School of Pharmaceutical Sciences, Liaoning University, 66 Chongshan Road, Shenyang 110036, Liaoning Province, PR China.
College of Life and Environmental Sciences, Wenzhou University, Wenzhou 325035, Zhejiang Province, PR China.
Pestic Biochem Physiol. 2024 Aug;203:106024. doi: 10.1016/j.pestbp.2024.106024. Epub 2024 Jul 11.
Indoxacarb is a chiral insecticide that consists of two enantiomers, S-(+)-indoxacarb and R-(-)-indoxacarb, of which only S-(+)-indoxacarb has insecticidal activity. Previous enantioselective toxicology studies of indoxacarb focused mostly on simple environmental model organisms. The lack of a toxicology evaluation of indoxacarb conducted in a mammalian system could mean that the extent of the potential health risk posed by the insecticide to humans is not adequately known. In this study, we reported on a new pair of enantiomers, S-IN-RM294 and R-IN-RM294, derived from the metabolic breakdown of S-(+)-indoxacarb and R-(-)-indoxacarb, respectively, in rats. The toxicokinetics of S-(+)-indoxacarb, R-(-)-indoxacarb, S-IN-RM294, and R-IN-RM294 in rats were evaluated to provide a more comprehensive risk assessment of these molecules. The bioavailability and excretion rates of both S-(+)-indoxacarb and R-(-)-indoxacarb were relatively low, which may be due to their faster metabolism and accumulation in the tissues. In addition, there were significant differences in the metabolism and distribution between the two indoxacarb enantiomers and their metabolites in vivo. S-(+)-Indoxacarb was found to be more easily metabolized in the blood compared with R-(-)-indoxacarb, as shown by the differences in pharmacokinetic parameters between oral and intravenous administration. Analysis of their tissue distribution showed that S-(+)-indoxacarb was less likely to accumulate in most tissues. The results obtained for the two metabolites were consistent with those of the two parent compounds. S-IN-RM294 was more readily cleared from the blood and less likely to accumulate in the tissues compared with R-IN-RM294. Therefore, whether from the perspective of insecticidal activity or from the perspective of mammalian and environmental friendliness, the application of optically pure S-(+)-indoxacarb in agriculture may be a more efficient and safer strategy.
茚虫威是一种手性杀虫剂，由两种对映异构体 S-(+)-茚虫威和 R-(-)-茚虫威组成，其中只有 S-(+)-茚虫威具有杀虫活性。以前对茚虫威的对映选择性毒理学研究主要集中在简单的环境模式生物上。由于在哺乳动物系统中没有对茚虫威进行毒理学评估，这可能意味着人们对该杀虫剂对人类潜在健康风险的认识还不够充分。在这项研究中，我们报道了一对新的对映异构体 S-IN-RM294 和 R-IN-RM294，它们分别来自 S-(+)-茚虫威和 R-(-)-茚虫威在大鼠体内的代谢分解。评估了 S-(+)-茚虫威、R-(-)-茚虫威、S-IN-RM294 和 R-IN-RM294 在大鼠体内的毒代动力学，以更全面地评估这些分子的风险。S-(+)-茚虫威和 R-(-)-茚虫威的生物利用度和排泄率相对较低，这可能是由于它们在组织中的代谢和积累速度较快。此外，两种茚虫威对映异构体及其代谢物在体内的代谢和分布存在显著差异。与 R-(-)-茚虫威相比，S-(+)-茚虫威在血液中的代谢速度更快，这一点可以从口服和静脉给药时药代动力学参数的差异中看出。对它们的组织分布分析表明，S-(+)-茚虫威不太可能在大多数组织中积累。两种代谢物的结果与两种母体化合物的结果一致。与 R-IN-RM294 相比，S-IN-RM294 从血液中更迅速地清除，在组织中更不容易积累。因此，无论是从杀虫活性的角度，还是从哺乳动物和环境友好性的角度来看，在农业中应用光学纯 S-(+)-茚虫威可能是一种更有效和更安全的策略。
