Effects of phenobarbital upon bile acid synthesis in two strains of rats.
Rats of the Wistar and Sprague-Dawley strains were injected with sodium phenobarbital (100 mg/kg body wt/day) for 8 days. Fecal bile acid excretion was measured on days 6 and 8 of the experiment, and biliary bile acid composition, hepatic microsomal cholesterol, 7alpha-hydroxylase, and 7alpha-hydroxy-4-cholesten-3-one 12alpha-hydroxylase were determined at the end of the study. In the Wistar rat, injection of phenobarbital produced a doubling of fecal bile acid output (controls, 5.3 mg/rat/day; treated rats, 10.6 mg/rat/day) and a two-threefold increase in cholesterol 7alpha-hydroxylase. The fecal bile acid output of Sprague-Dawley rats increased 20% in response to phenobarbital (controls, 9,5 mg/rat/day; treated rats, 11.6 mg/rat/day). The activity of cholesterol 7alpha-hydroxylase remained unchanged. In both strains, phenobarbital treatment produced a decrease in the proportion of cholic acid in total bilary bile acids (controls, 85%; treated groups, 65%). This was associated with a decrease of 7alpha-hydroxy-4-cholesten-3-one 12alpha-hydroxylase activity by ca. 50%. Biliary cholesterol concentrations were reduced in phenobarbital treated rats of both strains, but liver cholesterol concentrations remained unchanged. The drug produced a 25% increase in liver wt, on the average.
D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000096:biosynthesis*; D002784:Cholesterol; D002793:Cholic Acids / Q000096:biosynthesis; D005243:Feces / Q000032:analysis; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D013045:Species Specificity; D013250:Steroid Hydroxylases / Q000378:metabolism; D013997:Time Factors
D001647:Bile Acids and Salts; D002793:Cholic Acids; D002784:Cholesterol; D013250:Steroid Hydroxylases; D010634:Phenobarbital