Intrinsic metabolic clearance of parathion and paraoxon by livers from fish and rodents

Kendall B Wallace, John E. Dargan

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

The specific activities of hepatic enzymes involved in both the activation and detoxification of the anticholinesterase insecticide parathion were significantly greater in both rats and mice compared to either fathead minnows or rainbow trout. Whereas the rates of parathion desulfuration and hydrolysis were comparable, the specific activity for paraoxon hydrolysis was approximately threefold greater than its rate of formation for all species except trout. The kinetic data, however, indicate that the significantly greater Km for paraoxon hydrolysis limits its detoxification. Accordingly, the data are consistent with the progressive accumulation of this toxic metabolite in liver tissue incubated in vitro with parathion. The similar Km for parathion desulfuration and hydrolysis by rodents is consistent with the proposed mechanism of catalysis involving a common S-oxide intermediate. Due to the slow rates of enzyme catalysis, reliable kinetic estimates for the hydrolytic reactions were not possible for both species of fish. Assuming comparable Km values for paraoxon hydrolysis in rodents and fish, the net accumulation of paraoxon in tissue water may be quite similar between species and metabolic transformation may not be an important determinant of the species-selective toxicity of parathion.

Original languageEnglish (US)
Pages (from-to)235-242
Number of pages8
JournalToxicology and Applied Pharmacology
Volume90
Issue number2
DOIs
StatePublished - Sep 15 1987

Bibliographical note

Funding Information:
The excellent clerical assistance provided by Susan J. Kurki is greatly appreciated. This work was supported by the U.S. Environmental Protection Agency CR-8 10963.

Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.

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