Differential metabolism of O-ethyl O-4-nitrophenyl phenylphosphonothioate by rat and chicken hepatic microsomes.
Lasker-JM; Graham-DG; Abou-Donia-MB
Biochem Pharmacol 1982; 31(11):1961-1967
The metabolism of 0-ethyl-0-4-nitrophenyl-phenylphosphonothioate (EPN) by rat and chicken hepatic microsomes was compared. Liver microsomal preparations were obtained from Leghorn-hens or Sprague- Dawley-rats after induction with sodium-phenobarbital, 3- methylcholanthrene, Arochlor-1254, or EPN. Microsomes were incubated with EPN plus nicotine-adenine-dinucleotide-phosphate (NADPH) or 0-ethyl-0-4-nitrophenyl-phenylphosphonate (EPNO). Reactions were terminated by addition of acetone and residues were analyzed by high pressure liquid chromatography. EPN and its metabolites were identified by comparing their ultraviolet absorbance with those of standards. Qualitative differences in EPN metabolism were not noted in chicken and rat microsomal preparations but there were quantitative differences. EPN metabolism did not occur in the absence of NADPH. EPNO formation was faster in rat microsomes than with chicken microsomes; hydrolysis of EPNO was rapid in rat preparations but absent in chicken preparations. The authors suggest that the differences in EPNO metabolism in rats and chickens may account for the sensitivity of chickens to delayed neurotoxicity induced by EPN.
NIOSH-Publication; NIOSH-Grant; Laboratory-techniques; Chemical-analysis; Analytical-instruments; Chromatographic-analysis; Chemical-agent-detectors; Chemical-structure
Pharmacology Duke University Department of Pharmacology Durham, N C 27710
Duke University, Durham, North Carolina