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Biliary secretion and excretion in health and disease: current concepts.
Hofmann, Alan F.
Afiliação
  • Hofmann AF; Division of Gastroenterology. Department of Medicine. University of California, San Diego California 92093-0813, USA. hofmannaf@cs.com
Ann Hepatol ; 6(1): 15-27, 2007.
Article em En | MEDLINE | ID: mdl-17297425
Biliary secretion in health and disease is reviewed. The powerful techniques of molecular biology have enabled cloning of the transporters involved in biliary secretion and the enterohepatic circulation of bile acids. This, in turn has permitted elucidation of their function as well as their regulation by nuclear receptors. Bile acid secretion is required for efficient lipid absorption, and bile acids also possess powerful direct and indirect antimicrobial functions in the small intestine. The enterohepatic circulation results from efficient ileal absorption, and is highly regulated at two sites. In the hepatocyte, biosynthesis of bile acids is regulated in negative feedback manner by the nuclear receptor FXR as well as by cytokines and by a peptide (FGF-19) liberated by bile acids from the ileal enterocyte. In the ileal enterocyte, bile acid reclamation is regulated in negative feedback manner by FXR and other nuclear receptors. The bile salt export pump (BSEP) mediates uphill canalicular bile acid secretion. Inborn defects in its function cause intrahepatic cholestasis in infants; inhibition of its function by drugs causes hepatotoxicity. Bile acid therapy is based on correction of bile acid deficiency by supplemental bile acids or displacement in which a noncytotoxic bile acid (ursodeoxycholic acid, ursodiol, UDCA) is administered and dilutes out the endogenous cytotoxic bile acids. Administration of primary bile acids may be lifesaving in inborn defects of bile acid biosynthesis. A synthetic bile acid, norUDCA is absorbed by the biliary ductules after secretion and cures the peribiliary fibrosis occurring in the MDR2-/- mouse which lacks biliary phospholipid.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Bile / Doenças Biliares Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Ann Hepatol Assunto da revista: GASTROENTEROLOGIA Ano de publicação: 2007 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: México
Buscar no Google
Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Bile / Doenças Biliares Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Ann Hepatol Assunto da revista: GASTROENTEROLOGIA Ano de publicação: 2007 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: México