Effect of bile acid hydroxylation on biliary protoporphyrin excretion in rat liver.
The relationships between bile acid structure, protoporphyrin load, and biliary protoporphyrin excretion were studied in rat livers perfused with 0 or 0.7 mumol/min taurocholate and protoporphyrin loads between 350 and 35,525 nmol. Bile acid treatment increased the excretion of extracted protoporphyrin from 0.4 to 28%, the maximal biliary protoporphyrin concentration 32-fold, the protoporphyrin excretion rate approximately 150-fold, and the coupling of excreted protoporphyrin to bile acid. Infusions (0.7 mumol/min) of bile acids differing in structure with 1,500 nmol protoporphyrin all significantly increased protoporphyrin excretion but ursodeoxycholate and tauroursodeoxycholate did so less than others. Infusions (0.175-1.4 mumol/min) of taurocholate, deoxycholate, ursodeoxycholate, and chenodeoxycholate confirmed that protoporphyrin excretion increased significantly more with taurocholate or deoxycholate than chenodeoxycholate and chenodeoxycholate more than ursodeoxycholate. The relative ineffectiveness of dihydroxylated bile acids with a hydroxy group at the seven position (alpha- or beta-configuration) was not correlated with physicochemical parameters of the bile acids and remains unexplained. The findings suggest that ursodeoxycholate is the least acceptable bile acid to consider as a potential treatment for protoporphyria.
Berenson
M M
MM
Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City 84132.
Garcia Marin
J J
JJ
Gunther
C
C
D000818:Animals; D001646:Bile / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000494:pharmacology*; D006900:Hydroxylation; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; 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