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PHENYLMETHYLSULFONYL FLUORIDE PROTECTS RATS FROM MIPAFOX-INDUCED DELAYED NEUROPATHY
Citation:
Veronesi, B. AND S. Padilla. PHENYLMETHYLSULFONYL FLUORIDE PROTECTS RATS FROM MIPAFOX-INDUCED DELAYED NEUROPATHY. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-85/281 (NTIS PB86157971).
Description:
Initiation of organophosphorus-induced delayed neuropathy (OPIDN) is thought to consist of two molecular events involving the phosphorylation of the target enzyme, neurotoxic esterase or neuropathy target enzyme (NTE), and a subsequent 'aging' reaction which transforms the inhibited NTE into a charged moiety critical to the neuropathic process. Compounds that inhibit NTE but cannot age because of their chemical structure abort this two-stage initiation process, and when administered before a neurotoxic organophosphorus compound (OP), protect against the neuropathy by blocking NTE's active site (Johnson, 1970). In support of this, the authors report that prior exposure to a non-aging NTE inhibitor, phenylmethylsulfonyl fluoride (PMSF), protects rats from neurological damage after subsequent exposure to a neurotoxic OP, Mipafox. Adult, male Long Evans rats were exposed to either PMSF (250mg/kg, sc) or to Mipafox (15 mg/kg, ip) and a time-course of brain NTE inhibition and recovery was defined.