Central and peripheral neurotoxic esterase activity and dose-response relationship in adult hens after acute and chronic oral administration of diisopropyl fluorophosphate

• Published in: Ecotoxicology and environmental safety 1978-12, Vol.2 (3), p.383-399
• Main Authors: Olajos, E.J., DeCaprio, A.P., Rosenblum, I.
• Format: Article
• Language: English
• Subjects: Animals; Brain - enzymology; Chickens; Cholinesterases - metabolism; Dose-Response Relationship, Drug; Esterases - metabolism; Female; Isoflurophate - administration & dosage; Isoflurophate - toxicity; Nervous System Diseases - chemically induced; Nervous System Diseases - enzymology; Paraoxon - pharmacology; Sciatic Nerve - enzymology; Time Factors
• ISSN: 0147-6513; 1090-2414
• DOI: 10.1016/S0147-6513(78)80011-6

A number of organophosphates produce “delayed neurotoxicity” in man which may be modeled experimentally in several animal species such as the adult hen ( Gallus domesticus). Diisopropyl fluorophosphate (DFP) was selected as a typical neurotoxic agent. The development of delayed neurotoxicity was studied in adult White Leghorn hens after a single, oral dose (1.0 mg/kg) and after the administration of repeated low-level oral doses (125 μg/kg, 5 days/week; 1.0–5.0 mg/kg, total dose) of DFP. The relationship of dosage, time, and frequency of administration of subneurotoxic doses of DFP under conditions of a multiple-dose procedure was examined. Further, the comparative activities of hen brain and sciatic nerve neurotoxic esterase (NTE) was studied. The acute studies demonstrated that the percentage inhibition of NTE paralleled the increase in the degree of severity of the acute pharmacological response. The chronic dosing regimen resulted in a small, yet definite, inhibitory effect of DFP on brain NTE and cholinesterase activities. A maximum level of brain NTE inhibition occurred followed by a decrease and eventual levelling off of the inhibitory effect. The comparative NTE studies demonstrate that substrate hydrolysis by hen sciatic nerve preparations was considerably less when compared to hen brain extracts using equivalent weights of tissue. The results also demonstrated that the percentage of NTE of the total paraoxon-resistant activity was lower in sciatic nerve preparations compared to brain preparations. The effects of DFP on the NTE activities from brain and sciatic nerve preparations were definitely inhibitory and one may conclude that quantitative differences exist between NTE content and activity in peripheral and central nervous systems.