In vitro sequestration of two organophosphorus homologs by the rat liver.

P Santhoshkumar, T Shivanandappa

Index: Chem. Biol. Interact. 119-120 , 277-82, (1999)

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Abstract

Bromophos (Bp) and ethylbromophos (EBp) are two structurally homologous organophosphorus insecticides (OP) which show a 24-fold difference in their toxicity to the laboratory rat (LD50--2215 and 91 mg/kg b.w., respectively). The role of rat liver in the sequestration of the OP oxons was studied based on carboxylesterase (CaE) inhibition in vitro. Bromoxon (Bo) and ethylbromoxon (EBo) were greater inhibitors of rat hepatic CaE than brain acetylcholinesterase (AChE) with IC50 values at nanomolar and picomolar levels, respectively. The capacity of the liver to sequester OPs was determined by measuring AChE inhibition pre-incubated with or without liver homogenate. AChE inhibition by Bo decreased with increasing concentration of liver tissue, whereas it was unaffected in the case of EBo. The results imply that liver tissue contains binding sites, which sequester Bo thereby reducing the number of OP molecules available to inhibit AChE. Although CaE inhibition leads to sequestration, other binding sites in the liver may have a significant role in determining the toxicity of OPs. Differential sequestration of the OPs by hepatic tissue, therefore, could be important in understanding the role of differential saturation of the target molecules, which has a bearing on differential toxicity.