Fxr−/− mice adapt to biliary obstruction by enhanced phase I detoxification and renal elimination of bile acids
作者： Hanns-Ulrich Marschall , Martin Wagner , Karl Bodin , Gernot Zollner , Peter Fickert
DOI: 10.1194/JLR.M500427-JLR200
关键词:
摘要: Farnesoid X receptor knockout (Fxr−/−) mice cannot upregulate the bile salt export pump in acid loading or cholestatic conditions. To investigate whether Fxr−/− differ detoxification compared with wild-type mice, we performed a comprehensive analysis of acids extracted from liver, bile, serum, and urine naive common duct-ligated using electrospray gas chromatography mass spectrometry. In addition, hepatic renal gene expression levels Cyp2b10 Cyp3a11, protein putative acid-transporting proteins, were investigated. We found significantly enhanced hydroxylation particular hydroxylations cholic 1β, 2β, 4β, 6α, 6β, 22, 23 position excretion these metabolites urine. The level Cyp3a11 was increased liver whereas multidrug resistance-related 4 (Mrp4) kidneys both genotypes during duct ligation. conclusion, detoxify accumulating by reactions probably catalyzed Cyp3a11. formed excreted into urine, most likely participation Mrp4.
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