Oxidase Activities in Macrocyclic-Resistant and -Susceptible Haemonchus contortus

The role of oxidative metabolism in resistance to macrocyclic lactones in Haemonchus contortus was examined by measuring activities toward 2 model cytochrome P450 substrates, aldrin and ethoxycoumarin, in a susceptible and a resistant isolate of the parasite. Microsomal preparations from larvae and adults of the 2 isolates showed no differences in levels of NADPH- or cumene hydroperoxide-supported aldrin epoxidase or ethoxycoumarin O-deethylase activities. Intact adult nematodes showed an ability to catalyze the epoxidation of significant amounts of aldrin, although the nature of the enzyme group responsible was unknown. This epoxidase activity was greater in adults of the susceptible isolate. It is apparent that oxidase activities toward the 2 substrates are not enhanced in the resistant isolate, suggesting that the observed resistance to macrocyclic lactones may not involve enhanced oxidative metabolism.