Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jan 18;14(1):tfae223.
doi: 10.1093/toxres/tfae223. eCollection 2025 Feb.

N-acetylcysteine prevents cholinergic and non-cholinergic toxic effects induced by nerve agent poisoning in rats

Poorna Shri  1 , K P Singh  1 , Varsha Rani  1 , D P Nagar  1 , J Acharya  2 , A S B Bhaskar  1
Affiliations

N-acetylcysteine prevents cholinergic and non-cholinergic toxic effects induced by nerve agent poisoning in rats

Poorna Shri et al. Toxicol Res (Camb). .

Abstract

Objective: Organophosphorus Nerve Agent, VX [(O-Ethyl S-diisopropylaminomethyl) methylphosphonothioate] compound interferes with acetylcholine signaling by targeting the AChE enzyme. Studies suggest that in nerve agents poisoning, non-cholinergic effects are also responsible for damage in peripheral tissues including long term damage in brain. Present study reports cholinergic and non-cholinergic effects of VX poisoning and their prevention by use of N-acetylcysteine (NAC) in addition to conventional antidotes atropine sulphate and 2-PAM chloride as an antioxidant. NAC was chosen being an approved drug for medical conditions including oxidative damage and as mucolytic.

Results: Results of the study showed that after 1x LD 50 exposure to VX and standard atropine and oxime therapy resulted in recovery of cholinesterase activity up to 51%, while additional NAC administration resulted in increased recovery up to 89% in brain cholinesterase activity. NAC also helped in maintaining intracellular and tissue GSH level, reduced ROS generation and lipid peroxidation. NAC treatment could able to reduce the lipid peroxidation (MDA) levels in liver of NAC administered groups as compared to standard treatment of atropine sulphate and PAM chloride at 10 LD 50 VX. Likewise, a 20% higher level of GSH was found in NAC treated group at 1x LD 50 dose in brain. Cell cycle analysis and histopathological results showed that NAC prevents VX induced damage.

Conclusion: it was found that use of antioxidant agent NAC along with standard atropine-oxime treatment is helpful in reducing the cholinergic and oxidative stress mediated toxicity induced by VX.

Keywords: antidotes; cholinergic crisis; nac; nerve agents; non-cholinergic.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

References

    1. Costa LG. Organophosphorus compounds at 80: some old and new issues. Toxicol Sci. 2018:162(1):24–35. - PMC - PubMed
    1. Hung D-Z, Yang H-J, Li Y-F, Lin C-L, Chang S-Y. The long-term effects of organophosphates poisoning as a risk factor of CVDs: a Nationwide population-based cohort study. 2015:10(9):1–15. - PMC - PubMed
    1. Carey JL, Dunn C, Gaspari RJ. Central respiratory failure during acute organophosphate poisoning. Respir Physiol Neurobiol. 2013:189(2):403–410. - PubMed
    1. Aardema H, Meertens JHJM, Ligtenberg JJM. Organophosphorus pesticide poisoning: cases and developments, Netherlands. J Med Rev. 2008:66:149–153. - PubMed
    1. Pearson JN, Patel M. The role of oxidative stress in organophosphate and nerve agent toxicity. Ann N Y Acad Sci. 2016:1378(1):1–8. - PMC - PubMed

LinkOut - more resources