Paraoxon toxicity is not potentiated by prior reduction in blood acetylcholinesterase.
The role of blood acetylcholinesterase in moderating the effects of organophosphate challenge in rats was tested. Adult male rats (n = 42) were injected (iv) either with monoclonal antibodies (MAb) to rat acetylcholinesterase (EC 3.1.1.7; AChE) or normal mouse IgG (controls). Two days later, the rats were injected (sc) with either a mild (0.17 mg/kg) or moderate dosage (0.34 mg/kg) of paraoxon or with vehicle. Neurological integrity was assessed by a functional observational battery followed by motor activity, 3 to 4 hr after dosing. Blood, brain, and diaphragm tissues were then collected for determination of AChE activity. MAb treatment reduced whole blood and plasma AChE activity by 32 and 90%, respectively, but did not affect neurobehavioral parameters or the AChE activity of brain or diaphragm. The paraoxon challenge produced dose-related neurobehavioral changes and inhibition of brain and diaphragm AChE activity to the same extent in IgG- and MAb-treated rats. Thus, significant loss in blood AChE alone produced no detectable neurobehavioral deficits and did not alter the subsequent responses to paraoxon challenge.
Padilla
S
S
Neurotoxicology Division (MD-74B), U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
Moser
V C
VC
Pope
C N
CN
Brimijoin
W S
WS
D000110:Acetylcholinesterase / Q000097:blood* / Q000276:immunology / Q000502:physiology; D000818:Animals; D000911:Antibodies, Monoclonal; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000201:enzymology; D003964:Diaphragm / Q000201:enzymology; D004357:Drug Synergism; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010261:Paraoxon / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity
D000911:Antibodies, Monoclonal; D000110:Acetylcholinesterase; D010261:Paraoxon