摘要
背景:必需金属离子在人体新陈代谢中发挥着特殊而基本的作用。它们的体内平衡经过精细调整,任何浓度不足或过量的失衡都可能导致正常生物功能的逐渐降低和失效,导致严重的生理和临床后果,最终可能导致死亡。相反,非必需金属不是生命所必需的,接触后只会产生有害影响。环境中大量的此类化学品来自自然和人为来源,而后者主要是由于人类活动造成的。有毒金属的扩散会污染水、空气、土壤和食物,引起一系列慢性和急性综合征。 目的:这篇综述讨论了非必需金属的毒性,考虑到它们独特的化学特性,如不同的形式、软硬特性、氧化态、结合能力和溶解度,这些特性会影响它们在生物系统中的形态,随后,主要细胞靶点。特别关注选定的有毒金属、主要非必需金属或与毒性相关的半金属,例如汞、铅、镉、铬、镍和砷。此外,我们还提供了基于螯合疗法的金属中毒可能的治疗/干预适应症。 结论:有毒金属离子可以通过多种方式发挥其特有的有害作用。它们根据重要的生物分子的化学物理特性(主要是 HSAB 特性)与重要的生物分子强烈协调,或者从蛋白质、酶或硬结构(如骨骼或牙齿)中的天然位置替换必需的金属离子。具有氧化还原特性的金属可能是活性氧的关键诱导剂,导致氧化应激和细胞损伤。治疗性解毒,通过特定螯合剂络合有毒金属离子,似乎是一种有效的临床策略,主要用于金属中毒的急性病例。
关键词: 金属形态,金属毒性,螯合疗法,有毒金属,金属中毒,氧化态。
Current Medicinal Chemistry
Title:Metal Toxicity and Speciation: A Review
Volume: 28 Issue: 35
关键词: 金属形态,金属毒性,螯合疗法,有毒金属,金属中毒,氧化态。
摘要:
Background: Essential metal ions play a specific and fundamental role in human metabolism. Their homeostasis is finely tuned, and any concentration imbalance in the form of deficiency or excess could lead to a progressive reduction and failure of normal biological function, to severe physiological and clinical outcomes, may eventually causing death. Conversely, non-essential metals are not necessary for life, and only noxious effects could arise after their exposure. Large environmental amounts of such chemicals come from both natural and anthropogenic sources, with the latter being predominant because of human activities. The dissipation of toxic metals contaminates water, air, soil, and food, causing a series of chronic and acute syndromes.
Objective: This review discusses the toxicity of non-essential metals considering their peculiar chemical characteristics, such as different forms, hard-soft character, oxidation states, binding capabilities, and solubility, which can influence their speciation in biological systems, and subsequently, the main cellular targets. Particular focus is given to selected toxic metals, major non-essential metals, or semimetals related to toxicity, such as mercury, lead, cadmium, chromium, nickel, and arsenic. In addition, we provide indications on the possible treatments/interventions for metal poisoning based on chelation therapy.
Conclusion: Toxic metal ions can exert their peculiar harmful effects in several ways. They strongly coordinate with important biological molecules on the basis of their chemical- physical characteristics (mainly HSAB properties) or replace essential metal ions from their natural locations in proteins, enzymes, or hard structures, such as bones or teeth. Metals with redox properties could be key inducers of reactive oxygen species, leading to oxidative stress and cellular damage. Therapeutic detoxification, through complexation of toxic metal ions by specific chelating agents, appears an efficacious clinical strategy, mainly in acute cases of metal intoxication.
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Cite this article as:
Metal Toxicity and Speciation: A Review, Current Medicinal Chemistry 2021; 28 (35) . https://dx.doi.org/10.2174/0929867328666210324161205
DOI https://dx.doi.org/10.2174/0929867328666210324161205 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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