Chinese Journal of Tissue Engineering Research ›› 2014, Vol. 18 ›› Issue (49): 7884-7890.doi: 10.3969/j.issn.2095-4344.2014.49.003

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Organophosphorus poisoning-induced delayed neuropathy hen model induced by triorthocresyl phosphate and phenylmethylsulfonyl fluoride intervention  

Zuo En-jun1, Piao Feng-yuan2, Jiang Ying3   

  1. 1College of Stomatology, Dalian Medical University, Dalian 116044, Liaoning Province, China;2Department of Occupational and Environmental Health, Dalian Medical University, Dalian 116044, Liaoning Province, China; 3Press of Journal, Dalian Medical University, Dalian 116044, Liaoning Province, China
  • Revised:2014-09-09 Online:2014-11-30 Published:2014-11-30
  • Contact: Jiang Ying, M.D., Lecturer, Press of Journal, Dalian Medical University, Dalian Medical University, Dalian 116044, Liaoning Province, China
  • About author:Zuo En-jun, Master, College of Stomatology, Dalian Medical University, Dalian 116044, Liaoning Province, China
  • Supported by:

     the National Natural Science Foundation of China, No. 81102160, 30771819

Abstract:

BACKGROUND: Although incidents of organophosphorus poisoning-induced delayed neuropathy (OPIDN) have been documented for over a century, the molecular mechanisms underlying the axonopathy remain poorly understood. Therefore, OPIDN treatment has been increasingly concerned.

OBJECTIVE: To construct the OPIDN hen model induced by triorthocresyl phosphate (TOCP) and to explore the effect of phenylmethylsulfonyl fluoride (PMSF) intervention.
METHODS: Adult hens were randomly divided into four groups: two TOCP groups, a PMSF group and a control group. TOCP groups were treated with TOCP by gavage at a single dosage of 1 000 mg/kg and 750 mg/kg respectively; control group was given an equivalent volume of saline by gavage while hens in the PMSF group were subcutaneously injected with 40 mg/kg PMSF 24 hours after 1 000 mg/kg TOCP injection. OPIDN neurological signs were assessed by a six-point graded scale. The changes of the hen weight were recorded. The hens were killed on day 5 and 21 post-dosing. The samples were cut into 50 nm thick sections and examined by transmission electron microscopy.
RESULTS AND CONCLUSION: OPIDN neurological signs such as abnormal gaits progressed in severity with time (P < 0.05), and the hen weight was significantly decreased in TOCP groups (P < 0.05). However, no clinical signs of delayed neurotoxicity were observed in hens of the PMSF group and the control group during the experiment period. The mild mitochondrial swelling and the fragmentation of microfilament and microtubule arrangement in axons were observed on day 5 post-dosing, leaving the other organelles remained unchanged. On day 21, neuronal degeneration was apparent, including swelling of endoplasmic reticulum, abnormal change of mitochondria, and disordered arrangement of cytoskeleton. The optimal dose of TOCP was 1 000 mg/kg. Experimental findings indicate that, OPIDN hen model induced by TOCP and PMSF intervention hen model were successfully constructed. PMSF intervention significantly improved the pathologic changes and clinical symptoms of OPIDN induced by TOCP in hens.


中国组织工程研究
杂志出版内容重点:肾移植肝移植移植;心脏移植;组织移植;皮肤移植;皮瓣移植;血管移植;器官移植组织工程


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Key words:  tissue engineering, organophosphorus compound, cytoskeleton, mitochondrion, endoplasmic reticulum

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