UHPLC-HRMS(/MS)在墨西哥湾北部鱼类和人肝微粒体中体外I期brevetoxin(BTX-2)代谢产物的鉴定和跨物种比较

IF 3.6 Q2 TOXICOLOGY Toxicon: X Pub Date : 2023-09-01 DOI:10.1016/j.toxcx.2023.100168
Jessica Kay Gwinn , Alison Robertson , Lada Ivanova , Christiane Kruse Fæste , Fedor Kryuchkov , Silvio Uhlig
{"title":"UHPLC-HRMS(/MS)在墨西哥湾北部鱼类和人肝微粒体中体外I期brevetoxin(BTX-2)代谢产物的鉴定和跨物种比较","authors":"Jessica Kay Gwinn ,&nbsp;Alison Robertson ,&nbsp;Lada Ivanova ,&nbsp;Christiane Kruse Fæste ,&nbsp;Fedor Kryuchkov ,&nbsp;Silvio Uhlig","doi":"10.1016/j.toxcx.2023.100168","DOIUrl":null,"url":null,"abstract":"<div><p>Brevetoxins (BTX) are a group of marine neurotoxins produced by the harmful alga <em>Karenia brevis</em>. Numerous studies have shown that BTX are rapidly accumulated and metabolized in shellfish and mammals. However, there are only limited data on BTX metabolism in fish, despite growing evidence that fish serve as vectors for BTX transfer in marine food webs. In this study, we aimed to investigate the <em>in vitro</em> biotransformation of BTX-2, the major constituent of BTX profiles in <em>K. brevis</em>, in several species of northern Gulf of Mexico fish. Metabolism assays were performed using hepatic microsomes prepared in-house as well as commercially available human microsomes for comparison, focusing on phase I reactions mediated by cytochrome P450 monooxygenase (CYP) enzymes. Samples were analyzed by UHPLC-HRMS(/MS) to monitor BTX-2 depletion and characterize BTX metabolites based on MS/MS fragmentation pathways. Our results showed that both fish and human liver microsomes rapidly depleted BTX-2, resulting in a 72–99% reduction within 1 h of incubation. We observed the simultaneous production of 22 metabolites functionalized by reductions, oxidations, and other phase I reactions. We were able to identify the previously described congeners BTX-3 and BTX-B5, and tentatively identified BTX-9, 41,43-dihydro-BTX-2, several A-ring hydrolysis products, as well as several novel metabolites. Our results confirmed that fish are capable of similar BTX biotransformation reactions as reported for shellfish and mammals, but comparison of metabolite formation across the tested species suggested considerable interspecific variation in BTX-2 metabolism potentially leading to divergent BTX profiles. We additionally observed non-enzymatic formation of BTX-2 and BTX-3 glutathione conjugates. Collectively, these findings have important implications for determining the ecotoxicological fate of BTX in marine food webs.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":null,"pages":null},"PeriodicalIF":3.6000,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Identification and cross-species comparison of in vitro phase I brevetoxin (BTX-2) metabolites in northern Gulf of Mexico fish and human liver microsomes by UHPLC-HRMS(/MS)\",\"authors\":\"Jessica Kay Gwinn ,&nbsp;Alison Robertson ,&nbsp;Lada Ivanova ,&nbsp;Christiane Kruse Fæste ,&nbsp;Fedor Kryuchkov ,&nbsp;Silvio Uhlig\",\"doi\":\"10.1016/j.toxcx.2023.100168\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Brevetoxins (BTX) are a group of marine neurotoxins produced by the harmful alga <em>Karenia brevis</em>. Numerous studies have shown that BTX are rapidly accumulated and metabolized in shellfish and mammals. However, there are only limited data on BTX metabolism in fish, despite growing evidence that fish serve as vectors for BTX transfer in marine food webs. In this study, we aimed to investigate the <em>in vitro</em> biotransformation of BTX-2, the major constituent of BTX profiles in <em>K. brevis</em>, in several species of northern Gulf of Mexico fish. Metabolism assays were performed using hepatic microsomes prepared in-house as well as commercially available human microsomes for comparison, focusing on phase I reactions mediated by cytochrome P450 monooxygenase (CYP) enzymes. Samples were analyzed by UHPLC-HRMS(/MS) to monitor BTX-2 depletion and characterize BTX metabolites based on MS/MS fragmentation pathways. Our results showed that both fish and human liver microsomes rapidly depleted BTX-2, resulting in a 72–99% reduction within 1 h of incubation. We observed the simultaneous production of 22 metabolites functionalized by reductions, oxidations, and other phase I reactions. We were able to identify the previously described congeners BTX-3 and BTX-B5, and tentatively identified BTX-9, 41,43-dihydro-BTX-2, several A-ring hydrolysis products, as well as several novel metabolites. Our results confirmed that fish are capable of similar BTX biotransformation reactions as reported for shellfish and mammals, but comparison of metabolite formation across the tested species suggested considerable interspecific variation in BTX-2 metabolism potentially leading to divergent BTX profiles. We additionally observed non-enzymatic formation of BTX-2 and BTX-3 glutathione conjugates. Collectively, these findings have important implications for determining the ecotoxicological fate of BTX in marine food webs.</p></div>\",\"PeriodicalId\":37124,\"journal\":{\"name\":\"Toxicon: X\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2023-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Toxicon: X\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2590171023000206\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"TOXICOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Toxicon: X","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2590171023000206","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"TOXICOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

Brevetoxins(BTX)是由有害藻类Karenia brevis产生的一组海洋神经毒素。大量研究表明,BTX在贝类和哺乳动物中快速积累和代谢。然而,尽管越来越多的证据表明鱼类是海洋食物网中BTX转移的载体,但关于鱼类BTX代谢的数据有限。在这项研究中,我们旨在研究短鳍金枪鱼BTX图谱的主要成分BTX-2在墨西哥湾北部几种鱼类中的体外生物转化。使用内部制备的肝微粒体和市售的人微粒体进行代谢测定以进行比较,重点是细胞色素P450单加氧酶(CYP)介导的I期反应。通过UHPLC-HRMS(/MS)分析样品,以监测BTX-2的耗竭,并基于MS/MS裂解途径表征BTX代谢产物。我们的研究结果表明,鱼类和人类肝微粒体都迅速耗尽了BTX-2,在孵育1小时内减少了72–99%。我们观察到通过还原、氧化和其他I相反应同时产生22种功能化的代谢物。我们能够鉴定先前描述的同源物BTX-3和BTX-B5,并初步鉴定了BTX-9,41,4-二氢-BTX-2、几种A环水解产物以及几种新的代谢产物。我们的研究结果证实,鱼类能够进行与贝类和哺乳动物类似的BTX生物转化反应,但对测试物种代谢产物形成的比较表明,BTX-2代谢的种间差异很大,可能导致BTX图谱的差异。我们还观察到BTX-2和BTX-3谷胱甘肽缀合物的非酶促形成。总之,这些发现对确定BTX在海洋食物网中的生态毒理学命运具有重要意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

摘要图片

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Identification and cross-species comparison of in vitro phase I brevetoxin (BTX-2) metabolites in northern Gulf of Mexico fish and human liver microsomes by UHPLC-HRMS(/MS)

Brevetoxins (BTX) are a group of marine neurotoxins produced by the harmful alga Karenia brevis. Numerous studies have shown that BTX are rapidly accumulated and metabolized in shellfish and mammals. However, there are only limited data on BTX metabolism in fish, despite growing evidence that fish serve as vectors for BTX transfer in marine food webs. In this study, we aimed to investigate the in vitro biotransformation of BTX-2, the major constituent of BTX profiles in K. brevis, in several species of northern Gulf of Mexico fish. Metabolism assays were performed using hepatic microsomes prepared in-house as well as commercially available human microsomes for comparison, focusing on phase I reactions mediated by cytochrome P450 monooxygenase (CYP) enzymes. Samples were analyzed by UHPLC-HRMS(/MS) to monitor BTX-2 depletion and characterize BTX metabolites based on MS/MS fragmentation pathways. Our results showed that both fish and human liver microsomes rapidly depleted BTX-2, resulting in a 72–99% reduction within 1 h of incubation. We observed the simultaneous production of 22 metabolites functionalized by reductions, oxidations, and other phase I reactions. We were able to identify the previously described congeners BTX-3 and BTX-B5, and tentatively identified BTX-9, 41,43-dihydro-BTX-2, several A-ring hydrolysis products, as well as several novel metabolites. Our results confirmed that fish are capable of similar BTX biotransformation reactions as reported for shellfish and mammals, but comparison of metabolite formation across the tested species suggested considerable interspecific variation in BTX-2 metabolism potentially leading to divergent BTX profiles. We additionally observed non-enzymatic formation of BTX-2 and BTX-3 glutathione conjugates. Collectively, these findings have important implications for determining the ecotoxicological fate of BTX in marine food webs.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Toxicon: X
Toxicon: X Pharmacology, Toxicology and Pharmaceutics-Toxicology
CiteScore
6.50
自引率
0.00%
发文量
33
审稿时长
14 weeks
期刊最新文献
Stress levels, hematological condition, and productivity of plasma-producing horses used for snake antivenom manufacture: A comparison of two industrial bleeding methods Diagnosis of human envenoming by terrestrial venomous animals: Routine, advances, and perspectives Supplementation of polyclonal antibodies, developed against epitope-string toxin-specific peptide immunogens, to commercial polyvalent antivenom, shows improved neutralization of Indian Big Four and Naja kaouthia snake venoms Bioprospection of rattlesnake venom peptide fractions with anti-adipose and anti-insulin resistance activity in vitro A probabilistic hazard assessment for cyanobacterial toxins accounting for regional geography and water body trophic status
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1