Relationship of neuropathy target esterase inhibition to neuropathology and ataxia in hens given organophosphorus esters.
Adult White Leghorn hens were acutely exposed to 3 dosages of the following organophosphorus 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 (30 mg/kg i.p.), TOTP (500 mg/kg p.o.), phenyl saligenin phosphate (2.5 mg/kg i.m.) and DFP (1 mg/kg s.c.) 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 (3 and 6 mg/kg), TOTP (90 mg/kg), phenyl saligenin phosphate (0.1 and 0.2 mg/kg), and DFP (0.4 mg/kg) 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). These data indicate that inhibition of spinal cord NTE > 80% was predictive of severe ataxia and extensive pathology in the hen and that less NTE inhibition was indicative of less severe ataxia and a lower score for neuropathological damage.
Ehrich
M
M
Virginia-Maryland Regional College of Veterinary Medicine, Blacksburg 24061.
Jortner
B S
BS
Padilla
S
S
D000818:Animals; D001259:Ataxia / Q000139:chemically induced / Q000201:enzymology*; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors*; D002645:Chickens; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D009422:Nervous System Diseases / Q000139:chemically induced / Q000201:enzymology*; D009943:Organophosphorus Compounds / Q000633:toxicity*; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology / Q000473:pathology
D009943:Organophosphorus Compounds; D002265:Carboxylic Ester Hydrolases; C021859:neurotoxic esterase