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Toxicokinetics and bioavailability of indoxacarb enantiomers and their new metabolites in rats.
Ai, Jiao; Li, Jianxin; Chang, Alan Kueichieh; Pei, Ying; Li, Haoran; Liu, Kai; Li, Ruiyun; Xu, Liuping; Wang, Nan; Liu, Yuhui; Su, Weiping; Liu, Wenbao; Wang, Tingting; Jiang, Zhen; Chen, Lijiang; Liang, Xiao.
Afiliação
  • Ai J; School of Pharmaceutical Sciences, Liaoning University, 66 Chongshan Road, Shenyang 110036, Liaoning Province, PR China.
  • Li J; School of Pharmaceutical Sciences, Liaoning University, 66 Chongshan Road, Shenyang 110036, Liaoning Province, PR China.
  • Chang AK; College of Life and Environmental Sciences, Wenzhou University, Wenzhou 325035, Zhejiang Province, PR China.
  • Pei Y; School of Pharmaceutical Sciences, Liaoning University, 66 Chongshan Road, Shenyang 110036, Liaoning Province, PR China.
  • Li H; School of Pharmaceutical Sciences, Liaoning University, 66 Chongshan Road, Shenyang 110036, Liaoning Province, PR China.
  • Liu K; School of Pharmaceutical Sciences, Liaoning University, 66 Chongshan Road, Shenyang 110036, Liaoning Province, PR China.
  • Li R; School of Pharmaceutical Sciences, Liaoning University, 66 Chongshan Road, Shenyang 110036, Liaoning Province, PR China.
  • Xu L; School of Pharmaceutical Sciences, Liaoning University, 66 Chongshan Road, Shenyang 110036, Liaoning Province, PR China.
  • Wang N; School of Pharmaceutical Sciences, Liaoning University, 66 Chongshan Road, Shenyang 110036, Liaoning Province, PR China.
  • Liu Y; School of Pharmaceutical Sciences, Liaoning University, 66 Chongshan Road, Shenyang 110036, Liaoning Province, PR China.
  • Su W; School of Pharmaceutical Sciences, Liaoning University, 66 Chongshan Road, Shenyang 110036, Liaoning Province, PR China.
  • Liu W; School of Pharmaceutical Sciences, Liaoning University, 66 Chongshan Road, Shenyang 110036, Liaoning Province, PR China.
  • Wang T; School of Pharmaceutical Sciences, Liaoning University, 66 Chongshan Road, Shenyang 110036, Liaoning Province, PR China.
  • Jiang Z; Department of Analytical Chemistry, College of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, Liaoning Province, PR China.
  • Chen L; School of Pharmaceutical Sciences, Liaoning University, 66 Chongshan Road, Shenyang 110036, Liaoning Province, PR China. Electronic address: clj1172023@163.com.
  • Liang X; School of Pharmaceutical Sciences, Liaoning University, 66 Chongshan Road, Shenyang 110036, Liaoning Province, PR China. Electronic address: liangxiao3232@163.com.
Pestic Biochem Physiol ; 203: 106024, 2024 Aug.
Article em En | MEDLINE | ID: mdl-39084783
ABSTRACT
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Oxazinas / Disponibilidade Biológica / Ratos Sprague-Dawley / Toxicocinética / Inseticidas Limite: Animals Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Oxazinas / Disponibilidade Biológica / Ratos Sprague-Dawley / Toxicocinética / Inseticidas Limite: Animals Idioma: En Ano de publicação: 2024 Tipo de documento: Article