Bile acid sulphotransferase activity in human liver cytosol and the effect of primary biliary cirrhosis and other liver diseases

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Abstract

Objective:

To examine the hypothesis that hepatic bile acid sulphation may be specifically impaired in the cholestatic liver disease, primary biliary cirrhosis (PBC), conceiveably leading to ongoing hepatocyte destruction by retained unconjugated and conjugated hydrophobic bile acids and, conversely, to examine whether sulphation may be induced in PBC to dispose of bile acids retained due to cholestasis.

Methods:

Under optimum substrate conditions and using butanol extraction, hepatic bile acid sulphotransferase (BAST) activity (pmol bile acid sulphate/mg protein/min) was measured by separately incubating six bile acid substrates with liver cytosol from liver biopsy material obtained from 22 patients with PBC, 17 patients with chronic parenchymal liver diseases, 12 of whom had alcoholic liver disease, and nine normal controls.

Results:

Sulphotransferase activity was not age-dependent or sex- or tobacco-related. Bile acid sulphotransferase activity was well preserved in patients with PBC, even in those with cirrhosis, but there appeared to be mild reductions in enzyme activity in those with alcoholic liver disease. In PBC patients, there was a positive correlation between BAST activity and serum bilirubin levels when glycochenodeoxycholic acid (r5=0.473, P<0.05), lithocholic acid (r5=0.504, P<0.05) and taurolithocholic acid (r5=0.443, P<0.05) were used as substrates. There was a good correlation for BAST activities for the different substrates in each PBC patient.

Conclusions:

There was no evidence that primary or secondary reductions in BAST activity contributed to the progression of PBC and it was thought that the reduced enzyme activity in alcoholic liver disease may be due to overall hepatocyte impairment because of the nature of the disease. There is evidence that PBC patients with more severe degrees of cholestasis have increased bile acid sulphation, which could indicate that sulphotransferase enzyme induction occurs in response to cholestasis. Correlation of BAST activities in each patient was indirect evidence that only a single form of the enzyme appears to exist in the human liver.

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