Neurofilaments degradation as an early molecular event in tri-ortho-cresyl phosphate (TOCP) induced delayed neuropathy.
Tri-ortho-cresyl phosphate (TOCP), an organophosphorus ester, is capable of producing organophosphorus ester-induced delayed neuropathy (OPIDN) in human being and sensitive animals. In the present study, adult hens were treated with TOCP by gavage at single dosage of 750 mg/kg, and sacrificed by decapitation on the corresponding time points of 1, 5, 10, and 21 day post-dosing, respectively. The tibial nerves were dissected, homogenized, and centrifuged at 100,000 xg. The level of neurofilaments protein in both pellet and supernatant fractions was determined. Western blot analysis showed a nearly depletion of NF-M and a dramatic decrease of NF-L in both fractions of tibial nerves. These changes were observed within 24h of TOCP administration and then followed by an obvious recovery. In contrast, a progressive reduction in NF-H was observed in tibial nerves of TCOP-treated hens throughout the period of experiment. With the reduction of NF-L level, the rate of NF-L degradation demonstrated a significant increase in both fractions of tibial nerves. Furthermore, the expression of mu-calpain in tibial nerves was increased following TOCP. Taken together, these results demonstrated that NFs changes occurred much earlier than the clinical appearance of ataxia in TOCP-induced delayed neuropathy, indicating that disruption of NF homeostasis in peripheral nerves might be an early molecular event in the development of OPIDN.
Institute of Toxicology, Shandong University, Jinan, Shandong 250012, People's Republic of China.
Fuyong
F
Song
Yongjian
Y
Yan
Xiulan
X
Zhao
Cuili
C
Zhang
Keqin
K
Xie
D000284:Administration, Oral; D000818:Animals; D002645:Chickens / Q000378:metabolism; D005260:Female; D007700:Kinetics; D016900:Neurofilament Proteins / Q000187:drug effects* / Q000378:metabolism; D020258:Neurotoxicity Syndromes / Q000378:metabolism*; D010525:Peripheral Nerves / Q000187:drug effects* / Q000378:metabolism; D011115:Polyneuropathies / Q000378:metabolism*; D013979:Tibial Nerve / Q000187:drug effects / Q000378:metabolism; D014317:Tritolyl Phosphates / Q000008:administration & dosage / Q000633:toxicity*
D016900:Neurofilament Proteins; D014317:Tritolyl Phosphates