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SHR Neuro Krebs Kardio Lipid

Zollner, G; Marschall, HU; Wagner, M; Trauner, M.
Role of nuclear receptors in the adaptive response to bile acids and cholestasis: pathogenetic and therapeutic considerations.
Mol Pharm. 2006; 3(3): 231-251.
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Autor/innen der Med Uni Graz:
Trauner Michael
Wagner Martin
Zollner Gernot
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Abstract:
Cholestasis results in intrahepatic accumulation of cytotoxic bile acids which cause liver injury ultimately leading to biliary fibrosis and cirrhosis. Cholestatic liver damage is counteracted by a variety of intrinsic hepatoprotective mechanisms. Such defense mechanisms include repression of hepatic bile acid uptake and de novo bile acid synthesis. Furthermore, phase I and II bile acid detoxification is induced rendering bile acids more hydrophilic. In addition to "orthograde" export via canalicular export systems, these compounds are also excreted via basolateral "alternative" export systems into the systemic circulation followed by renal elimination. Passive glomerular filtration of hydrophilic bile acids, active renal tubular secretion, and repression of tubular bile acid reabsorption facilitate renal bile acid elimination during cholestasis. The underlying molecular mechanisms are mediated mainly at a transcriptional level via a complex network involving nuclear receptors and other transcription factors. So far, the farnesoid X receptor FXR, pregnane X receptor PXR, and vitamin D receptor VDR have been identified as nuclear receptors for bile acids. However, the intrinsic adaptive response to bile acids cannot fully prevent liver injury in cholestasis. Therefore, additional therapeutic strategies such as targeted activation of nuclear receptors are needed to enhance the hepatic defense against toxic bile acids.
Find related publications in this database (using NLM MeSH Indexing)
Adaptation, Biological - physiology
Animals -
Bile Acids and Salts - metabolism Bile Acids and Salts - secretion
Bile Ducts, Intrahepatic - metabolism Bile Ducts, Intrahepatic - secretion
Biological Transport, Active - physiology
Cholestasis - etiology Cholestasis - therapy
Enterohepatic Circulation - physiology
Humans -
Hydroxylation -
Kidney - blood supply Kidney - metabolism
Metabolic Detoxication, Phase II -
Models, Biological -
Receptors, Cytoplasmic and Nuclear - metabolism

Find related publications in this database (Keywords)
bile acid transport
bile acid detoxification
bile acid synthesis
transcription factors
nuclear (orphan) receptors
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