In vitro metabolism of pyrethroid pesticides by rat and human hepatic microsomes and cytochrome p450 isoforms.
Article Details
- CitationCopy to clipboard
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
Drug Enzyme Kind Organism Pharmacological Action Actions Bioallethrin Cytochrome P450 1A1 Protein Rat NoSubstrateDetails Bioallethrin Cytochrome P450 2A1 Protein Rat NoSubstrateDetails Bioallethrin Cytochrome P450 2C11 Protein Rat NoSubstrateDetails Bioallethrin Cytochrome P450 2C19 Protein Humans NoSubstrateDetails Bioallethrin Cytochrome P450 2C6 Protein Rat NoSubstrateDetails Bioallethrin Cytochrome P450 2C8 Protein Humans NoSubstrateDetails Bioallethrin Cytochrome P450 2C9 Protein Humans NoSubstrateDetails Bioallethrin Cytochrome P450 3A1 Protein Rat NoSubstrateDetails Bioallethrin Cytochrome P450 3A2 Protein Rat NoSubstrateDetails Bioallethrin Cytochrome P450 3A4 Protein Humans NoSubstrateDetails