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

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.