Long-term effects of human butyrylcholinesterase pretreatment followed by acute soman challenge in cynomolgus monkeys

Abstract

Human serum butyrylcholinesterase (Hu BChE) was demonstrated previously to be an effective prophylaxis that can protect animals from organophosphate nerve agents. However, in most of those studies, the maximum dose used to challenge animals was low (<2× LD 50), and the health of these animals was monitored for only up to 2 weeks. In this study, six cynomolgus monkeys received 75 mg of Hu BChE followed by sequential doses (1.5, 2.0, 2.0× LD 50) of soman 10 h later for a total challenge of 5.5× LD 50. Four surviving animals that did not show any signs of soman intoxication were transferred to WRAIR for the continuous evaluation of long-term health effects for 14 months. Each month, blood was drawn from these monkeys and analyzed for serum chemistry and hematology parameters, blood acetylcholinesterase (AChE) and BChE levels. Based on the serum chemistry and hematology parameters measured, no toxic effects or any organ malfunctions were observed up to 14 months following Hu BuChE protection against exposure to 5.5× LD 50 of soman. In conclusion, Hu BChE pretreatment not only effectively protects monkeys from soman-induced toxicity of the immediate acute phase but also for a long-term outcome.