The changing view of acrylamide neurotoxicity
The changing view of acrylamide neurotoxicity
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DOI：
10.1016/j.neuro.2004.01.004
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发表时间：
2004-06-01
期刊：
影响因子：
3.4
通讯作者：
LoPachin, RM
中科院分区：
文献类型：
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作者：
LoPachin, RM
丙烯酰胺（ACR）是一种水溶性乙烯基单体，具有多种化学和工业应用：例如，废水管理，矿石处理。此外，ACR广泛用于分子实验室的凝胶层析，也存在于某些在高温下制备的食品中。对啮齿动物和其他实验动物的广泛研究提供了证据，表明接触单体ACR会导致神经系统和生殖系统的细胞损伤，并在某些激素反应性组织中产生肿瘤。尽管人类流行病学研究表明，在职业暴露人群中，神经毒性发生率显著升高，但迄今为止，此类研究尚未显示癌症风险相应增加。自2002年4月瑞典一个研究小组宣布这一消息以来[J]。Ag)。食品化学，50(2002)4998]关于马铃薯和谷类食品中ACR的存在，人们对这种化学物质的毒性作用重新产生了兴趣。因此，在这篇综述中，我们考虑ACR的不同毒性作用。ACR的神经毒性作用将成为焦点，因为神经毒性是人类和实验动物暴露的结果，而且这一调查领域在过去30年中受到了相当大的关注。正如我们将要讨论的，现在越来越多的证据表明，神经末梢是ACR作用的主要部位，抑制相应的膜融合过程会损害神经递质释放并促进最终的变性。ACR的亲电性质表明，这种神经毒物在某些关键参与膜融合的蛋白质上加合亲核巯基。巯基的内合也可能与ACR的生殖和致癌作用有关。本综述的最终目标是确定阻碍对ACR病理生理过程全面理解的数据差距。(C) 2004爱思唯尔公司版权所有。
Acrylamide (ACR) is a water-soluble, vinyl monomer that has multiple chemical and industrial applications: e.g., waste water management, ore processing. In addition, ACR is used extensively in molecular laboratories for gel chromatography and is present in certain foods that have been prepared at very high temperatures. Extensive studies in rodents and other laboratory animals have provided evidence that exposure to monomeric ACR causes cellular damage in both the nervous and reproductive systems, and produces tumors in certain hormonally responsive tissues. Whereas human epidemiological studies have demonstrated a significantly elevated incidence of neurotoxicity in occupationally exposed populations, such research has not, to date, revealed a corresponding increase in cancer risk. Since the announcement by a Swedish research group in April 2002 [J. Ag. Food Chem. 50 (2002) 4998] regarding the presence of ACR in potato and grain-basedfoods, there has been a renewed interest in the toxic actions of this chemical. Therefore, in this review, we consider the different toxic effects of ACR. The neurotoxic actions of ACR will be the focal point since neurotoxicity is a consequence of both human and laboratory animal exposure and since this area of investigation has received considerable attention over the past 30 years. As will be discussed, a growing body of evidence now indicates that the nerve terminal is a primary site of ACR action and that inhibition of corresponding membrane-fusion processes impairs neurotransmitter release and promotes eventual degeneration. The electrophilic nature of ACR suggests that this neurotoxicant adducts nucleophilic sulfhydryl groups on certain proteins that are critically involved in membrane fusion. Adduction of thiol groups also might be common to the reproductive and carcinogenic effects of ACR. A final goal of this review is to identify data gaps that retard a comprehensive understanding of ACR pathophysiological processes. (C) 2004 Elsevier Inc. All rights reserved.