Experimental murine protoporphyria induced by griseofulvin (GF): the relationship between hepatic porphyrin levels and liver function test values in mice treated with GF.
To investigate the hepatic abnormalities accompanying experimental protoporphyria due to griseofulvin (GF), liver function test values and porphyrin levels in mice were assayed at days 2, 4, 8, and 16 after starting the administration of 0.5% GF feed. Furthermore, in an attempt to elucidate the harmful effects of GF on liver functions, the above mentioned assay was also performed after the feed was discontinued in mice given 0.5% GF feed for 16 days. The hepatic protoporphyrin (PP) level had already risen by day 2, but the erythrocytic PP level was within normal limits at that time. Hepatic PP levels increased gradually, followed by an increase in erythrocytic PP levels. The variation in liver function test values roughly paralleled the porphyrin levels. Over the time span of the response to GF, the variations in the serum glutamate oxaloacetate transaminase (S-GOT) levels, serum glutamate pyruvate transaminase (S-GPT) levels, and leucine amino peptidase (LAP) levels resembled those in hepatic PP. On the other hand, the changes in alkaline phosphatase (ALP) levels paralleled those of the erythrocytic PP levels. Erythrocytic and fecal protoporphyrin levels decreased to the normal level one month after the discontinuation of GF administration, but the hepatic protoporphyrin level still was 53.6 times higher than the normal level two months after switching to normal feed. The values of liver function tests had returned to within the normal range after one month. By the fourth day after the administration of GF, a brown pigmented material could be observed around the hepatocytes and the Glisson sheath; the amount of this material increased day by day.(ABSTRACT TRUNCATED AT 250 WORDS)
Tanaka
K
K
Department of Dermatology, Nagasaki University School of Medicine, Japan.
Ohgami
T
T
Nonaka
S
S
D000818:Animals; D004912:Erythrocytes / Q000378:metabolism; D005243:Feces / Q000737:chemistry; D006118:Griseofulvin; D008099:Liver / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011164:Porphyrias / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D011524:Protoporphyrins / Q000378:metabolism*
D011524:Protoporphyrins; D006118:Griseofulvin