Role of paraoxonase 1 in organophosphate G-series nerve agent poisoning and future therapeutic strategies

• Published in: Archives of toxicology 2024-10
• Main Authors: Tripathy, Rajan K, Khandave, Prakash Y, Bzdrenga, Janek, Nachon, Florian, Brazzolotto, Xavier, Pande, Abhay H
• Format: Article
• Language: English
• ISSN: 0340-5761; 1432-0738; 1432-0738
• DOI: 10.1007/s00204-024-03884-2

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.