycholic acid ameliorates cholemic nephropathy in bile duct ligated mice. / Krones, Elisabeth; Eller, Kathrin; Pollheimer, Marion J; Racedo, Silvia; Kirsch, Alexander H; Frauscher, Bianca; Wahlström, Annika; Ståhlman, Marcus; Trauner, Michael; Grahammer, Florian; Huber, Tobias B; Wagner, Karin; Rosenkranz, Alexander R; Marschall, Hanns-Ulrich; Fickert, Peter.
In: J HEPATOL, Vol. 67, No. 1, 07.2017, p. 110-119.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - NorUrsodeoxycholic acid ameliorates cholemic nephropathy in bile duct ligated mice
AU - Krones, Elisabeth
AU - Eller, Kathrin
AU - Pollheimer, Marion J
AU - Racedo, Silvia
AU - Kirsch, Alexander H
AU - Frauscher, Bianca
AU - Wahlström, Annika
AU - Ståhlman, Marcus
AU - Trauner, Michael
AU - Grahammer, Florian
AU - Huber, Tobias B
AU - Wagner, Karin
AU - Rosenkranz, Alexander R
AU - Marschall, Hanns-Ulrich
AU - Fickert, Peter
N1 - Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
PY - 2017/7
Y1 - 2017/7
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.1016/j.jhep.2017.02.019
DO - 10.1016/j.jhep.2017.02.019
M3 - SCORING: Journal article
C2 - 28242240
VL - 67
SP - 110
EP - 119
JO - J HEPATOL
JF - J HEPATOL
SN - 0168-8278
IS - 1
ER -
