Glucuronidation mechanisms in the rat and their significance in the metabolism of insecticides

Abstract

Optimum conditions for the in vitro glucuronidation of 1-naphthol were established using rat liver and small intestine as enzyme sources. The liver enzyme system was used to study conjugative metabolism, per se, and in conjunction with oxidative metabolism, while the intestine enzyme was used to study conjugative metabolism exclusively. Both carbaryl and Banol required oxidative metabolism before conjugation could take place. However, when conjugative metabolism was reduced by limiting the UDPGA concentration, the overall rate of carbamate metabolism was decreased. There was no accumulation of the nonconjugate metabolites although excess NADPH 2 was present in the microsome system. Inhibition of the conjugating enzymes was demonstrated using several insecticide synergists, including sulfoxide, piperonyl butoxide, and MGK-264, which are established mixed-function oxidase inhibitors. A number of insecticides at 10 −3 M concentration had no effect on the in vitro conjugating enzyme systems. Glucuronides of several hydroxylated carbaryl metabolites were synthesized by the enzymes from the two sources but the 5,6-dihydro-dihydroxy analog of carbaryl could not be conjugated.