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Biochem J. 1991 December 15; 280(Pt 3): 813–816. | PMCID: PMC1130528 |
Labelling in vivo and chirality of griseofulvin-derived N-alkylated protoporphyrins. F De Matteis, A H Gibbs, S R Martin, and R L Milek MRC Toxicology Unit, MRC Laboratories, Carshalton, Surrey, U.K. Abstract 1. We have compared the response to griseofulvin of rats and mice and, in mice, the effect of griseofulvin itself with that of two of its analogues. The severity of protoporphyria shows a correlation with the accumulation of both types of N-alkylated porphyrins previously described after treatment with this drug, namely N-methylproptoporphyrin and the N-griseofulvin protoporphyrin adduct. 2. Both N-alkylporphyrins are chiral, are labelled from 5-amino[4-14C]laevulinate, and their liver accumulation can be inhibited by pretreatment with a suicide substrate of cytochrome P-450, which also prevents porphyria. 3. These findings suggest that cytochrome P-450 is involved in the mechanism of griseofulvin-induced protoporphyria by generating N-methylprotoporphyrin. The N-griseofulvin protoporphyrin adduct may also originate from cytochrome P-450, but more work is necessary to elucidate whether it acts as the precursor for N-methylprotoporphyrin. Full text Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (671K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References. These references are in PubMed. This may not be the complete list of references from this article. - DE MATTEIS F, RIMINGTON C. Disturbance of porphyrin metabolism caused by griseofulvin in mice. Br J Dermatol. 1963 Mar;75:91–104. [PubMed]
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