In Vivo Cholinesterase Inhibitory Specificity of Organophosphorus Nerve Agents
Abstract
The purpose of this project was to determine and compare the time-related changes in blood, brain, and tissue acetylcholinesterase (AChE) activity during the first hour after exposure to six organophosphorus nerve agents (GA, GB, GD, GF, VR, and VX) in Hartley guinea pigs. Animals were pretreated with atropine methyl nitrate (l% .0 mg/kg, i.m.) to minimize peripheral toxic effects 15 min before they were given a 1.0 x LD50 subcutaneous dose of a nerve agent. At 0,5, 10, 15,30, and 6Omin after nerve agent, animals were humanely euthanized. Blood was collected and brain regions (brainstem, cortex, hippocampus, midbrain, cerebellum, striatum, and spinal cord) and peripheral tissues (diaphragm, skeletal muscle, and heart) were dissected and processed for AChE activity. All six nerve agents produced maximum inhibition of AChE in red blood cells between 5 and 10% of the control within lOmin after exposure. In whole blood, differential effects were observed among the agents: GB, GD, and GF produced more rapid and greater inhibition than did GA, VR, and Vx. GF was the most rapid, producing a maximum inhibition to 5% of the control in 5 min. while VR and VX were slower reaching maximum inhibition to 30% of the control at 15 min. The enzyme actiyity in the majority of the brain regions was more markedly inhibited by the G-agents than by the V-agents. The G-agents caused rapid AChE inhibition, reaching maximum levels (20-30% of control) at 15 min and GA produced the most rapid effects. V-agents produced much slower and less AChE inhibition, reaching maximum (35-60% of control) at 30 min. In the diaphragm, VR, VX, and GD produced more rapid and greater AChE inhibition than other G-agents; GA produced the slowest and least inhibition. In the skeletal muscle, VX induced the most rapid and severe inhibition, while GA the least inhibition. In the heart, all agents produced very rapid inhibition, and GD produced the most severe inhibition of AChE activity.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 26, 2005
- Accession Number
- ADA468835
Entities
People
- John H. McDonough
- Robert K. Kan
- Tsung-Ming Shih
Organizations
- United States Army Medical Research Institute of Chemical Defense