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Iepatic vitamin D 25‐hydroxylase: Inhibition by bile duct ligation or bile salts
Author(s) -
Bolt Erry J. G.,
Sitrin Michael D.,
Favus Murray J.,
Rosenberg Irwin H.
Publication year - 1981
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840010512
Subject(s) - cholestasis , medicine , endocrinology , bile duct , hydroxylation , bile acid , biliary atresia , vitamin d and neurology , vitamin , chemistry , enzyme , biochemistry , liver transplantation , transplantation
Bone disease and low serum levels of 25‐hydroxyvitamin D are prevalent in cholestatic syndromes such as primary biliary cirrhosis and biliary atresia. Defective hydroxylation, along with malabsorption of vitamin D, could be a factor in 25‐hydroxyvitamin D depletion. To assess hepatic hydroxylation during experimental cholestasis, we studied vitamin D 25‐hydroxylase activity in liver homogenates of rats after 7, 14, and 21 days of bile duct ligation. We have also studied the effects of bile acids on this enzyme in vitro. Hepatic 25‐hydroxylation was depressed after 7 days ligation in only 1 of 4 animals, but by 14 days, all animals showed a marked reduction with a mean decrease of 64% in specific activity. Total liver enzyme activity was reduced by 43% at 14 days. In the ligated animals, liver histology showed progressive bile stasis, focal necrosis, bile ductular proliferation, periductular and periportal inflammation, and fibrosis. Addition of bile acids to the in vitro assay in concentrations approximating those found in cholestasis produced marked inhibition of vitamin D 25‐hydroxylase activity.