Cresylbenzodioxaphosphorin oxide pretreatment alters soman-induced toxicity and inhibition of tissue cholinesterase activity of the rat

Vernon R. Jimmerson, Shih Tsung-Ming, Donald M. Maxwell, Richard Mailman

Research output: Contribution to journalArticle

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Abstract

The toxicity of soman was investigated in the rat with and without pretreatment with Cresylbenzodioxa-phosphorin oxide (CBDP). Without pretreatment, the 24-h LD50 for soman was 118.2 μg/kg s.c., and soman inhibited Carboxylesterase (CaE) activity in plasma (ED50 of 55 μg/kg) and cholinesterase (ChE) activity in brain regions (ED50 values of 65-105 μg/kg) in a dose-related manner. With pretreatment, the 24-h LD50 for soman was reduced by approximately 6-fold and 8-fold (by 1.0 mg/kg and 16.0 mg/kg of CBDP, respectively), and the ED50 values for soman-induced inhibition of ChE activity in brain regions were reduced by approximately 10-fold (by 1.0 mg/kg of CBDP). The dose-dependent severity of soman intoxication varied widely in rats treated with soman alone but not in CBDP-pretreated rats, and the ED50 for the occurrence of signs of soman intoxication was reduced approximately 7-fold following CBDP (1.0 mg/kg) pretreatment. These data support the hypothesis that CBDP pretreatment effectively blocks tissue CaE sites which serve to detoxify soman, thus potentiating both the soman-induced inhibition of ChE in the CNS and the lethality of soman.

Original languageEnglish (US)
Pages (from-to)93-103
Number of pages11
JournalToxicology Letters
Volume48
Issue number1
DOIs
StatePublished - Jan 1 1989

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Soman
Cholinesterases
Oxides
Toxicity
Rats
Tissue
Carboxylesterase
Lethal Dose 50
Brain
phosphate-binding proteolipid

All Science Journal Classification (ASJC) codes

  • Toxicology

Cite this

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title = "Cresylbenzodioxaphosphorin oxide pretreatment alters soman-induced toxicity and inhibition of tissue cholinesterase activity of the rat",
abstract = "The toxicity of soman was investigated in the rat with and without pretreatment with Cresylbenzodioxa-phosphorin oxide (CBDP). Without pretreatment, the 24-h LD50 for soman was 118.2 μg/kg s.c., and soman inhibited Carboxylesterase (CaE) activity in plasma (ED50 of 55 μg/kg) and cholinesterase (ChE) activity in brain regions (ED50 values of 65-105 μg/kg) in a dose-related manner. With pretreatment, the 24-h LD50 for soman was reduced by approximately 6-fold and 8-fold (by 1.0 mg/kg and 16.0 mg/kg of CBDP, respectively), and the ED50 values for soman-induced inhibition of ChE activity in brain regions were reduced by approximately 10-fold (by 1.0 mg/kg of CBDP). The dose-dependent severity of soman intoxication varied widely in rats treated with soman alone but not in CBDP-pretreated rats, and the ED50 for the occurrence of signs of soman intoxication was reduced approximately 7-fold following CBDP (1.0 mg/kg) pretreatment. These data support the hypothesis that CBDP pretreatment effectively blocks tissue CaE sites which serve to detoxify soman, thus potentiating both the soman-induced inhibition of ChE in the CNS and the lethality of soman.",
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Cresylbenzodioxaphosphorin oxide pretreatment alters soman-induced toxicity and inhibition of tissue cholinesterase activity of the rat. / Jimmerson, Vernon R.; Tsung-Ming, Shih; Maxwell, Donald M.; Mailman, Richard.

In: Toxicology Letters, Vol. 48, No. 1, 01.01.1989, p. 93-103.

Research output: Contribution to journalArticle

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AB - The toxicity of soman was investigated in the rat with and without pretreatment with Cresylbenzodioxa-phosphorin oxide (CBDP). Without pretreatment, the 24-h LD50 for soman was 118.2 μg/kg s.c., and soman inhibited Carboxylesterase (CaE) activity in plasma (ED50 of 55 μg/kg) and cholinesterase (ChE) activity in brain regions (ED50 values of 65-105 μg/kg) in a dose-related manner. With pretreatment, the 24-h LD50 for soman was reduced by approximately 6-fold and 8-fold (by 1.0 mg/kg and 16.0 mg/kg of CBDP, respectively), and the ED50 values for soman-induced inhibition of ChE activity in brain regions were reduced by approximately 10-fold (by 1.0 mg/kg of CBDP). The dose-dependent severity of soman intoxication varied widely in rats treated with soman alone but not in CBDP-pretreated rats, and the ED50 for the occurrence of signs of soman intoxication was reduced approximately 7-fold following CBDP (1.0 mg/kg) pretreatment. These data support the hypothesis that CBDP pretreatment effectively blocks tissue CaE sites which serve to detoxify soman, thus potentiating both the soman-induced inhibition of ChE in the CNS and the lethality of soman.

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