Despite six decades of extensive research in medical countermeasures against
nerve agent poisoning, a broad spectrum
acetylcholinesterase (AChE) reactivator is not yet available. One current approach is directed toward synthesizing
oximes with high affinity and reactivatability toward
butyrylcholinesterase (BChE) in plasma to generate an effective pseudocatalytic scavenger. An interim
solution could be the administration of external AChE or BChE from blood products to augment pseudocatalytic scavenging with slower but clinically approved
oximes to decrease
nerve agent concentrations in the body. We here semiquantitatively investigate the ability of
obidoxime and
HI-6 to decrease the inhibitory activity of
VX with human AChE and BChE from whole blood, erythrocyte membranes, erythrocytes, plasma, clinically available fresh frozen plasma and packed red blood cells. The main findings are that whole blood showed a
VX concentration-dependent decrease in inhibitory activity with
HI-6 being more potent than
obidoxime. Using erythrocytes and erythrocyte membranes again,
HI-6 was more potent compared to
obidoxime. With freshly prepared plasma,
obidoxime and
HI-6 showed comparable results for the decrease in
VX. The use of the clinically available blood products revealed that packed red blood cells showed similar kinetics as fresh erythrocytes. Fresh frozen plasma resulted in a slower and incomplete decrease in inhibitory plasma compared to freshly prepared plasma. In conclusion, the administration of blood products in combination with available
oximes augments pseudocatalytic scavenging and might be useful to decrease the body load of persistent, highly toxic
nerve agents.