Effects of the Synergists Piperonyl Butoxide and <I>S</I>,<I>S</I>,<I>S</I>-Tributyl Phosphorotrithioate on Propoxur Pharmacokinetics in <I>Blattella germanica</I> (Blattodea: Blattellidae)

Abstract

Effects of the synergists piperonyl butoxide (PBO) and S,S,S-tributyl phosphorotrithioate (DEF) on propoxur pharmacokinetics were examined in the German cockroach, Blattella germanica (L.). Treatment of adult male German cockroaches with the cytochrome P450 monooxygenase inhibitor, PBO, or the esterase inhibitor, DEF, increased propoxur toxicity by 2- and 6.8-fold, respectively, implicating hydrolysis as a major detoxification route of propoxur in the German cockroach. However, significant hydrolytic metabolism could not be demonstrated conclusively in vitro resulting in a conflict between in situ bioassay data and in vitro metabolic studies. In vitro propoxur metabolism with NADPH-fortified microsomes produced at least nine metabolites. Formation of metabolites was NADPH-dependent; no quantifiable metabolism was detected with cytosolic fractions. However, microsomal fractions lacking an NADPH source did produce a low, but detectable, quantity of metabolites (1.6 pmol). PBO inhibited NADPH-dependent propoxur metabolism in a dose-dependent fashion, implicating cytochrome P450 monooxygenases as the enzyme system responsible for the metabolism. Interestingly, DEF also inhibited the NADPH-dependent metabolism of propoxur, albeit to a lower extent. Treatment with PBO or DEF also caused a significant reduction in the cuticular penetration rate of propoxur. The data demonstrate that unanticipated effects are possible with synergists and that caution must be exercised when interpreting synergist results.

Mechanisms of Pyrethroid Resistance in the Dengue Mosquito Vector, Aedes aegypti: Target Site Insensitivity, Penetration, and Metabolism

“…We therefore examined the effects of PBO on permethrin penetration and showed that it did not enhance permethrin penetration, but instead suppressed the rate of its penetration (Figure 2). This finding is consistent with other reports on the German cockroach [64] and house fly [65]–[67]. We also found that permethrin penetration was markedly suppressed by PBO treatment, even administered on the thoracic sternum of the insect followed by permethrin treatment on the thoracic notum.…”

Insecticide Resistance Profiles and Synergism in Field Populations of the German Cockroach (Dictyoptera: Blattellidae) From Singapore

“…These results suggest the contribution of both enhanced oxidative and hydrolytic metabolism to propoxur resistance in German cockroach populations in Singapore. Sánchez-Arroyo et al (2001) previously reported that both oxidative and hydrolytic enzymes are associated with the detoxiÞ-cation of propoxur.…”

The biology of insecticidal activity and resistance

“…Establishing the resistance phenotype is metabolic Initial testing for the involvement of detoxification mechanisms in insecticide resistance is often performed by co-administration of the insecticide and a synergist, for example piperonyl butoxide (PBO) which inhibits the activity of P450 enzymes, or diethyl maleate (DEM) which inhibits the activity of GST enzymes. A reduction in insecticide concentration needed to kill an insect due to the administration of a synergist implies the involvement of a particular class of enzyme in resistance (Liu and Yue, 2000;Pasay et al, 2009;Sanchez-Arroyo et al, 2001). It fails to identify the individual enzyme responsible for resistance however.…”