Protoporphyrin hepatopathy. Effects of cholic acid ingestion in murine griseofulvin-induced protoporphyria.
Short-term effects of cholic acid ingestion on hepatic accumulation, fecal excretion, and blood levels of protoporphyrin were studied in vivo in griseofulvin-induced protoporphyric mice. Experimental mice that received feed with 2% griseofulvin and 0.5% cholic acid were compared with control mice that received feed with 2% griseofulvin for 4 wk. Five mice from each group were assessed each week for liver and blood porphyrin levels. Fecal protoporphyrin was compared weekly in the total pooled output of each population. Mean protoporphyrin levels were significantly lower for liver (P less than 0.0001), erythrocytes (P less than 0.05), and plasma (P less than 0.05), and higher for feces (P less than 0.001) for the mice that were fed cholic acid. Microscopic protoporphyrin deposits, inflammation, necrosis, and dysplasia were more severe in livers of control mice. A second experimental design compared four regimens in the feed given to all mice after 1-wk induction with 2% griseofulvin: (a) 0.5% cholic acid, (b) no adulterant, (c) 2% griseofulvin and 0.5% cholic acid, and (d) 2% griseofulvin. No difference in protoporphyrin removal from livers of mice in groups 1 and 2 was observed after 1 and 2 wk of these regimens. The apparent reduction in hepatic protoporphyrin content in mice of group 3 as compared with group 4 at weeks 2 and 3 was not significant at P less than 0.05. These data suggest that in selected circumstances, hepatic protoporphyrin secretion may be enhanced in protoporphyric disease states by bile salt supplementation.
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D002793:Cholic Acids / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005243:Feces / Q000032:analysis; D005260:Female; D006118:Griseofulvin / Q000008:administration & dosage / Q000097:blood; D006801:Humans; D008099:Liver / Q000032:analysis / Q000648:ultrastructure; D008107:Liver Diseases / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D011164:Porphyrias / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D011166:Porphyrins / Q000378:metabolism*; D011524:Protoporphyrins / Q000097:blood / Q000378:metabolism*
D002793:Cholic Acids; D011166:Porphyrins; D011524:Protoporphyrins; D006118:Griseofulvin