The global use of pesticides is increasing; however, few studies have examined the exposure of current-use pesticide exposure in Inuit populations. Some current use pesticides are also capable of long-range transport, potentially increasing exposures to northern populations. The study aim was to analyse pesticide (chlorophenoxy, organophosphates, and pyrethroid pesticide) biomarker levels in pooled samples from an Inuit population in Nunavik, Quebec. Thirty pooled samples from the Qanuilirpitaa? 2017 survey (Q2017) from individuals aged 16-80 years were included. Creatinine-adjusted arithmetic (AM) were compared by sex, age, and region sub-groups, and geometric mean concentrations (GM) were compared to those in the Canadian Health Measures Survey (CHMS). Most analysed pesticide biomarkers were detected, and PNP (a metabolite of methyl and ethyl parathion), trans-DCCA (a metabolite of pyrethroids), and 3,5,6-TCP (a metabolite of chlorpyrifos) had the highest concentrations. Concentrations in Q2017 were largely similar to or less than CHMS concentrations. Although not significant, there was a general increase in 2,4-D (a chlorophenoxy biomarker), 3,5,6-TCP, 3-PBA (a metabolite of pyrethroids), and trans-DCCA with increasing age. Concentrations were also somewhat higher in females versus males, but these were not significant. Environmental exposures to current use pesticides were detected in Nunavik and concentrations were similar to or less than those in the general Canadian population. Regular monitoring of current use pesticide exposures is recommended given the increasing global use of pesticides.

01 Dec 2024·Science of The Total Environment

Comparative study of fenpropathrin and its main metabolite in soil-earthworm microcosms: Toxicity, degradation, transcriptome, and oxidative stress

Article

Author: Yang, Cancan ; Ran, LuLu ; Tang, Can ; Zhang, Ping ; Ke, Xiaojiang ; Xu, Zhifeng

This study comprehensively investigated the comparative acute toxicities, degradation, transcriptome, and oxidative stress induction of fenpropathrin (FEN) and its main metabolite 3-phenoxybenzoic acid (3-PBA)in soil-earthworm microcosms. FEN degradation half-life ranged from 19.09 to 28.52 days, and the peak-shaped trends of 3-PBA were also observed in different soil types. The LC₅₀ values of FEN and 3-PBA were 12.75 and 7.49 μg/cm², respectively, suggesting that 3-PBA was more toxic to earthworms. Furthermore, the sub-lethal toxicities indicated that 3-PBA exerted more prominent alterations in protein content, enzyme activity, lipid peroxidation, and oxidative stress in earthworms. Additionally, integrated biomarker response evaluations indicated that 3-PBA induced more prominent sub-lethal toxicity in earthworms than FEN. Finally, exposure to FEN and 3-PBA resulted in distinct differentially expressed genes (DEGs) in earthworms. Enrichment analysis revealed that these DEGs were predominantly enriched in purine metabolism and bile secretion pathways in earthworms. Moreover, the p53 signaling pathway, cell cycle, DNA replication, drug metabolism, and pyrimidine metabolism were also enriched in earthworms after exposure to FEN and 3-PBA. These results suggested that FEN and 3-PBA induced varying toxicities in earthworms. This study highlighted the systemic differences in the toxicities, degradation, transcriptome, and oxidative stress induction between FEN and 3-PBA in soil-earthworm microcosms. Our findings could be used for a comprehensive risk assessment of FEN and 3-PBA in the soil ecosystem.

01 Nov 2024·Bioorganic & Medicinal Chemistry

Inhibition of LPS-induced inflammatory response in RAW264.7 cells by natural Chlorogenic acid isomers involved with AKR1B1 inhibition

Article

Author: Chen, Huan ; Liu, Fanglin ; Hou, Hongwei ; Han, Xu ; Wu, Xiaqing

Inflammation is the physiological response of the immune system to injury or infection, typically manifested by local tissue congestion, swelling, heat, and pain. Prolonged or excessive inflammation can lead to tissue damage and the development of many diseases. The anti-inflammatory effects of natural ingredients have been extensively researched and confirmed. This study investigated the effects of Chlorogenic acid (CGA) isomers -- 3-Caffeolyquninic acid (3-CQA), 4-Caffeolyquninic acid (4-CQA), and 5-Caffeolyquninic acid (5-CQA) -- on the inflammatory response and oxidative stress reaction induced by LPS in RAW264.7 cells. Overall, 3-CQA exhibited the most significant reduction in levels of TNF-α, IL-6, NO, and ROS. 4-CQA showed superior inhibition of TNF-α compared to 5-CQA (p < 0.05), while no significant difference in other parameters. We further used DARTS and CETSA to demonstrate that CGA isomers have stable affinity with AKR1B1. As a positive control, the AKR1B1 antagonist epalrestat exhibited similar effects to the CGA isomers. 3-CQA having the smallest half-inhibitory concentration (IC50) for AKR1B1, while 4-CQA and 5-CQA have similar values. AutoDock simulations of the docking conformations revealed minimal differences in the average binding energies of the CGA isomers. The main differences were that VAL47 formed a hydrogen bond with 3-CQA, whereas GLN49 formed hydrogen bonds with 4-CQA and 5-CQA. Additionally, the number of hydrophobic bonds involving PHE122 and LEU300 varies. Our conclusion is that differences in non-covalent interactions result in the varying inhibitory abilities of CGA isomers on AKR1B1, which further affect the anti-inflammatory and antioxidant effects of CGA isomers.

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