title: Paraoxon toxicity is not potentiated by prior reduction in blood acetylcholinesterase.
abstract: 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.
authors.affiliation: Neurotoxicology Division (MD-74B), U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
authors.forename: S
authors.initials: S
authors.lastname: Padilla
authors.forename: V C
authors.initials: VC
authors.lastname: Moser
authors.forename: C N
authors.initials: CN
authors.lastname: Pope
authors.forename: W S
authors.initials: WS
authors.lastname: Brimijoin
mesh_terms: 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
chemical_list: D000911:Antibodies, Monoclonal; D000110:Acetylcholinesterase; D010261:Paraoxon