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新生大鼠幼崽的三乙基铅神经毒性:初步行为观察与量化

Neonatal triethyl lead neurotoxicity in rat pups: initial behavioral observations and quantification.

作者信息

Booze R M, Mactutus C F, Annau Z, Tilson H A

出版信息

Neurobehav Toxicol Teratol. 1983 May-Jun;5(3):367-75.

PMID:6877478
Abstract

Although alterations in development due to inorganic lead poisoning have been intensely investigated, little is known about the early toxicity of organic lead compounds. Assessment of developmental consequences due to triethyl lead (TEL) intoxication presently included (1) determination of the acute LD50 as 13 +/- 1 mg/kg, and (2) detailed examination of early neurobehavioral sequelae. The offspring of 12 Fischer-344 dams were administered on postpartum day 5 either a sham-injection, 15% ethanol, 3 mg/kg or 6 mg/kg TEL vis SC injection (20 microliters). Small, but significant, weight reductions of 6% and 13% for the 3- and 6- mg/kg TEL-dosed pups, respectively, were observed (days 14-30). Early sensory deficits of TEL pups as indicated by impaired olfactory discrimination on day 7 and decreased incidence of nipple attachment on day 9 were accompanied by the presence of fine whole body tremor (day 10). While these initial effects were transitory in nature, activity evaluations demonstrated persistent hypoactivity in high dose TEL males (days 15, 22, 24, 26, and 29). Passive avoidance acquisition was not affected by TEL treatment (day 18). However, 72 and 144 hr tests of passive avoidance retention (days 21 and 25) suggested alterations in affective behavior, i.e., hypoactivity in high dose TEL males and hyperactivity in low dose TEL females. A reduction in number, but not magnitude, of startle responses also occurred as a function of TEL exposure. The single postnatal day 5 injection of TEL thus produced transitory effects possibly reflecting direct TEL pharmacological activity, as well as apparent long-term effects suggesting potential permanent alterations in behavioral function.

摘要

尽管无机铅中毒对发育的影响已得到深入研究,但对于有机铅化合物的早期毒性却知之甚少。目前,对三乙铅(TEL)中毒发育后果的评估包括:(1)确定急性半数致死剂量(LD50)为13±1毫克/千克;(2)详细检查早期神经行为后遗症。12只Fischer-344母鼠的后代在产后第5天通过皮下注射(20微升)分别接受假注射、15%乙醇、3毫克/千克或6毫克/千克的TEL。在第14至30天观察到,接受3毫克/千克和6毫克/千克TEL剂量的幼崽体重分别显著减轻了6%和13%。TEL幼崽早期的感觉缺陷表现为第7天嗅觉辨别能力受损以及第9天乳头附着发生率降低,同时伴有全身细微震颤(第10天)。虽然这些初始影响本质上是暂时的,但活动评估显示高剂量TEL雄性幼崽持续活动减少(第15、22、24、26和29天)。TEL处理对被动回避学习没有影响(第18天)。然而,被动回避记忆的72小时和144小时测试(第21天和25天)表明情感行为发生了改变,即高剂量TEL雄性幼崽活动减少,低剂量TEL雌性幼崽活动增加。惊吓反应的数量减少,但幅度未变,这也是TEL暴露的一个作用。因此,产后第5天单次注射TEL产生了可能反映TEL直接药理活性的暂时影响,以及表明行为功能可能发生永久性改变的明显长期影响。

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