Exploring the binding mechanism and adverse toxic effects of degradation metabolites of pyrethroid insecticides to human serum albumin: Multi-spectroscopy, calorimetric and molecular docking approaches

Yiwen Cui; Yingying Sun; Hang Yu; Yahui Guo; Weirong Yao; Yunfei Xie; Fangwei Yang

doi:10.1016/j.fct.2023.113951

Exploring the binding mechanism and adverse toxic effects of degradation metabolites of pyrethroid insecticides to human serum albumin: Multi-spectroscopy, calorimetric and molecular docking approaches

Food Chem Toxicol. 2023 Sep:179:113951. doi: 10.1016/j.fct.2023.113951. Epub 2023 Jul 20.

Authors

Yiwen Cui¹, Yingying Sun², Hang Yu¹, Yahui Guo¹, Weirong Yao¹, Yunfei Xie³, Fangwei Yang⁴

Affiliations

¹ State Key Laboratory of Food Science and Resources, Jiangnan University, No.1800 Lihu Avenue, Wuxi, Jiangsu Province, 214122, China; School of Food Science and Technology, Jiangnan University, No.1800 Lihu Avenue, Wuxi, Jiangsu Province, 214122, China.
² Research Institute, Centre Testing International Group Co., Ltd., Shenzhen, 518000, China.
³ State Key Laboratory of Food Science and Resources, Jiangnan University, No.1800 Lihu Avenue, Wuxi, Jiangsu Province, 214122, China; School of Food Science and Technology, Jiangnan University, No.1800 Lihu Avenue, Wuxi, Jiangsu Province, 214122, China. Electronic address: xieyunfei@jiangnan.edu.cn.
⁴ State Key Laboratory of Food Science and Resources, Jiangnan University, No.1800 Lihu Avenue, Wuxi, Jiangsu Province, 214122, China; School of Food Science and Technology, Jiangnan University, No.1800 Lihu Avenue, Wuxi, Jiangsu Province, 214122, China; School of Food and Health, Beijing Technology & Business University (BTBU), 33 Fucheng Road, Haidian District, Beijing, 100048, China. Electronic address: fwyang@jiangnan.edu.cn.

PMID: 37479174
DOI: 10.1016/j.fct.2023.113951

Abstract

Pyrethroid insecticides (PIs), a class of structurally similar non-persistent organic pollutants, can be degraded and metabolized to more toxic, and longer half-life products. In this study, the binding interaction mechanisms between human serum albumin (HSA) and the main degradation metabolites of PIs, 3-phenoxybenzoic acid (3-PBA) and 4-fluoro-3-phenoxybenzoic acid (4-F-3-PBA), were studied by theoretical simulation and experimental verification. Steady state fluorescence spectra showed that the fluorescence quenching mechanism was static. According to the binding constant, 4-F-3-PBA (1.53 × 10⁵ L mol^-1) was bound more strongly to HSA than 3-PBA (1.42 × 10⁵ L mol^-1) in subdomain ⅡA (site I). It was found by isothermal titration calorimetry that the metabolites and HSA spontaneously combined mainly through hydrogen bond and van der Waals interaction. Ultraviolet absorption spectra and circular dichroism spectra showed that the metabolites caused slight changes in the microenvironment and conformation of HSA. The above results were proved by molecular docking. The toxicity properties of the metabolites were further analyzed by software, and 4-F-3-PBA was found to be more toxic than 3-PBA. Considering the high exposure level of these metabolites in food, the environment and human body, it is necessary to further explore the toxicity of PIs metabolites.

Keywords: Human serum albumin; Isothermal titration calorimetry; Molecular docking; Multispectral; Pesticide metabolites.

MeSH terms

Binding Sites
Calorimetry
Circular Dichroism
Humans
Insecticides*
Molecular Docking Simulation
Protein Binding
Serum Albumin, Human* / metabolism
Spectrometry, Fluorescence
Thermodynamics

Substances

Serum Albumin, Human
3-phenoxybenzoic acid
Insecticides
4-carboxybiphenyl ether