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Phenylmethylsulfonyl fluoride alters sensitivity to organophosphorus-induced delayed neurotoxicity in developing animals.

Publication ,  Journal Article
Pope, CN; Chapman, ML; Tanaka, D; Padilla, S
Published in: Neurotoxicology
January 1992

The serine/cysteine hydrolase inhibitor phenylmethylsulfonyl fluoride (PMSF) markedly intensifies the clinical expression of organophosphorus-induced delayed neurotoxicity (OPIDN) in adult chickens when administered after organophosphate exposure. In this study, we have examined the ability of PMSF post-treatment to affect sensitivity to OPIDN in developing animals at ages normally showing resistance. Chickens (35, 49 or 70 days of age) were treated with diisopropylphosphorofluoridate (DFP, 2 mg/kg, sc) and then treated four hours later with PMSF (90 mg/kg, sc) or vehicle only and examined for clinical signs of ataxia and incoordination. Chickens treated with DFP alone showed a marked age-related increase in the severity of motor deficits. Birds treated with DFP followed by PMSF showed more extensive clinical deficits relative to those treated with DFP only, but relatively similar degrees of motor dysfunction among the age groups. Cervical spinal cord samples processed by the Fink-Heimer degeneration method indicated that PMSF post-treatment induced more extensive axonal degeneration in all age groups relative to treatment with DFP only. As the DFP treatment alone caused greater than or equal to 90% inhibition of neurotoxic esterase activity (NTE, the putative molecular target site for OPIDN), interaction with NTE by PMSF does not appear to be involved in potentiation. We hypothesize that PMSF potentiates OPIDN through impairment of a physiological process which normally imparts resistance to young animals and which regresses during development.

Duke Scholars

Published In

Neurotoxicology

EISSN

1872-9711

ISSN

0161-813X

Publication Date

January 1992

Volume

13

Issue

2

Start / End Page

355 / 364

Related Subject Headings

  • Toxicology
  • Time Factors
  • Spinal Cord
  • Reaction Time
  • Phenylmethylsulfonyl Fluoride
  • Organophosphorus Compounds
  • Nervous System
  • Nerve Degeneration
  • Isoflurophate
  • Female
 

Citation

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MLA
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Pope, C. N., Chapman, M. L., Tanaka, D., & Padilla, S. (1992). Phenylmethylsulfonyl fluoride alters sensitivity to organophosphorus-induced delayed neurotoxicity in developing animals. Neurotoxicology, 13(2), 355–364.
Pope, C. N., M. L. Chapman, D. Tanaka, and S. Padilla. “Phenylmethylsulfonyl fluoride alters sensitivity to organophosphorus-induced delayed neurotoxicity in developing animals.Neurotoxicology 13, no. 2 (January 1992): 355–64.
Pope CN, Chapman ML, Tanaka D, Padilla S. Phenylmethylsulfonyl fluoride alters sensitivity to organophosphorus-induced delayed neurotoxicity in developing animals. Neurotoxicology. 1992 Jan;13(2):355–64.
Pope, C. N., et al. “Phenylmethylsulfonyl fluoride alters sensitivity to organophosphorus-induced delayed neurotoxicity in developing animals.Neurotoxicology, vol. 13, no. 2, Jan. 1992, pp. 355–64.
Pope CN, Chapman ML, Tanaka D, Padilla S. Phenylmethylsulfonyl fluoride alters sensitivity to organophosphorus-induced delayed neurotoxicity in developing animals. Neurotoxicology. 1992 Jan;13(2):355–364.
Journal cover image

Published In

Neurotoxicology

EISSN

1872-9711

ISSN

0161-813X

Publication Date

January 1992

Volume

13

Issue

2

Start / End Page

355 / 364

Related Subject Headings

  • Toxicology
  • Time Factors
  • Spinal Cord
  • Reaction Time
  • Phenylmethylsulfonyl Fluoride
  • Organophosphorus Compounds
  • Nervous System
  • Nerve Degeneration
  • Isoflurophate
  • Female