Proposing an antidote for poisonous phosphine in view of mitochondrial electrochemistry facts

Abstract

Metal phosphides in general are potent pesticides that are a common cause of human poisoning. Various salts of phosphides produce highly toxic phosphine in exposure to gastric acid that results in multi-organ damage and death. There is no antidote for phosphine poisoning and most of human poisoned cases do not survive. All we know so far is that phosphine is a mitochondrial toxin that inhibits cellular respiration and induces oxidative stress. Mechanistically, phosphine as a reducing agent interacts with metal ion cofactors at the active site of enzymes and inhibits key enzymes such as cytochrome C oxidase that lead to inhibition of mitochondrial respiration. Phosphine (E0 = −1.18 V) as a reducing agent gives electrons to cytochrome C oxidase (E0 = +0.29 V). Metal phosphides with lower reduction potential are stronger electron donors and thus stronger poisons. Our hypothesis is that if an electron receiver stronger than cytochrome C oxidase is used then it would compete with cytochrome C oxidase in interaction with phosphine. This competition might prevent or reduce the inhibition of cellular respiration. This idea can be tested in an animal model of phosphine toxicity by monitoring cardiovascular state and measuring the cardiac mitochondrial function.