Effect of bile duct ligation on bile acid composition in mouse serum and liver
Youcai Zhang,Ji Young Hong,Cheryl E. Rockwell,Bryan L. Copple,Hartmut Jaeschke,Curtis D. Klaassen +5 more
TLDR
Cholestatic liver diseases can be caused by genetic defects, drug toxicities, hepatobiliary malignancies or obstruction of the biliary tract, and information on which bile acids are actually accumulating during cholestasis is limited.Abstract:
Background
Cholestatic liver diseases can be caused by genetic defects, drug toxicities, hepatobiliary malignancies or obstruction of the biliary tract. Cholestasis leads to accumulation of bile acids (BAs) in hepatocytes. Direct toxicity of BAs is currently the most accepted hypothesis for cholestatic liver injury. However, information on which bile acids are actually accumulating during cholestasis is limited.read more
Citations
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Journal ArticleDOI
Pleiotropic Roles of Bile Acids in Metabolism
TL;DR: This review covers the roles of specific bile acids, synthetic agonists, and their cognate receptors in controlling these diverse functions, as well as their current use in treating human diseases.
Journal ArticleDOI
The ascending pathophysiology of cholestatic liver disease.
Peter L.M. Jansen,Ahmed Ghallab,Nachiket Vartak,Raymond Reif,Frank G. Schaap,Jochen Hampe,Jan G. Hengstler +6 more
TL;DR: It is developed and proposed a new view on the pathophysiology of primary biliary cholangitis and PSC in the hope that these new drugs can be used more effectively, and anti‐inflammatory agents are probably most effective in early disease, while drugs that antagonize BS toxicity may be effective at all disease stages.
Journal ArticleDOI
Circulating Fibroblast Growth Factors as Metabolic Regulators—A Critical Appraisal
TL;DR: This work critically review current data, and proposes that circulating FGF23 is pivotal in the control of phosphate and vitamin D metabolism, and may have additional systemic effects, particularly in chronic kidney disease.
Journal ArticleDOI
Bile acids initiate cholestatic liver injury by triggering a hepatocyte-specific inflammatory response
Shi-Ying Cai,Xinshou Ouyang,Yonglin Chen,Carol J. Soroka,Juxian Wang,Albert Mennone,Yucheng Wang,Wajahat Z. Mehal,Dhanpat Jain,James L. Boyer +9 more
TL;DR: Findings reveal potentially novel mechanisms whereby BAs elicit a hepatocyte-specific cytokine-induced inflammatory liver injury that involves innate immunity and point to likely novel pathways for treating cholestatic liver disease.
Journal ArticleDOI
Novel insight into mechanisms of cholestatic liver injury.
TL;DR: Insight is provided into how these data support recent hypotheses that cholestatic liver injury may not occur through direct bile acid-induced apoptosis, but may involve largely inflammatory cell-mediated liver cell necrosis.
References
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Journal ArticleDOI
Xenobiotic, Bile Acid, and Cholesterol Transporters: Function and Regulation
TL;DR: A comprehensive overview of transporters of the solute carrier family (SLC) is provided with regard to tissue distribution, subcellular localization, and substrate preferences.
Journal ArticleDOI
Bile-acid-induced cell injury and protection
Maria J. Perez,Oscar Briz +1 more
TL;DR: The major beneficial effects of treatment with ursodeoxycholic acid are protection against cytotoxicity due to more toxic BAs; the stimulation of hepatobiliary secretion; antioxidant activity, due in part to an enhancement in glutathione levels; and the inhibition of liver cell apoptosis.
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Toxic bile salts induce rodent hepatocyte apoptosis via direct activation of Fas
William A. Faubion,M. Eugenia Guicciardi,Hideyuki Miyoshi,Steven F. Bronk,Patricia J. Roberts,Phyllis A. Svingen,Scott H. Kaufmann,Gregory J. Gores +7 more
TL;DR: Data suggest that GCDC-induced hepatocyte apoptosis involves ligand-independent oligomerization of Fas, recruitment of FADD, activation of caspase 8, and subsequent activation of effector proteases, including downstream caspases and cathepsin B.
Journal ArticleDOI
The rat canalicular conjugate export pump (Mrp2) is down-regulated in intrahepatic and obstructive cholestasis
Michael Trauner,Marco Arrese,Carol J. Soroka,Meenakshisundaram Ananthanarayanan,Thomas A. Koeppel,Stephan F. Schlosser,Frederick J. Suchy,Dietrich Keppler,James L. Boyer +8 more
TL;DR: Down-regulation of Mrp2 expression may explain impaired biliary excretion of amphiphilic anionic conjugates in these models of cholestasis.
Journal ArticleDOI
Bile Acids Induce Inflammatory Genes in Hepatocytes: A Novel Mechanism of Inflammation during Obstructive Cholestasis
TL;DR: The data demonstrate that Toll-like receptor 4 is not required for the initiation of acute inflammation during cholestasis, and bile acids directly activate a signaling network in hepatocytes that promotes hepatic inflammation during Cholestatic inflammation.