Repeated Exposures to Subthreshold Doses of Chlorpyrifos in Rats: Hippocampal Damage, Impaired Axonal Transport, and Deficits in Spatial Learning
Repeated Exposures to Subthreshold Doses of Chlorpyrifos in Rats: Hippocampal Damage, Impaired Axonal Transport, and Deficits in Spatial Learning
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大鼠反复暴露于阈下剂量的毒死蜱：海马损伤、轴突运输受损和空间学习缺陷
DOI：
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发表时间：
2003
影响因子：
3.5
通讯作者：
M. Prendergast
中科院分区：
文献类型：
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作者：
Alvin V. Terry;J. Stone;J. J. Buccafusco;D. W. Sickles;Ajay Sood;M. Prendergast
有机磷(OP)化合物在使用后多年仍可在环境中检测到，并对许多人群造成危害。尽管许多OP化合物的剧毒剂量的影响已被很好地描述，但对反复低水平暴露的了解要少得多。这些研究的目的是进一步评估广泛使用的OP杀虫剂毒死蜱(CPF)对大鼠的潜在毒理学效应。在一定的亚阈值剂量范围内(即急性毒性)，CPF可减少饲养和嗅探活动，并减少重复暴露14天的体重增加幅度。暴露于CPF(18.0 mg/kg和25.0 mg/kg)14天后，在最后一次注射后24小时开始测试时，空间学习任务中的成绩受到损害，但在14天清洗后不受影响。然而，25.0 mg/kg的CPF对快速顺行和逆行轴突运输均有抑制作用，持续时间长达20天。使用海马区培养的研究表明，连续8天暴露于母体化合物CPF(≥100μM)会导致细胞毒性和死亡。此外，每周给药5天，连续给药38天，剂量为2.5 mg/kg的CPF对体重增加或记忆能力没有影响，在测试的后几天会损害前肢的握力。总而言之，这些结果表明，重复暴露于阈值以下剂量的CPF可能会导致生长迟缓、行为异常和肌肉无力。其中一些症状可能归因于OP对轴突运输的影响。
Organophosphorus (OP) compounds are detectable in the environment for years after use and endanger many populations. Although the effects of acutely toxic doses of many OP compounds are well described, much less is known about repeated low-level exposures. The purpose of these studies was to further evaluate potential toxicological effects of the extensively used OP pesticide chlorpyrifos (CPF) in rats. CPF, across a range of subthreshold doses (i.e., for acute toxicity), reduced rearing and sniffing activity and the magnitude of weight gain over 14 days of repeated exposure. Performance in a spatial learning task was impaired after 14 days of exposure to CPF (18.0 and 25.0 mg/kg) when testing was initiated 24 h after the last injection but not after a 14-day washout. However, inhibition of both fast anterograde and retrograde axonal transport was observed for up to 20 days after exposure to 25.0 mg/kg CPF. Studies using hippocampal cultures indicated that 8 days of continuous exposure to the parent compound, CPF (≥100 μM), resulted in cell toxicity and death. Furthermore, a dose (2.5 mg/kg) of CPF that had no effects on weight gain or memory performance when administered 5 days per week over 38 days impaired forelimb grip strength in the later days of testing. Collectively, these results indicate that repeated exposures to subthreshold doses of CPF may lead to growth retardation, behavioral abnormalities, and muscle weakness. Some of these symptoms may be attributed to effects of the OP on axonal transport.