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[环境化学物质诱导的神经毒性效应的生物标志物]

[Biomarkers of neurotoxic effects induced by environmental chemicals].

作者信息

Indulski J A, Lutz W

机构信息

Instytutu Medycyny Pracy, Lodzi.

出版信息

Med Pr. 1996;47(4):383-91.

PMID:8847985
Abstract

Biological monitoring of neurotoxic effects induced by environmental chemicals covers a very broad spectrum of measurements beginning with molecular, subcellular and cellular changes through neurophysiological and neurobehavioral ones. For many years epidemiological studies had employed almost entirely neurophysiological and neurobehavioural ones. For many years epidemiological studies had employed almost entirely neurophysiological and neurobehavioural tests in the assessment of the magnitude and effects of exposure to neurotoxins. Only in the recent past, due to paramount advances in experimental biochemical toxicology, the application of biochemical tests-biomarkers of exposure, health effects and susceptibility-in neuroepidemiological studies became realistic. That was also associated with the detection of molecular targets for neurotoxins and the explanation of mechanisms of their effect. Exposure biomarkers define an absorbed dose and provide a quantitative measurement of adducts produced by neurotoxin (or its metabolite) or products of interaction with endogenic substances, for example, with DNA or enzymatic proteins. Biomarkers of health effects provide information on changes in the nervous system which occurred in its different sections: organic, tissular, cellular, subcellular and molecular, due to exposure to neurotoxic agents. Biomarkers of susceptibility inform that in a given person or population adverse health effects may be expected in the nervous system in the case of lower or higher exposure to a neurotoxic agent. They may prove useful in assessing the probability of progress in the disease of the nervous system due to exposure to environmental neurotoxins. They are measurable indicators of the nervous system biological factors which occur prior to exposure and are genetically determined or acquired. The latter may result from past diseases of the nervous system or earlier exposure to neurotoxic agents. The fact that the targeted cell-the nervous tissue-cannot be explored directly is one of the most important obstacles which still hinders the monitoring of neurotoxic effects by means of biochemical tests. On account of this limitation, in order to identify and characterise neurotoxic features, it is necessary to use those biochemical parameters which exist in easily accessible peripheral tissues, and which correspond with the parameters of the nervous tissue. It has thus far been found that biochemical markers present in the morphotic elements of peripheral blood (plates, leucocytes, erythrocytes) can be used as measurable, substitutive indicators of damages, dysfunctions and interactions in the nervous system caused by environmental neurotoxins.

摘要

环境化学物质所致神经毒性效应的生物监测涵盖了非常广泛的测量范围,从分子、亚细胞和细胞变化,到神经生理和神经行为变化。多年来,流行病学研究几乎完全采用神经生理和神经行为测量方法。多年来,流行病学研究在评估神经毒素暴露的程度和影响时,几乎完全采用神经生理和神经行为测试。只是在最近,由于实验生化毒理学取得了重大进展,生化测试(暴露、健康效应和易感性的生物标志物)在神经流行病学研究中的应用才变得切实可行。这也与神经毒素分子靶点的发现及其作用机制的解释有关。暴露生物标志物可确定吸收剂量,并对神经毒素(或其代谢物)产生的加合物或与内源性物质(如DNA或酶蛋白)相互作用的产物进行定量测量。健康效应生物标志物可提供因接触神经毒性物质而在神经系统不同部位(器官、组织、细胞、亚细胞和分子水平)发生变化的信息。易感性生物标志物表明,在特定个体或人群中,较低或较高水平接触神经毒性物质时,神经系统可能会出现不良健康效应。它们可能有助于评估因接触环境神经毒素而导致神经系统疾病进展的可能性。它们是神经系统生物因素的可测量指标,这些因素在接触之前就已存在,由遗传决定或后天获得。后者可能源于过去的神经系统疾病或早期接触神经毒性物质。无法直接检测目标细胞——神经组织——这一事实,是目前仍然阻碍通过生化测试监测神经毒性效应的最重要障碍之一。由于这一限制,为了识别和表征神经毒性特征,有必要使用那些存在于易于获取的外周组织中、且与神经组织参数相对应的生化参数。迄今为止已经发现,外周血形态成分(血小板、白细胞、红细胞)中存在的生化标志物,可用作环境神经毒素所致神经系统损伤、功能障碍和相互作用的可测量替代指标。

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