Relationship of Neuropathy Target Esterase Inhibition to Neuropathology andAtaxia in Hens Given Organophosphorus Esters

摘要

Adult White Leghorn hens were acutely exposed to 3 dosages of the followingorganophosphorus compounds: mipafox, tri-ortho-tolyl phosphate (TOTP), phenyl saligenin phosphate, and diisopropylphosphorofluoridate (DFP). Neuropathy target esterase (NTE) activity was measured in brain and spinal cord 4 or 48 h after exposure. Ataxia was assessed using an 8-point rating scale on days 9 through 21 after administration, and neuropathological examination was conducted on samples collected from perfusion-fixed animals on day 21. Morphological alterations were indicated by lesion scores between 0 (no lesions) and 4 (diffuse involvement of spinal cord tracts and > 25% degeneration of peripheral nerve fibers). Dosages of mipafox, TOTP, phenyl saligenin phosphate, and DFP that were capable of inhibiting NTE > 80% in both brain and spinal cord preceded ataxia which reached maximal levels (scores of 7-8), and development of lesions scored as 4. Hens were notably impaired (ataxia scores of 3-4) 21 days after administration of dosages of mipafox, TOTP, phenyl saligenin phosphate, and DFP when spinal cord NTE was inhibited 40-75%. Lesions were, however, only noted in spinal cord and peripheral nerves of hens given TOTP or DFP (scores 1-3).