Ruyun Liu, Jun Shang, Ke Gao*, Wei Li, Shiyuan Wang and Liping Lu,
{"title":"新烟碱类及其代谢物通过血脑脊液屏障渗透效率的第一个证据","authors":"Ruyun Liu, Jun Shang, Ke Gao*, Wei Li, Shiyuan Wang and Liping Lu, ","doi":"10.1021/acs.estlett.5c00558","DOIUrl":null,"url":null,"abstract":"<p >The ability of exogenous compounds to cross the blood–cerebrospinal fluid barrier (BCSFB) is a crucial factor in evaluating their potential neurotoxic risks. To date, limited research has reported the presence of parent neonicotinoids (p-NEOs) and metabolite NEOs (m-NEOs) in cerebrospinal fluid (CSF), not to mention their penetration efficiencies across BCSFB. Nine p-NEOs and 5 m-NEOs were measured in 159 paired serum and CSF samples. Seven p-NEOs and 5 m-NEOs were frequently detected in serum (median of 0.030–0.295 ng/mL), while 5 p-NEOs and 5 m-NEOs were commonly found in CSF (median of 0.032–0.283 ng/mL). Notably, concentrations of imidacloprid-olefin and acetamiprid-<i>N</i>-desmethyl exceeded those of imidacloprid (IMI) and acetamiprid (ACE), indicating that IMI and ACE predominantly existed as metabolites. The ratios (<i>R</i><sub>CSF/serum</sub>) of NEO concentrations in CSF to those in paired serum were used to estimate penetration efficiencies across BCSFB. Their <i>R</i><sub>CSF/serum</sub> (median of 0.468–0.992) were positively correlated with log <i>P</i> (<i>r</i> = 0.673, <i>p</i> = 0.033) while negatively correlated with water solubility (<i>r</i> = −0.745, <i>p</i> = 0.013), highlighting lipophilicity as a principal factor influencing BCSFB penetration. Additionally, <i>R</i><sub>CSF/serum</sub> was significantly correlated with white blood cell count in CSF. This study provided a unique delineation of differential behaviors of p-NEOs and m-NEOs in crossing BCSFB, offering a novel perspective on their neurotoxic risks.</p>","PeriodicalId":37,"journal":{"name":"Environmental Science & Technology Letters Environ.","volume":"12 8","pages":"930–936"},"PeriodicalIF":8.8000,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"First Evidence on the Penetration Efficiencies of Parent Neonicotinoids and Their Metabolites across the Blood–Cerebrospinal Fluid Barrier\",\"authors\":\"Ruyun Liu, Jun Shang, Ke Gao*, Wei Li, Shiyuan Wang and Liping Lu, \",\"doi\":\"10.1021/acs.estlett.5c00558\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >The ability of exogenous compounds to cross the blood–cerebrospinal fluid barrier (BCSFB) is a crucial factor in evaluating their potential neurotoxic risks. To date, limited research has reported the presence of parent neonicotinoids (p-NEOs) and metabolite NEOs (m-NEOs) in cerebrospinal fluid (CSF), not to mention their penetration efficiencies across BCSFB. Nine p-NEOs and 5 m-NEOs were measured in 159 paired serum and CSF samples. Seven p-NEOs and 5 m-NEOs were frequently detected in serum (median of 0.030–0.295 ng/mL), while 5 p-NEOs and 5 m-NEOs were commonly found in CSF (median of 0.032–0.283 ng/mL). Notably, concentrations of imidacloprid-olefin and acetamiprid-<i>N</i>-desmethyl exceeded those of imidacloprid (IMI) and acetamiprid (ACE), indicating that IMI and ACE predominantly existed as metabolites. The ratios (<i>R</i><sub>CSF/serum</sub>) of NEO concentrations in CSF to those in paired serum were used to estimate penetration efficiencies across BCSFB. Their <i>R</i><sub>CSF/serum</sub> (median of 0.468–0.992) were positively correlated with log <i>P</i> (<i>r</i> = 0.673, <i>p</i> = 0.033) while negatively correlated with water solubility (<i>r</i> = −0.745, <i>p</i> = 0.013), highlighting lipophilicity as a principal factor influencing BCSFB penetration. Additionally, <i>R</i><sub>CSF/serum</sub> was significantly correlated with white blood cell count in CSF. This study provided a unique delineation of differential behaviors of p-NEOs and m-NEOs in crossing BCSFB, offering a novel perspective on their neurotoxic risks.</p>\",\"PeriodicalId\":37,\"journal\":{\"name\":\"Environmental Science & Technology Letters Environ.\",\"volume\":\"12 8\",\"pages\":\"930–936\"},\"PeriodicalIF\":8.8000,\"publicationDate\":\"2025-07-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Environmental Science & Technology Letters Environ.\",\"FirstCategoryId\":\"1\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acs.estlett.5c00558\",\"RegionNum\":2,\"RegionCategory\":\"环境科学与生态学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENGINEERING, ENVIRONMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Environmental Science & Technology Letters Environ.","FirstCategoryId":"1","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acs.estlett.5c00558","RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, ENVIRONMENTAL","Score":null,"Total":0}
引用次数: 0
摘要
外源性化合物穿过血-脑脊液屏障(BCSFB)的能力是评估其潜在神经毒性风险的关键因素。迄今为止,有限的研究报道了母体新烟碱类(p- neo)和代谢物新烟碱类(m- neo)在脑脊液(CSF)中的存在,更不用说它们在BCSFB中的渗透效率了。在159个配对的血清和脑脊液样本中检测了9个p- neo和5个m- neo。血清中常检出7个p-NEOs和5个m-NEOs(中位数为0.030 ~ 0.295 ng/mL),脑脊液中常检出5个p-NEOs和5个m-NEOs(中位数为0.032 ~ 0.283 ng/mL)。值得注意的是,吡虫啉-烯烃和啶虫啉- n -二甲基的浓度超过了吡虫啉(IMI)和啶虫啉(ACE),表明IMI和ACE主要作为代谢物存在。使用脑脊液中NEO浓度与配对血清中NEO浓度的比值(RCSF/血清)来估计BCSFB的穿透效率。RCSF/血清(中位数为0.468-0.992)与对数P正相关(r = 0.673, P = 0.033),与水溶性负相关(r = - 0.745, P = 0.013),表明亲脂性是影响BCSFB渗透的主要因素。此外,RCSF/血清与CSF白细胞计数显著相关。该研究提供了p- neo和m- neo在穿越BCSFB时不同行为的独特描述,为其神经毒性风险提供了新的视角。
First Evidence on the Penetration Efficiencies of Parent Neonicotinoids and Their Metabolites across the Blood–Cerebrospinal Fluid Barrier
The ability of exogenous compounds to cross the blood–cerebrospinal fluid barrier (BCSFB) is a crucial factor in evaluating their potential neurotoxic risks. To date, limited research has reported the presence of parent neonicotinoids (p-NEOs) and metabolite NEOs (m-NEOs) in cerebrospinal fluid (CSF), not to mention their penetration efficiencies across BCSFB. Nine p-NEOs and 5 m-NEOs were measured in 159 paired serum and CSF samples. Seven p-NEOs and 5 m-NEOs were frequently detected in serum (median of 0.030–0.295 ng/mL), while 5 p-NEOs and 5 m-NEOs were commonly found in CSF (median of 0.032–0.283 ng/mL). Notably, concentrations of imidacloprid-olefin and acetamiprid-N-desmethyl exceeded those of imidacloprid (IMI) and acetamiprid (ACE), indicating that IMI and ACE predominantly existed as metabolites. The ratios (RCSF/serum) of NEO concentrations in CSF to those in paired serum were used to estimate penetration efficiencies across BCSFB. Their RCSF/serum (median of 0.468–0.992) were positively correlated with log P (r = 0.673, p = 0.033) while negatively correlated with water solubility (r = −0.745, p = 0.013), highlighting lipophilicity as a principal factor influencing BCSFB penetration. Additionally, RCSF/serum was significantly correlated with white blood cell count in CSF. This study provided a unique delineation of differential behaviors of p-NEOs and m-NEOs in crossing BCSFB, offering a novel perspective on their neurotoxic risks.
期刊介绍:
Environmental Science & Technology Letters serves as an international forum for brief communications on experimental or theoretical results of exceptional timeliness in all aspects of environmental science, both pure and applied. Published as soon as accepted, these communications are summarized in monthly issues. Additionally, the journal features short reviews on emerging topics in environmental science and technology.