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雏鸡的有机磷多发性神经病

Organophosphate polyneuropathy in chicks.

作者信息

Peraica M, Capodicasa E, Moretto A, Lotti M

机构信息

Università delgi Studi di Padova, Istituto di Medicina del Lavoro, Italy.

出版信息

Biochem Pharmacol. 1993 Jan 7;45(1):131-5. doi: 10.1016/0006-2952(93)90385-a.

Abstract

Young animals are resistant to organophosphate-induced delayed neuropathy (OPIDP), although biochemical changes on Neuropathy Target Esterase (NTE) caused by neuropathic organophosphorus esters (OP) are similar to those observed in the sensitive hen. We report here that the resistance of chicks to single doses of neuropathic OPs is not absolute because ataxia was produced in 40-day-old chicks by 2,2-dichlorovinyl dibutyl phosphate (DBDCVP, 5.0 or 10.0 mg/kg s.c.) and by diisopropyl phosphorofluoridate (DFP, 2.0 mg/kg s.c.). However, the clinical picture was different from that usually seen in hens; spasticity and complete recovery being the main features. alpha-Tolyl sulphonyl fluoride (PMSF, 300 mg/kg s.c.) promoted both DBDCVP neuropathy (5.0 or 10.0 mg/kg s.c.) and non-neuropathic doses of DFP (1.5 mg/kg s.c.) or DBDCVP (1.0 mg/kg s.c.). The lowest promoting dose of PMSF given 24 hr after 1.5 mg/kg of DFP was 30 mg/kg. Higher doses had a more severe effect but no further increase of OPIDP severity was obtained with doses ranging from 90 to 300 mg/kg. PMSF (30 mg/kg) protected 40-day-old chicks from subsequent doses of neuropathic OPs even when a promoting dose of PMSF followed. At 60 days of age, chicks' resistance to OPIDP decreased because lower doses of neuropathic OPs became effective and, similarly to hens, PMSF did not fully protect from subsequent promotion. In 40-day-old chicks the threshold of NTE inhibition for OPIDP development was 95-97% (DBDCVP 5.0 mg/kg). When promotion followed initiation, the minimal effective inhibition of NTE for initiation by neuropathic OPs was about 90%. In 36-day-old chicks, PMSF (300 mg/kg) promoted OPIDP when given up to 5 days after DFP (1.5 mg/kg) when residual NTE inhibition in brain and sciatic nerve was about 40%. We conclude that chicks' resistance to OPIDP might reflect either a less effective initiation by phosphorylated NTE or a more efficient repair mechanism or both, and also that promotion is likely to involve a target other than NTE.

摘要

幼龄动物对有机磷酸酯诱导的迟发性神经病(OPIDP)具有抗性,尽管神经性有机磷酯(OP)引起的神经病靶酯酶(NTE)的生化变化与在敏感母鸡中观察到的相似。我们在此报告,雏鸡对单剂量神经性OP的抗性并非绝对,因为2,2 - 二氯乙烯基二丁基磷酸酯(DBDCVP,5.0或10.0 mg/kg皮下注射)和二异丙基氟磷酸酯(DFP,2.0 mg/kg皮下注射)可使40日龄雏鸡产生共济失调。然而,临床症状与通常在母鸡中看到的不同;痉挛和完全恢复是主要特征。α-甲苯磺酰氟(PMSF,300 mg/kg皮下注射)可促进DBDCVP神经病(5.0或10.0 mg/kg皮下注射)以及非神经性剂量的DFP(1.5 mg/kg皮下注射)或DBDCVP(1.0 mg/kg皮下注射)。在1.5 mg/kg DFP给药24小时后给予的PMSF的最低促进剂量为30 mg/kg。更高剂量的效果更严重,但在90至300 mg/kg范围内的剂量并未使OPIDP严重程度进一步增加。PMSF(30 mg/kg)可保护40日龄雏鸡免受后续剂量的神经性OP的影响,即使随后给予促进剂量的PMSF也是如此。在60日龄时,雏鸡对OPIDP的抗性降低,因为较低剂量的神经性OP变得有效,并且与母鸡一样,PMSF不能完全保护其免受后续促进作用。在40日龄雏鸡中,OPIDP发生的NTE抑制阈值为95 - 97%(DBDCVP 5.0 mg/kg)。当促进作用在引发之后发生时,神经性OP引发的NTE的最小有效抑制约为90%。在36日龄雏鸡中,当在DFP(1.5 mg/kg)给药后长达5天给予PMSF(300 mg/kg)时,脑和坐骨神经中的残余NTE抑制约为40%,此时PMSF可促进OPIDP。我们得出结论,雏鸡对OPIDP的抗性可能反映了磷酸化NTE引发作用效率较低或修复机制更有效或两者兼而有之,并且促进作用可能涉及NTE以外的靶点。

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