Spectroelectrochemical testing of a proposed mechanism for a redox-based therapeutic intervention: Ascorbate treatment of severe paraquat poisoning

••Ascorbate has been proposed for severe paraquat poisoning.••Spectroelectrochemical studies indicate ascorbate cannot quench the paraquat radical.••Oxidized ascorbate (e.g., dehydroascorbate) can quench the paraquat radical. The toxicity of paraquat is believed to involve a redox-cycling mechanism that can disrupt cellular redox homeostasis and, also, generate damaging free radicals. It has been suggested that for cases of severe paraquat poisoning the administration of ascorbate (i.e., vitamin C) can confer benefit by quenching the paraquat free radical (PQ+·). Here, we used an electrochemical approach that abstracts-away many of the (bio)chemical complexities and isolates the redox-interactions between paraquat and ascorbate. Specifically, we used a series of experiments that coupled electrochemical measurements of electron flow with optical measurements of paraquat's redox-state switching. Our results demonstrate that the reduced absorbate cannot quench the PQ+·-radical because they are both reductants. However, oxidation of ascorbate does allow PQ+·-radical scavenging. More broadly, we believe this study demonstrates the potential for developing electrochemical approaches to complement existing experimental methods in redox biology. [Display omitted]