Effects of flumethrin on hepatic drug-metabolizing enzymes and antipyrine disposition in rats.
The effects of repeated exposure to the pyrethroid insecticide flumethrin (40 mg/kg intraperitoneally once a day for 6 days) on the activity of cytochrome P450-dependent monooxygenases and UDP-glucuronosyltransferase as well as on antipyrine disposition were investigated in male Wistar rats. Pretreatment with flumethrin decreased the activities of NADPH-cytochrome c reductase (38%), aniline hydroxylase (53%), aminopyrine N-demethylase (54%), and UDP-glucuronosyltransferase (34%), and the content of cytochrome P450 (36%) in hepatic microsomes. Total plasma clearance of antipyrine was decreased by flumethrin pretreatment (54%), while the elimination half-life at beta phase and the mean residence time of antipyrine were increased (96 and 88%, respectively). Urinary excretion of norantipyrine, 4-hydroxyantipyrine, and 3-hydroxymethylantipyrine was decreased by 60, 38, and 33%, respectively, in the 96 hr after flumethrin treatment. In addition, the rate constants for formation of each of these metabolites were decreased by an average of approximately 74%. These findings provide evidence that flumethrin exposure diminishes hepatic enzyme levels and catalytic activities of monooxygenase systems as well as oxidative metabolism of antipyrine.
Anadón
A
A
Department of Toxicology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, Spain.
Martinez-Larrañaga
M R
MR
Diaz
M J
MJ
Bringas
P
P
Fernandez
M C
MC
Martinez
M A
MA
Fernandez-Cruz
M L
ML
D000818:Animals; D000983:Antipyrine / Q000097:blood / Q000378:metabolism* / Q000652:urine; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology*; D011722:Pyrethrins / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
D011722:Pyrethrins; C041392:flumethrin; D003577:Cytochrome P-450 Enzyme System; D000983:Antipyrine