In vitro metabolism of pyrethroid pesticides by rat and human hepatic microsomes and cytochrome p450 isoforms.

Article Details

Citation

Scollon EJ, Starr JM, Godin SJ, DeVito MJ, Hughes MF

In vitro metabolism of pyrethroid pesticides by rat and human hepatic microsomes and cytochrome p450 isoforms.

Drug Metab Dispos. 2009 Jan;37(1):221-8. doi: 10.1124/dmd.108.022343. Epub 2008 Oct 23.

PubMed ID
18948380 [ View in PubMed
]
Abstract

Species differences in the intrinsic clearance (CL(int)) and the enzymes involved in the metabolism of pyrethroid pesticides were examined in rat and human hepatic microsomes. The pyrethroids bifenthrin, S-bioallethrin, bioresmethrin, beta-cyfluthrin, cypermethrin, cis-permethrin, and trans-permethrin were incubated in rat and human hepatic microsomes in the presence or absence of NADPH. Metabolism was measured using a parent depletion approach. The CL(int) of the pyrethroids was 5- to 15-fold greater in rat relative to human microsomes except for trans-permethrin, which was approximately 45% greater in human microsomes. The metabolism of bifenthrin, S-bioallethrin, and cis-permethrin in rat and human hepatic microsomes was solely the result of oxidative processes. The metabolism of bioresmethrin and cypermethrin in human hepatic microsomes was solely the result of hydrolytic processes. Bioresmethrin and cypermethrin in rat hepatic microsomes and beta-cyfluthrin and trans-permethrin in microsomes from both species were metabolized by both oxidative and hydrolytic pathways. The metabolism of trans-permethrin was reduced when incubated with its diastereomer, cis-permethrin, in both rat and human hepatic microsomes. Rat cytochrome P450 (P450) isoforms that showed activity toward several pyrethroids included CYP1A1, CYP1A2, CYP2C6, CYP2C11, CYP3A1, and CYP3A2. Human P450 isoforms that showed activity toward multiple pyrethroids were CYP2C8, CYP2C9, CYP2C19, and CYP3A4. Species-specific differences in metabolism may result in variable detoxification of pyrethroids, which may in turn result in divergent neurotoxic outcomes. These species differences and isomer interactions in metabolism of pyrethroids should be considered when assessing the potential adverse health effects of pyrethroid pesticides.

DrugBank Data that Cites this Article

Drugs
Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
BioallethrinCytochrome P450 1A1ProteinRat
No
Substrate
Details
BioallethrinCytochrome P450 2A1ProteinRat
No
Substrate
Details
BioallethrinCytochrome P450 2C11ProteinRat
No
Substrate
Details
BioallethrinCytochrome P450 2C19ProteinHumans
No
Substrate
Details
BioallethrinCytochrome P450 2C6ProteinRat
No
Substrate
Details
BioallethrinCytochrome P450 2C8ProteinHumans
No
Substrate
Details
BioallethrinCytochrome P450 2C9ProteinHumans
No
Substrate
Details
BioallethrinCytochrome P450 3A1ProteinRat
No
Substrate
Details
BioallethrinCytochrome P450 3A2ProteinRat
No
Substrate
Details
BioallethrinCytochrome P450 3A4ProteinHumans
No
Substrate
Details