Department of Chemistry and Pharmacy, University of Sassari, Sassari, Italy.
Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy.
Curr Med Chem. 2021;28(35):7190-7208. doi: 10.2174/0929867328666210324161205.
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.
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.
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.
必需金属离子在人类代谢中发挥着特定且基础的作用。它们的体内平衡被精细地调节,任何形式的缺乏或过量的浓度失衡都可能导致正常生物功能的逐渐减少和衰竭,产生严重的生理和临床后果,最终可能导致死亡。相反,非必需金属对于生命并非必需,只有在暴露后才会产生有害影响。大量的此类化学物质来自于自然和人为来源,后者由于人类活动而占主导地位。有毒金属的扩散污染了水、空气、土壤和食物,导致一系列慢性和急性综合征。
本综述讨论了非必需金属的毒性,考虑到它们特殊的化学特性,如不同的形式、软硬特性、氧化态、配位能力和溶解度,这些特性可以影响它们在生物系统中的形态,进而影响主要的细胞靶标。特别关注一些具有毒性的选定的有毒金属、主要的非必需金属或类金属,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/干预措施的相关信息。
有毒金属离子可以通过多种方式发挥其特殊的有害作用。它们基于其物理化学特性(主要是 HSAB 特性)与重要的生物分子强烈配位,或者从蛋白质、酶或硬组织(如骨骼或牙齿)中它们的天然位置取代必需金属离子。具有氧化还原性质的金属可能是活性氧物质的关键诱导剂,导致氧化应激和细胞损伤。通过特定的螯合剂与有毒金属离子络合进行治疗性解毒,是一种有效的临床策略,主要适用于急性金属中毒病例。