Interactions of Fipronil within Fish and Insects: Experimental and Molecular Modeling Studies.

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2018
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Abstract
Fipronil is an efficient phenylpyrazole insecticide that acts on insect γ-aminobutyric acid (GABA) receptors (GABARs) and has low toxicity to mammals but high toxicity to nontarget organisms such as fish. To develop novel efficient low-toxicity insecticides, it is necessary to determine the detailed toxic mechanism at the molecular target level. In this work, methods including affinity chromatography, fluorescent-labeled binding assays, and molecular modeling were integrated to explore the binding of fipronil to GABARs in fish ( Aristichthys nobilis) and insects ( Musca domestica). Affinity chromatography revealed that fipronil acts on two different subunits of GABARs in fish and M. domestica. Moreover, fluorescence assays revealed that fipronil exhibits similar affinity to the two GABARs. The K and B of fipronil binding to the A. nobilis GABAR were 346 ± 6 nmol/L and 40.6 ± 3.5 pmol/mg of protein, respectively. And the K and B of fipronil binding to the GABAR in M. domestica brain were 109 ± 9 nM and 21.3 ± 2.5 pmol/mg of protein, respectively. In addition, similar fipronil binding positions but different binding modes were observed in docking studies with Brachydanio rerio var. and M. domestica GABARs. These findings indicated similar interactions of fipronil with fish and insects, leading to high toxicity. The different binding features of fipronil between the two species might be helpful for the design and development of highly selective insecticides with low toxicity to fish.
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zhang2018interactionsjournal Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Zhang, Bo;Zhang, Lei;He, Lujue;Yang, Xiaodong;Shi, Yali;Liao, Shaowei;Yang, Shan;Cheng, Jiagao;Ren, Tianrui;
Journal Journal of agricultural and food chemistry
Year 2018
DOI
10.1021/acs.jafc.8b00573
URL
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