Protective action by thiouracil against the acute toxicity in mice of O-ethyl O-(4-nitrophenyl) phenylphosphonothioate (EPN)

Michael H. Kelemen; Robert L. Volle

doi:10.1016/0041-008X(65)90143-2

Protective action by thiouracil against the acute toxicity in mice of O-ethyl O-(4-nitrophenyl) phenylphosphonothioate (EPN)

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Abstract

Pretreatment with thiouracil provided significant protection to mice treated subsequently with the organophosphorus insecticide EPN. Uracil did not share the protective properties of thiouracil. Although other mechanisms are possible, the protective action of thiouracil is explained best by the working hypothesis that the oxidative desulfuration of thiouracil to form uracil interferes with a similar desulfuration of EPN and the formation of its pharmacologically active oxygen reaction product. Thiouracil also afforded some protection to mice against the acute toxicity of parathion. On the other hand, it had no protective action against the acute toxicity of the irreversible anticholinesterase compound, 217 AO. Treatment of mice with the metabolic inhibitor SKF 525A enhanced the lethal actions of EPN.

Original language	English (US)
Pages (from-to)	418-424
Number of pages	7
Journal	Toxicology and Applied Pharmacology
Volume	7
Issue number	3
DOIs	https://doi.org/10.1016/0041-008X(65)90143-2
State	Published - May 1965
Externally published	Yes

ASJC Scopus subject areas

Toxicology
Pharmacology

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10.1016/0041-008X(65)90143-2

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title = "Protective action by thiouracil against the acute toxicity in mice of O-ethyl O-(4-nitrophenyl) phenylphosphonothioate (EPN)",

abstract = "Pretreatment with thiouracil provided significant protection to mice treated subsequently with the organophosphorus insecticide EPN. Uracil did not share the protective properties of thiouracil. Although other mechanisms are possible, the protective action of thiouracil is explained best by the working hypothesis that the oxidative desulfuration of thiouracil to form uracil interferes with a similar desulfuration of EPN and the formation of its pharmacologically active oxygen reaction product. Thiouracil also afforded some protection to mice against the acute toxicity of parathion. On the other hand, it had no protective action against the acute toxicity of the irreversible anticholinesterase compound, 217 AO. Treatment of mice with the metabolic inhibitor SKF 525A enhanced the lethal actions of EPN.",

author = "Kelemen, {Michael H.} and Volle, {Robert L.}",

note = "Funding Information: study was supported by research grant NB-03434-02 from the National Institute of Diseases and Blindness, National Institutes of Health, United States Public Health",

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AU - Kelemen, Michael H.

AU - Volle, Robert L.

N1 - Funding Information: study was supported by research grant NB-03434-02 from the National Institute of Diseases and Blindness, National Institutes of Health, United States Public Health

PY - 1965/5

Y1 - 1965/5

N2 - Pretreatment with thiouracil provided significant protection to mice treated subsequently with the organophosphorus insecticide EPN. Uracil did not share the protective properties of thiouracil. Although other mechanisms are possible, the protective action of thiouracil is explained best by the working hypothesis that the oxidative desulfuration of thiouracil to form uracil interferes with a similar desulfuration of EPN and the formation of its pharmacologically active oxygen reaction product. Thiouracil also afforded some protection to mice against the acute toxicity of parathion. On the other hand, it had no protective action against the acute toxicity of the irreversible anticholinesterase compound, 217 AO. Treatment of mice with the metabolic inhibitor SKF 525A enhanced the lethal actions of EPN.

AB - Pretreatment with thiouracil provided significant protection to mice treated subsequently with the organophosphorus insecticide EPN. Uracil did not share the protective properties of thiouracil. Although other mechanisms are possible, the protective action of thiouracil is explained best by the working hypothesis that the oxidative desulfuration of thiouracil to form uracil interferes with a similar desulfuration of EPN and the formation of its pharmacologically active oxygen reaction product. Thiouracil also afforded some protection to mice against the acute toxicity of parathion. On the other hand, it had no protective action against the acute toxicity of the irreversible anticholinesterase compound, 217 AO. Treatment of mice with the metabolic inhibitor SKF 525A enhanced the lethal actions of EPN.

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Protective action by thiouracil against the acute toxicity in mice of O-ethyl O-(4-nitrophenyl) phenylphosphonothioate (EPN)

Abstract

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