title: Protein levels of neurofilament subunits in the hen central nervous system following prevention and potentiation of diisopropyl phosphorofluoridate (DFP)-induced delayed neurotoxicity(1).
abstract: Diisopropyl phosphorofluoridate (DFP) is an organophosphorus ester, which produces delayed neurotoxicity (OPIDN) in hens in 7-14 days. OPIDN is characterized by mild ataxia in its initial stages and severe ataxia or paralysis in about 3 weeks. It is marked by distal swollen axons, and exhibits aggregations of neurofilaments (NFs), microtubules, proliferated smooth endoplasmic reticulum, and multivesicular bodies. These aggregations subsequently undergo disintegration, leaving empty varicosities. Previous studies in this laboratory have shown an increased level of medium-molecular weight NF (NF-M) and decreased levels of high- and low-molecular weight NF (NF-H, NF-L) proteins in the spinal cord of DFP-treated hens. The main objective of this investigation was to study the effect of DFP administration on NF subunit levels when OPIDN is prevented or potentiated by pretreatment or post-treatment with phenylmethylsulfonyl fluoride (PMSF), respectively. Hens pretreated or post-treated with PMSF were killed 1, 5, 10, and 20 days after the last treatment. The alteration in NF subunit protein levels observed in DFP-treated hen spinal cords was not observed in protected hens. Estimation of NFs in the potentiation experiments, however, showed a different pattern of alteration in NF subunit levels. The results showed that an alteration in NF subunit levels in DFP-treated hens might be related to the development of OPIDN, since these changes were suppressed in PMSF-protected hens. However, results from PMSF post-treated hen spinal cords suggested that potentiation of OPIDN by PMSF was mediated by a mechanism different from that followed by DFP alone to produce OPIDN.
authors.affiliation: Neurotoxicology Laboratory, School of Life Science, University of Science and Technology of China, 230027, Hefei, Anhui, P. R. China.
authors.forename: Keqin
authors.initials: K
authors.lastname: Xie
authors.forename: Ram P
authors.initials: RP
authors.lastname: Gupta
authors.forename: Mohamed B
authors.initials: MB
authors.lastname: Abou-Donia
mesh_terms: D000818:Animals; D002645:Chickens; D004347:Drug Interactions; D007531:Isoflurophate / Q000633:toxicity*; D016900:Neurofilament Proteins / Q000276:immunology / Q000378:metabolism*; D020258:Neurotoxicity Syndromes / Q000378:metabolism*; D010664:Phenylmethylsulfonyl Fluoride / Q000633:toxicity; D011480:Protease Inhibitors / Q000633:toxicity; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D013687:Telencephalon / Q000187:drug effects* / Q000378:metabolism
chemical_list: D016900:Neurofilament Proteins; D011480:Protease Inhibitors; C044882:neurofilament protein L; C051774:neurofilament protein H; C061195:neurofilament protein M; D007531:Isoflurophate; D010664:Phenylmethylsulfonyl Fluoride