Role of Carboxylesterase in Protection against Soman Toxicity

Abstract

Rats were injected intraperitoneally with phenobarbital (PB) and 3-methylchol-anthrene (MC) which are microsomal enzyme inducers, and methyl iodide (Mel), cobalt chloride (COCI₂) and tri-o-cresyl phosphate (TOCP) which are inhibitors of the enzymes glutathione transferase, cytochrome (cyt) P-450 and carboxylesterase, respectively, and then challenged with soman (i.p.) to know its LD₅₀. Pretreatment with PB and MC increased and TOCP decreased, whereas Mel as well as COCI₂ did not alter the LD50 value of soman in rats. The ½LD₅₀ dose of soman did not affect the liver microsomal cyt P-450 level, but significantly lowered carboxylesterase (CaE) and cholinesterase (ChE) activities in liver microsomes and in blood plasma. Induction of plasma CaE was more important than microsomal CaE in PB-mediated protection against soman toxicity. Gel filtration of plasma into four protein fractions for their relative soman binding capacity showed that a high-molecular-weight protein fraction (180,000 daltons on SDS-PAGE) which had no CaE activity could bind soman 6 times more than the low-molecular-weight CaE-containing protein fraction (60,000 daltons on SDS-PAGE).

Tissue-Specific Effects of Chlorpyrifos on Carboxylesterase and Cholinesterase Activity in Adult Rats: An in Vitro and in Vivo Comparison

“…Since that time, many groups have investigated the possible role of CaE in antiChE toxicity. It is now clear that CaE is capable of altering the toxicity profile of many nerve agents (Clement, 1984a,b;Fonnum et al, 1985;Gupta and Dettbarn, 1987;Jimmerson et al, 1989;Purshottam and Srivastava, 1989;Clement and Erhardt, 1990;Maxwell, 1992aMaxwell, , 1987a and some anticholinesterase pesticides (e.g., Gupta and Kadel, 1989;Chambers et al, 1990;Gupta and Dettbarn, 1993).…”