Effect of prevention and potentiation of diisopropyl phosphorofluoridate (DFP)-induced delayed neurotoxicity on the mRNA expression of neurofilament subunits in hen central nervous system.

Abstract

Diisopropyl phosphorofluoridate (DFP) is an organophosphorus ester, which produces mild ataxia in 7-14 days and severe ataxia or paralysis in about 20 days (OPIDN) in hens. Previous studies in this laboratory have shown enhanced temporal expression of neurofilament (NF) subunit mRNAs in the spinal cord (SC) of DFP-treated hens. The main objective of this investigation was to study the effect of DFP administration on NF subunit mRNAs expression, when OPIDN is protected or potentiated by pre-treatment or post-treatment, respectively, with phenylmethylsulfonyl fluoride (PMSF). The hens were sacrificed 1, 5, 10, and 20 days after the last treatment. In contrast with enhanced mRNA expression of NF subunits reported in OPIDN, there was no alteration in the expression of NF subunits in the SC of PMSF-protected hens that did not develop OPIDN. PMSF post-treatment of DFP-treated hens, which enhanced delayed neurotoxicity produced by a low dose of DFP, exhibited decrease in the mRNA expression of NF subunits in SC at all time periods (1-20 days) of observation. The expression of NF subunits was also studied in the degeneration-resistant tissue cerebrum of treated hens. The results from protected hens suggested that temporal enhanced expression of NF subunit mRNAs in DFP-treated hens might be contributing to the development of OPIDN in hens. By contrast, PMSF post-treatment seemed to potentiate OPIDN by a mechanism different from that followed by DFP alone to produce OPIDN.

• Authors: K Xie, R P Gupta, M B Abou-Donia
• Journal: Biochemistry and cell biology = Biochimie et biologie cellulaire (Biochem Cell Biol) Vol. 79 Issue 2 Pg. 207-17 ( 2001) ISSN: 0829-8211 [Print] Canada
• PMID: 11310568 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Neurofilament Proteins
• Protein Subunits
• RNA, Messenger
• Isoflurophate
• Phenylmethylsulfonyl Fluoride

Topics

• Animals
• Central Nervous System (metabolism)
• Central Nervous System Diseases (chemically induced, physiopathology)
• Chickens
• Gene Expression (drug effects)
• Isoflurophate (toxicity)
• Neurofilament Proteins (biosynthesis, genetics)
• Phenylmethylsulfonyl Fluoride (pharmacology)
• Protein Subunits
• RNA, Messenger (analysis, drug effects)
• Spinal Cord (drug effects, metabolism)
• Telencephalon (drug effects, metabolism)