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Phenylmethylsulfonyl fluoride protects rats from Mipafox-induced delayed neuropathy.

Publication ,  Journal Article
Veronesi, B; Padilla, S
Published in: Toxicology and applied pharmacology
November 1985

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, we report that prior exposure to a nonaging 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 (250 mg/kg, sc) or to Mipafox (15 mg/kg, ip) and a time course of brain NTE inhibition and recovery was defined. A separate group of PMSF-treated rats was exposed to Mipafox when brain NTE inhibition was 87.7 +/- 2.3%. Conversely, another group of rats, pretreated with Mipafox, was dosed with PMSF when NTE inhibition was 90.2 +/- 0.8%. A third group of animals, treated with PMSF, was exposed to Mipafox 14 days later, when NTE activity had recovered to within 10 +/- 4.2% of control amounts. Histopathological survey (14 to 21 days post-exposure) indicated severe cervical cord damage (damage score greater than or equal to 3) in the following frequencies: PMSF, 0%; Mipafox, 85%; PMSF-4 hr-Mipafox, 0%; Mipafox-4 hr-PMSF, 100%; PMSF-14 days-Mipafox, 75%; controls, 0%. These data indicate that PMSF pretreatment protects rats against Mipafox-induced neurological damage and that the timing of administration and order of presentation are critical to this protection. These results support the hypothesis that the initiation of OPIDN is a multistage event involving inhibition and aging, and these stages are experimentally separable.

Duke Scholars

Published In

Toxicology and applied pharmacology

DOI

EISSN

1096-0333

ISSN

0041-008X

Publication Date

November 1985

Volume

81

Issue

2

Start / End Page

258 / 264

Related Subject Headings

  • Toxicology
  • Sulfones
  • Spinal Cord
  • Rats
  • Phenylmethylsulfonyl Fluoride
  • Nervous System Diseases
  • Male
  • Isoflurophate
  • Injections, Subcutaneous
  • Injections, Intraperitoneal
 

Citation

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Veronesi, B., & Padilla, S. (1985). Phenylmethylsulfonyl fluoride protects rats from Mipafox-induced delayed neuropathy. Toxicology and Applied Pharmacology, 81(2), 258–264. https://doi.org/10.1016/0041-008x(85)90162-0
Veronesi, B., and S. Padilla. “Phenylmethylsulfonyl fluoride protects rats from Mipafox-induced delayed neuropathy.Toxicology and Applied Pharmacology 81, no. 2 (November 1985): 258–64. https://doi.org/10.1016/0041-008x(85)90162-0.
Veronesi B, Padilla S. Phenylmethylsulfonyl fluoride protects rats from Mipafox-induced delayed neuropathy. Toxicology and applied pharmacology. 1985 Nov;81(2):258–64.
Veronesi, B., and S. Padilla. “Phenylmethylsulfonyl fluoride protects rats from Mipafox-induced delayed neuropathy.Toxicology and Applied Pharmacology, vol. 81, no. 2, Nov. 1985, pp. 258–64. Epmc, doi:10.1016/0041-008x(85)90162-0.
Veronesi B, Padilla S. Phenylmethylsulfonyl fluoride protects rats from Mipafox-induced delayed neuropathy. Toxicology and applied pharmacology. 1985 Nov;81(2):258–264.
Journal cover image

Published In

Toxicology and applied pharmacology

DOI

EISSN

1096-0333

ISSN

0041-008X

Publication Date

November 1985

Volume

81

Issue

2

Start / End Page

258 / 264

Related Subject Headings

  • Toxicology
  • Sulfones
  • Spinal Cord
  • Rats
  • Phenylmethylsulfonyl Fluoride
  • Nervous System Diseases
  • Male
  • Isoflurophate
  • Injections, Subcutaneous
  • Injections, Intraperitoneal