Rajan K Tripathy, Prakash Y Khandave, Janek Bzdrenga, Florian Nachon, Xavier Brazzolotto, Abhay H Pande
{"title":"Role of paraoxonase 1 in organophosphate G-series nerve agent poisoning and future therapeutic strategies.","authors":"Rajan K Tripathy, Prakash Y Khandave, Janek Bzdrenga, Florian Nachon, Xavier Brazzolotto, Abhay H Pande","doi":"10.1007/s00204-024-03884-2","DOIUrl":null,"url":null,"abstract":"<p><p>Chemical warfare nerve agents (CWNA) are neurotoxic chemicals unethically used as agents of mass destruction by terrorist outfits and during war. The available antidote against CWNA-mediated toxicity is not sufficiently effective and possesses several limitations. As a countermeasure, paraoxonase 1 (PON1), a catalytic bioscavenger, is being developed as a prophylactic treatment. However, the catalytic activity and substrate specificity of human PON1 are insufficient to be used as a potential antidote. Several laboratories have made different approaches to enhance the CWNA hydrolytic activity against various nerve agents. This review explores the holistic view of PON1 as a potential prophylactic agent against G-series CWNA poisoning, from its initial development to recent advancements and limitations. Apart from this, the review also provides an overview of all available PON1 variants that could be used as a potential prophylactic agent and discusses several possible ways to counteract immunogenicity.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":" ","pages":""},"PeriodicalIF":4.8000,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of Toxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00204-024-03884-2","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"TOXICOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Chemical warfare nerve agents (CWNA) are neurotoxic chemicals unethically used as agents of mass destruction by terrorist outfits and during war. The available antidote against CWNA-mediated toxicity is not sufficiently effective and possesses several limitations. As a countermeasure, paraoxonase 1 (PON1), a catalytic bioscavenger, is being developed as a prophylactic treatment. However, the catalytic activity and substrate specificity of human PON1 are insufficient to be used as a potential antidote. Several laboratories have made different approaches to enhance the CWNA hydrolytic activity against various nerve agents. This review explores the holistic view of PON1 as a potential prophylactic agent against G-series CWNA poisoning, from its initial development to recent advancements and limitations. Apart from this, the review also provides an overview of all available PON1 variants that could be used as a potential prophylactic agent and discusses several possible ways to counteract immunogenicity.
期刊介绍：
Archives of Toxicology provides up-to-date information on the latest advances in toxicology. The journal places particular emphasis on studies relating to defined effects of chemicals and mechanisms of toxicity, including toxic activities at the molecular level, in humans and experimental animals. Coverage includes new insights into analysis and toxicokinetics and into forensic toxicology. Review articles of general interest to toxicologists are an additional important feature of the journal.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
