Studies on Increased Bile Formation Produced by Polyoxybenzenes in Rats

Abstract

Mechanism of hypercholeretic effect of 3 polyoxybenzenes, 2,4,6-trihydroxypropiophenone (THPP), 4-methylumbelliferone (4-MU) and 3-(2'',4'',5''-triethoxybenzoyl)propionic acid (AA-149), was studied in rats. Biliary clearance of 14C-labeled erythritol indicated that all the choleretics increased canalicular bile production. AA-149 excreted in the bile chiefly as the glucuronide provided no significant osmotic drive for bile formation. Both the biliary bile acid concentration and total biliary excretion of bile acids were lower in the rats treated with THPP, 4-MU or AA-149 than in control rats. These choleretics were also effective in the isolated rat liver perfusion system, in which concentration and output of biliary bile acids were low. Thus, it was unlikely that bile acids were involved in the hypercholeresis induced by the choleretics. THPP, 4-MU and AA-149 increased biliary excretion of Na both in the biliary-cannulated rats and in the isolated rat liver perfusion system. The hypercholeresis induced by THPP, 4-MU and AA-149 appears to be due to an enhanced formation of the bile acid-independent fraction of canalicular origin, probably mediated by the active transfer of Na into the canaliculi.