||Potentiation of Organophosphorus-Induced Delayed Neurotoxicity by Phenylmethylsulfonyl Fluoride.
Pope, C. N. ;
Padilla, S. ;
||Health Effects Research Lab., Research Triangle Park, NC. Neurotoxicology Div. ;Northeast Louisiana Univ., Monroe. School of Pharmacy.
Nervous system ;
Organophosphorus compounds ;
Phenylmethylsulfonyl fluorides ;
Delayed hypersensitivity ;
Enzyme inhibitors ;
Organophosphorus induced delayed neurotoxicity(OPIDN)
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||It is well known that pretreatment with the serine esterase inhibitor phenylmethylsulfonyl fluoride (PMSF) can protect experimental animals from organophosphorus-induced delayed neurotoxicity (OPIDN), presumably by blocking the active site of neurotoxic esterase (NTE) such that binding and 'aging' of the neuropathic OP is thwarted. The authors report here that while PMSF (60 mg/kg, s.c.) given 4 hours before the neuropathic OP mipafox (50 mg/kg, i.m.) completely prevented the clinical expression of OPIDN in hens, the identical PMSF treatment markedly amplified the delayed neurotoxicity (relative to hens treated with the OP only) if administed 4 hours after mipafox (5 or 50 mg/kg, i.m.). Moreover, in a separate experiment using diisopropylphosphorofluoridate (DFP) as the neurotoxicant in place of mipafox, posttreatment with PMSF 4 hours after DFP (0.5 mg/kg) also accentuated the severity of the ataxia. These data indicate that PMSF only protects against OPIDN if given prior to exposure to the neurotoxicant; treatment with PMSF after OP exposure critically exacerbates the delayed neurotoxicity from exposure to organophosphorus compounds. (Copyright (c) 1990 by Hemisphere Publishing Corporation.)
||Pub. in Jnl. of Toxicology and Environmental Health, v31 n4 p261-273 Dec 90. Prepared in cooperation with Northeast Louisiana Univ., Monroe. School of Pharmacy.
|NTIS Title Notes
||Reprint: Potentiation of Organophosphorus-Induced Delayed Neurotoxicity by Phenylmethylsulfonyl Fluoride.
||57Y; 57Q; 57I
||PC A03/MF A01