Gondhalekar Ameya D, Nakayasu Ernesto S, Silva Isabel, Cooper Bruce, Scharf Michael E
Department of Entomology, Purdue University, 901 W. State St., West Lafayette, IN 47907, USA.
Metabolite Profiling Facility, Bindley Bioscience Center, Purdue University, 1201 W. State St., West Lafayette, IN 47907, USA.
Pestic Biochem Physiol. 2016 Nov;134:14-23. doi: 10.1016/j.pestbp.2016.05.003. Epub 2016 May 13.
Insecticides that are used for pest control undergo physical and biological (enzymatic) degradation. Indoxacarb is an oxadiazine class sodium channel blocker insecticide used for German cockroach (Blattella germanica L.) control. At present, no information is available on enzymatic biotransformation or metabolism of indoxacarb in this important urban pest. We studied the biotransformation pathways of indoxacarb in one susceptible and three field strains with varying susceptibility levels using liquid chromatography and high-resolution mass spectrometry. As shown in other insect species we found evidence for hydrolase-based bioactivation of indoxacarb to a toxic decarbomethoxylated metabolite, DCJW. In addition, both indoxacarb and DCJW were further metabolized to hydroxy, oxadiazine ring-opened and hydroxylated ring-opened metabolites. In general, higher indoxacarb disappearance, increased formation of DCJW and the above-mentioned metabolites were observed in the three field strains. In vitro biotransformation studies showed that hydroxylated and oxadiazine ring-opened metabolite formation is NADPH/cytochrome P450-dependent. Bioassays and in vivo metabolism experiments using the enzyme-inhibiting insecticide synergists, piperonyl butoxide (PBO) and S,S,S,-tributyl phosphorotrithioate (DEF), provided insights into potential indoxacarb resistance mechanisms that may proliferate in German cockroach field strains following unchecked selection pressures. The information presented here is an essential step toward developing indoxacarb resistance management programs and also reveals mechanisms of secondary/tertiary indoxacarb toxicity.
用于害虫防治的杀虫剂会经历物理和生物（酶促）降解。茚虫威是一种恶二嗪类钠通道阻滞剂杀虫剂，用于防治德国小蠊（德国小蠊L.）。目前，关于茚虫威在这种重要城市害虫中的酶促生物转化或代谢尚无相关信息。我们使用液相色谱和高分辨率质谱研究了茚虫威在一个敏感品系和三个具有不同敏感性水平的田间品系中的生物转化途径。正如在其他昆虫物种中所显示的，我们发现了茚虫威基于水解酶生物活化生成有毒的脱甲氧羰基代谢物DCJW的证据。此外，茚虫威和DCJW都进一步代谢为羟基、恶二嗪环开环和羟基化环开环代谢物。一般来说，在三个田间品系中观察到茚虫威消失更快，DCJW以及上述代谢物的生成增加。体外生物转化研究表明，羟基化和恶二嗪环开环代谢物的形成依赖于NADPH/细胞色素P450。使用酶抑制性杀虫剂增效剂胡椒基丁醚（PBO）和三丁基三硫代磷酸酯（DEF）进行的生物测定和体内代谢实验，为茚虫威潜在的抗性机制提供了见解，这些机制可能在德国小蠊田间品系中因未加控制的选择压力而扩散。本文提供的信息是制定茚虫威抗性管理计划的重要一步，同时也揭示了茚虫威二级/三级毒性的机制。
