NATURE AND ROLE OF XENOBIOTIC METABOLIZING ESTERASES IN RAT-LIVER, LUNG, SKIN AND BLOOD

In the present study, the distribution and nature of esterases in the rat which hydrolysed fluazifop-butyl, carbaryl, paraoxon and phenylacetate were investigated. V(max) and K(m) values for the hydrolysis reactions were determined. Fluazifop-butyl was hydrolysed to fluazifop by rat liver (V(max) mumol/min/g microsomes 6.2 +/- 0.4; cytosol 6.84 +/- 0.85), lung (V(max) microsomes 0.38 +/- 0.1; cytosol 1.5 +/- 0.32) and skin (V(max) microsomes 0.02 +/- 0.0015; cytosol 0.4 +/- 0.06) and by plasma (V(max) mumol/min/mL 5.8 +/- 0.48) and red blood cells (V(max) 0.03 +/- 0.015). Significant inhibition by paraoxon and bismitrophenol phosphate indicated the involvement of carboxylesterases. Carbaryl was hydrolysed by liver, lung and skin at a lower rate by microsomal fractions (V(max) nmol/min/g 2.1 +/- 0.25, 1.6 +/- 0.25, 0.2 +/- 0.035, respectively) compared to cytosolic fractions (V(max) 6.7 +/- 0.75, 1.4 +/- 0.36, 0.5 +/- 0.12) and plasma (V(max) nmol/min/mL 3.0 +/- 0.25). Hydrolysis involved carboxylesterases. Paraoxon was hydrolysed by paraoxonases/arylesterases only in the plasma (V(max) nmol/min/mL 246 +/- 12) and microsomal fractions from liver (V(max) 330 nmol/min/g +/- 25) and lung (V(max) 2 +/- 0.25). Phenylacetate was hydrolysed by both microsomal and cytosolic fractions from all tissues studied. Hydrolysis involved arylesterases in the microsomes and carboxylesterases in the cytosol. Extrahepatic hydrolysis may be important following some routes of exposure to xenobiotic esters.