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.
Song
Fuyong
F
Institute of Toxicology, Shandong University, Jinan, Shandong 250012, People's Republic of China.
Yan
Yongjian
Y
Zhao
Xiulan
X
Zhang
Cuili
C
Xie
Keqin
K
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