1975
DOI: 10.1042/bj1460285
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Stimulation of the pathway of porphyrin synthesis in the liver of rats and mice by griseofulvin, 3,5-Diethoxycarbonyl-1,4-dihydrocollidine and related drugs: evidence for two basically different mechanisms

Abstract: Griseofulvin and isogriseofulvin cause, like 3,5-diethoxycarbonyl-1,4-dihydrocollidine, a fall in the activity of the hepatic enzyme porphyrin-metal chelatase and accumulation of protoporphyrin in the liver. Analogues of either griseofulvin or 3,5-diethoxycarbonyl-1,4-dihydrocollidine which do not decrease the chelatase activity are not porphyrogenic on their own, but can potentiate the porphyria caused by 3,5-diethoxycarbonyl-1,4-dihydrocollidine. This suggests the existence of two basically different mechani… Show more

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Cited by 52 publications
(26 citation statements)
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References 16 publications
(22 reference statements)
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“…DDC, EDDC and griseofulvin cause hepatic porphyrias in mice by markedly inhibiting ferrochelatase activity in the liver (De Matteis et al 1973, 1981De Matteis and Gibbs 1975). The present work has confirmed that the hepatic p0rphyrias produced by these agents can be modelled in vitro, as addition of these chemicals to primary cultures of mouse hepatocytes resulted in a rapid and sustained inhibition of ferrochelatase activity and accumulation of porphyrins.…”
Section: Discussionsupporting
confidence: 88%
See 1 more Smart Citation
“…DDC, EDDC and griseofulvin cause hepatic porphyrias in mice by markedly inhibiting ferrochelatase activity in the liver (De Matteis et al 1973, 1981De Matteis and Gibbs 1975). The present work has confirmed that the hepatic p0rphyrias produced by these agents can be modelled in vitro, as addition of these chemicals to primary cultures of mouse hepatocytes resulted in a rapid and sustained inhibition of ferrochelatase activity and accumulation of porphyrins.…”
Section: Discussionsupporting
confidence: 88%
“…In contrast, our studies have confirmed that ferrochelatase activity is inhibited in mouse hepatocytes exposed to griseofulvin, but the onset of this inhibition is much slower than observed with the dihydropyridines. This explains why it was not observed previously in isolated mouse hepatocytes where the incubation period was just 4 h. It is noteworthy that similar differences in the rate of onset of porphyria have been noted in in vivo studies in mice fed griseofulvin or dihydropyridines (De Matteis et al 1973;De Matteis and Gibbs 1975).…”
Section: Discussionmentioning
confidence: 51%
“…Hepatic ferrochelatase activities would be expected to be decreased by Ͼ90% in both Fech mice and those treated with griseofulvin for 3 weeks. 9,54,55 Despite equivalent levels of hepatic protoporphyrin and cholestatic injury in the two models there was a marked stimulation of cytochrome P450 isoforms, Hmox1 and Alas1 expression after drug treatment that was not seen in the mutant mouse ( Figure 7). 17,38 This induction of Alas1 and Hmox1 was much greater than the modest change observed with the phenobarbital-like CAR agonist TCPOBOP.…”
Section: Comparison With Griseofulvin Protoporphyriamentioning
confidence: 99%
“…Both genetic (fech/fech mice 9 ) and chemically-induced (i.e., by griseofulvin 10 ) animal models of EPP are available. The antifungal drug griseofulvin, used for the treatment of dermatomycosis for more than 30 years, 11 generates N-methyl-protoporphyrin in liver cells, 12,13 which inhibits ferrochelatase activity.…”
mentioning
confidence: 99%