The effect of 2-(o-Cresyl)-4H-1:3:2-benzodioxaphosphorin-2-oxide on tissue cholinesterase and carboxylesterase activities of the rat

V. R. Jimmerson, T. M. Shih, D. M. Maxwell, A. Kaminskis, Richard Mailman

Research output: Contribution to journalArticle

Abstract

The dose-response (0.1 to 1000 mg/kg sc) effects of 2-(o-cresyl)-4H-l:3:2-benzodioxaphosphorin-2-oxide (CBDP; a melabolite of the organophosphorus compound tri-o-cresylphosphare on total cholinesterase (ChE) and carboxylesterase (CaE) activities in tissues from the rat were examined. Doses of CBDP greater than 1.0 mg/kg inhibited CaE activity maximally (>99%) in plasma and lung, two important sites for detoxification of organophosphorus toxicants. A biphasic dose-dependent inhibition of ChE activity was seen in all tissues; the ED5O values showed a difference of two orders of magnitude between the first and the second phases of the dose-response curves. CBDP inhibited the blood esterases in the order plasma CaE {black right-pointing small triangle} plasma ChE {black right-pointing small triangle} red blood cell (RBC) ChE. The biphasic dose-response curve and preferential inhibition of the blood esterases may reflect the inhibition of butyryicholinesterase in preference to acetylcholinesterase in these tissues. At doses of CBDP below 1.0 mg/kg, plasma, RBC, and brain regional ChE activities were inhibited by less than 10%, whereas at doses above 2.0 mg/kg, ChE activities were inhibited substantially (up to 80% in plasma, up to 60% in RBC, and greater than 90% in brain regions). On the basis of these results, a dose of CBDP between 1.0 and 2.0 mg/kg should prove useful as a pretreatment for studies of OP toxicity in the rat.

Original languageEnglish (US)
Pages (from-to)568-575
Number of pages8
JournalToxicological Sciences
Volume13
Issue number3
DOIs
StatePublished - Oct 1 1989

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Carboxylesterase
Cholinesterases
Rats
Tissue
Blood
Plasmas
Erythrocytes
Esterases
Brain
Organophosphorus Compounds
Detoxification
Acetylcholinesterase
Oxides
Toxicity
2-(2-cresyl)-4H-1-3-2-benzodioxaphosphorin-2-oxide
Cells
Lung

All Science Journal Classification (ASJC) codes

  • Toxicology

Cite this

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title = "The effect of 2-(o-Cresyl)-4H-1:3:2-benzodioxaphosphorin-2-oxide on tissue cholinesterase and carboxylesterase activities of the rat",
abstract = "The dose-response (0.1 to 1000 mg/kg sc) effects of 2-(o-cresyl)-4H-l:3:2-benzodioxaphosphorin-2-oxide (CBDP; a melabolite of the organophosphorus compound tri-o-cresylphosphare on total cholinesterase (ChE) and carboxylesterase (CaE) activities in tissues from the rat were examined. Doses of CBDP greater than 1.0 mg/kg inhibited CaE activity maximally (>99{\%}) in plasma and lung, two important sites for detoxification of organophosphorus toxicants. A biphasic dose-dependent inhibition of ChE activity was seen in all tissues; the ED5O values showed a difference of two orders of magnitude between the first and the second phases of the dose-response curves. CBDP inhibited the blood esterases in the order plasma CaE {black right-pointing small triangle} plasma ChE {black right-pointing small triangle} red blood cell (RBC) ChE. The biphasic dose-response curve and preferential inhibition of the blood esterases may reflect the inhibition of butyryicholinesterase in preference to acetylcholinesterase in these tissues. At doses of CBDP below 1.0 mg/kg, plasma, RBC, and brain regional ChE activities were inhibited by less than 10{\%}, whereas at doses above 2.0 mg/kg, ChE activities were inhibited substantially (up to 80{\%} in plasma, up to 60{\%} in RBC, and greater than 90{\%} in brain regions). On the basis of these results, a dose of CBDP between 1.0 and 2.0 mg/kg should prove useful as a pretreatment for studies of OP toxicity in the rat.",
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The effect of 2-(o-Cresyl)-4H-1:3:2-benzodioxaphosphorin-2-oxide on tissue cholinesterase and carboxylesterase activities of the rat. / Jimmerson, V. R.; Shih, T. M.; Maxwell, D. M.; Kaminskis, A.; Mailman, Richard.

In: Toxicological Sciences, Vol. 13, No. 3, 01.10.1989, p. 568-575.

Research output: Contribution to journalArticle

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