2006
DOI: 10.1073/pnas.0604772103
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Benefit of farnesoid X receptor inhibition in obstructive cholestasis

Abstract: The nuclear hormone receptors farnesoid X receptor (FXR) and pregnane X receptor have been implicated in regulating bile acid, lipid, carbohydrate, and xenobiotic metabolism. Bile duct ligation was used to increase endogenous bile acids and evaluate the roles of these receptors in modulating cholestatic liver injury. FXR knockout (KO) mice were found to be protected from obstructive cholestasis. Concurrent deletion of FXR also could ameliorate an increase in liver injury that is seen usually in pregnane X rece… Show more

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Cited by 154 publications
(132 citation statements)
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“…At 2 days after surgery, mortality of the WT mice (16%) was comparable to that of previous reports (for example, Stedman et al 14 ), whereas that of the Shp Ϫ/Ϫ mice was approximately 2-fold higher (33%) ( Table 2). Histologic examination of the livers of Shp Ϫ/Ϫ mice showed extensive areas of bile infarcts, indicating severe liver injury, which were not observed in WT livers ( Fig.…”
Section: Resultssupporting
confidence: 77%
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“…At 2 days after surgery, mortality of the WT mice (16%) was comparable to that of previous reports (for example, Stedman et al 14 ), whereas that of the Shp Ϫ/Ϫ mice was approximately 2-fold higher (33%) ( Table 2). Histologic examination of the livers of Shp Ϫ/Ϫ mice showed extensive areas of bile infarcts, indicating severe liver injury, which were not observed in WT livers ( Fig.…”
Section: Resultssupporting
confidence: 77%
“…12 To further investigate the role of SHP in bile acid homeostasis, we examined the response of C57BL/6 and congenic C57BL/6 Shp Ϫ/Ϫ mice to acute cholestasis induced by ligation of the common bile duct. In contrast to recent results demonstrating relative resistance of Fxr Ϫ/Ϫ mice to bile duct ligation (BDL), 13,14 the Shp Ϫ/Ϫ mice showed increased sensitivity, which was associated with increased bile acid levels and acute liver damage at very early times after BDL.…”
contrasting
confidence: 49%
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“…These compensatory processes provide a suitable window for the treatment of cholestasis. A number of alternative drugs are currently being tested in pre-clinical studies as potential treatments for cholestatic disease, including selective modulators of nuclear receptors and signaling pathways that are thought to mediate cholestasis [8,9] . Resveratrol (3,5,4'-trans-trihydroxystilbene), a polyphenol phytoalexin abundantly found in grape skins and wine, possesses diverse biochemical and physiological actions.…”
Section: Introductionmentioning
confidence: 99%