Protoporphyrin hepatopathy. Effects of cholic acid ingestion in murine griseofulvin-induced protoporphyria.

Abstract

A B S T R A C T 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 < 0.0001), erythrocytes (P < 0.05), and plasma (P < 0.05), and higher for feces (P < 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 < 0.05.These data suggest that in selected circumstances, Drs. Sklar and Goldsman participated in these studies during student research elective periods at Columbia University College of Physicians and Surgeons. Address all correspondence to Dr. Poh-Fitzpatrick.

Inhibited Lipid Peroxidation in Griseofulvin-Induced Experimental Protoporphyria.

“…Griseofulvin (GF), an antibiotic used for treatment of fungal infections, is known to induce hepatic protoporphyria in mice [7,8] by inhibiting FC [9]. Although murine G F-induced porphyria is mainly a hepatic and not an erythropoietic disorder, it has served as a model for studies of several aspects of human EPP [10]. We used this model for measurement of the formation of lipid peroxides and the concentration of iron in the liver in order to elucidate their role in the pathogenesis of hepatocellular injury caused by PP.…”

“…Since PP is the major hepatic porphyrin deposited in this condition, total porphyrin levels were expressed as PP, but a coproporphyrin I standard was preferred, because of its greater stability. Finally, a recalculation for conversion to PP content was performed according to Poh-Fitzpatrick et al [10].…”