URSO STUDY - A MUST READ

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Nat Clin Pract Gastroenterol Hepatol.

2006 Jun, 3

Drug

Insight: mechanisms and sites of action of ursodeoxycholic

acid in cholestasis.

Beuers U.

U Beuers is a Professor of Medicine in the Department

of Medicine II, Klinikum Grosshadern,

University of Munich, Germany.

Ursodeoxycholic acid (UDCA) exerts anticholestatic effects in various cholestatic

disorders. Several potential mechanisms and sites of action of UDCA have been

unraveled in clinical and experimental studies, which could explain its

beneficial effects. The relative

contribution of these mechanisms to the anticholestatic

action of UDCA depends on the type and stage of the cholestatic

injury. In early-stage primary biliary cirrhosis and primary sclerosing cholangitis,

protection of injured cholangiocytes against the

toxic effects of bile acids might prevail. Stimulation of

impaired hepatocellular secretion by mainly

post-transcriptional mechanisms, including stimulation of synthesis, targeting

and apical membrane insertion of key transporters, seems to be relevant in more

advanced cholestasis. In intrahepatic cholestasis of pregnancy, stimulation of impaired hepatocellular secretion could be crucial for rapid relief

of pruritus and improvement of serum liver tests, as it is in some forms of

drug-induced cholestasis. In cystic fibrosis,

stimulation of cholangiocellular calcium-dependent

secretion of chloride and bicarbonate ions could have a major impact.

Inhibition of bile-acid-induced hepatocyte apoptosis

can have a role in all states of cholestasis that are

characterized by hepatocellular bile-acid retention.

Different mechanisms of action could, therefore, contribute to the beneficial

effect of UDCA under various cholestatic conditions.

PMID: 16741551 [PubMed - in process]

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