Effects of the fungicide prochloraz on xenobiotic metabolism in rainbow trout: inhibition in vitro and time course of induction in vivo.
1. Interactions between the fungicide prochloraz and the hepatic cytochrome P-450 of rainbow trout were studied by determination of enzymic activities in vitro using the microsomal fraction, and by kinetic studies. 2. Prochloraz inhibited 7-ethoxyresorufin-O-deethylase (EROD) in vitro. This inhibition was partially non-competitive: the enzyme-substrate-inhibitor (ESI) complex was catalytically active (68% of the activity of the enzyme-substrate complex). 3. Prochloraz in vitro inhibited aldrin epoxidase (AE) by a linear mixed-type mechanism. This inhibition might be high because of high affinity for prochloraz and lack of catalytic activity of the ESI complex. 4. Effects of prochloraz in vivo were studied as a function of time after intraperitoneal injection. Total cytochrome P-450 increased for more than 21 days. 5. EROD increased slightly at day 4 and then returned to control level. Kinetics showed an increase in apparent Km and Vmax. AE was strongly inhibited at day 4 (large increase in apparent Km) and then returned to control level in 21 days. 6. Spectral interactions with aniline showed strong inhibition and recovery to an activated level at day 21.
Snegaroff
J
J
Laboratoire de Phytopharmacie, INRA, Versailles, France.
Bach
J
J
D000818:Animals; D019363:Cytochrome P-450 CYP1A1; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005659:Fungicides, Industrial / Q000494:pharmacology*; D014453:Glucuronosyltransferase / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology*; D007700:Kinetics; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D012487:Salmonidae / Q000378:metabolism*; D014337:Trout / Q000378:metabolism*
D065607:Cytochrome P-450 Enzyme Inhibitors; D005659:Fungicides, Industrial; D007093:Imidazoles; D003577:Cytochrome P-450 Enzyme System; C045362:prochloraz; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; C019647:aldrin epoxidase; D019363:Cytochrome P-450 CYP1A1; D014453:Glucuronosyltransferase