Organophosphate-induced inhibition of acetylcholinesterase, oxidative stress and neuroinflammation

Abstract

Organophosphate (OP) neurotoxicants exert their toxicity by inhibiting acetylcholinesterase. Overstimulation of cholinergic receptors can rapidly lead to neuronal damage, seizures, death, and long-term neurological damage in survivors. This review summarizes the mechanisms by which OP agents inhibit acetylcholinesterase action and lead to pathological acetylcholine overload in vivo, with attention to the effects of chronic and low-dose toxicity. Importantly, the massive accumulation of ROS during oxidative stress caused by OP agents are found to widely present in all toxic reactions. Moreover, OP agents can cause the release of pro-inflammatory cytokines from astrocytes, microglia, and increase the levels of prostaglandins and is prostaglandins, leading to neuroinflammation. A comprehensive understanding of the mechanisms of op-agents could help develop rational therapeutic approaches to treat toxicant exposure. However, current treatment for organophosphorus agent poisoning is relatively limited. Further research on the mechanisms of neurotoxicity is required to find ways to detoxify and treat organophosphorus agents.