In vitro effects of an imidazole antifungal, prochloraz, on spectral and catalytic properties of microsomal cytochromes P-450.
1. The imidazole antifungal agent, prochloraz, elicited type II spectral interactions with microsomal cytochromes P-450 from rats pretreated with phenobarbital (PB), 3-methyl-cholanthrene (MC) and dexamethasone (DEX). 2. Prochloraz interacts strongly with type I binding sites of both PB- and DEX-induced cytochromes P-450 and to a lesser extent with cytochromes P-450 from MC-induced rats. 3. The antifungal derivative was a more potent inhibitor of the troleandomycin-nitrosoalkyl-cytochrome P-450 complex formation in DEX-induced microsomes than of the isosafrole-carbene-cytochrome P-450 complex formation in MC-pretreated rats. 4. Prochloraz is a strong inhibitor of the cytochrome P-450-dependent mixed-function oxidases in rat liver microsomal preparations.
Antignac
E
E
Laboratory of Food Toxicology, University of Bordeaux I, Talence, France.
Koch
B
B
Delaforge
M
M
Narbonne
J F
JF
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D005659:Fungicides, Industrial / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D007527:Isoenzymes / Q000096:biosynthesis; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D005659:Fungicides, Industrial; D007093:Imidazoles; D007527:Isoenzymes; D008748:Methylcholanthrene; D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System; C045362:prochloraz; D010634:Phenobarbital