Experimental Studies on Dimethoate Oxidative Desulfuration

Abstract

Dimethoate (DM) is biotransformed to an anti-cholinesterase oxoanalogue via liver cytochrome P-450 system. The present investigation deals with a semi-quantitative method for estimating this oxidative desulfuration: DM incubation with liver microsomes and co-factors at optimized concentrations and conditions yields oxo-DM. This is quantitatively expressed by the inhibition of serum cholinesterase activity (ChEA). Concentration and time effects on the reaction rates were studied in vitro. The calculated kinetic parameters pointed to a high affinity of P-450 for DM. The relationship between various substrates of the P-450 system were studied as well. Concentrations of 0.1 to 10 mM DM led to a linear decrease of the rates of N-demethylation and p-hydroxylation. Similar effects were observed in microsomes from rats treated with DM in vivo where a higher capacity for DM biotransformation was found. This capacity increases with a high initial rate after the treatment inspite of the decreasing P-450 quantity as measured by CO-binding spectra. On the third hour after a single dose of 1.5 mg/kg DM desulfuration activity reached 140% as compared with control values (p<0.01), while aniline hydroxylation, aminopyrine N-demethylation and P-450 were 78%, 76%, and 67%, respectively, (p<0.01). Microsomal protein remained practically unchanged.