ALTERATIONS OF PORPHYRIN METABOLISM IN MICE BY GRISEOFULVIN

Human erythropoietic protoporphyria (EPP) is an inherited disorder of porphyrin metabolism due to defective ferrochelatase. Griseofulvin (Gf) is believed to selectively inhibit this enzyme but is also known to precipitate acute attacks in patients with acute intermittent porphyria. Faecal coproporphyrin III (CP) and protoporphyrin (PP) in samples collected from mice treated for 1-7 days with oral 2.5% griseofulvin (Gf) in their diet were progressively increased compared with controls. A 2-fold and 4-fold increase in CP and PP, respectively, was seen after one day of feeding. After seven days the increases were 40-100-fold, respectively. Urinary ALA and PBG were, respectively, increased 20 and 2-fold. Mice fed with Gf for 3 days, enhanced the production of uroporphyrins I and III (10-fold increase), and heptacarboxylporphyrin. Mice fed Gf for 3 days and simultaneously injected with Haem-arginate (10 μg daily for 3 days), had normal coproporphyrin-lll, ALA and PBG-levels. The protoporphyrin-IX level was, however, only marginally reduced.  The present study indicates that griseofulvin might be inhibiting protoporphyrinogen oxidase (PPOX) activity in addition to ferrochelatase (FC) simulating variegate porphyria (VP) and thus precipitating porphyric attacks in susceptible individuals.