Effect of bile acids on hepatic protoporphyrin metabolism in perfused rat liver.
To determine the effect of bile acids on hepatic protoporphyrin metabolism, balance studies were performed in isolated perfused rat livers. Hepatic protoporphyrin metabolism was found to increase linearly as a function of protoporphyrin dose in livers infused with and without taurocholate (0.7 mumol/min), but their rates differed significantly. Employing a standard 1500-nmol protoporphyrin bolus dose, infusions (0.7 mumol/min) of taurocholate, glycocholate, deoxycholate, and chenodeoxycholate, but not tauroursodeoxycholate or ursodeoxycholate, increased protoporphyrin metabolism 1.7- to 2.7-fold over control (0 bile acid) values. Bile acid infusion ranging from 0.175 to 1.4 mumol/min confirmed that both taurocholate and chenodeoxycholate increased protoporphyrin disposal significantly more than ursodeoxycholate. For all bile acids, the increase of protoporphyrin metabolism was most pronounced between biliary bile acid excretion rates of 10-50 nmol/min.g liver. These data indicate that (a) bile acids facilitated protoporphyrin metabolism, (b) bile acid structure influenced the effect, and (c) ursodeoxycholate may not be a prime candidate to study the role of bile acids in the treatment of protoporphyria.
D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D011166:Porphyrins / Q000378:metabolism*; D011524:Protoporphyrins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D001647:Bile Acids and Salts; D011166:Porphyrins; D011524:Protoporphyrins