Phosphine-induced human erythrocyte cholinesterase inhibition is reactivable by oximes: A step towards antidote development for phosphine.

Phosphine-releasing metal phosphides are used to protect stored grains. Phosphine gas can be fatal if inhaled. However, the easy availability of metal phosphides (like Aluminium phosphide) causes increased misuse to commit suicide. Phosphine is a mitochondrial poison and affects the body's major organs. Phosphine poisoning has no specific diagnostic biomarker or remedy/antidote. It is reported that phosphine inhibits erythrocyte cholinesterase activity. However, contradictory views regarding this issue exist, and no consensus has been reached yet. Further, it is completely unknown that even if phosphine inhibits erythrocyte cholinesterase activity, such inhibition is reactivated by standard oxime reactivators akin to organophosphorus pesticide-induced enzyme inhibition. Keeping in mind that there is no antidote to phosphine exposure, it is important to solve the reactivation issue in the context of phosphine-induced enzyme inhibition. The in-silico (molecular docking and molecular dynamics simulation studies) and in-vitro (electrophoretic and spectroscopic) studies were carried out to understand the effect of phosphine exposure on erythrocyte cholinesterase activity. Besides the oximes used to understand the reactivation of the enzyme activity. From the results, it was discovered that phosphine inhibits human erythrocyte cholinesterase, akin to neostigmine and dichlorvos. Moreover, such inhibition is reactivated by oximes. It is concluded that erythrocyte cholinesterase activity holds significant promise as a biomarker for phosphine inhalation toxicity, and oximes may serve as a potential antidote.