Institute of Molecular Toxicology and Pharmacology, Helmholtz Center Munich, German Research Center for Environmental Health, D-85764 Neuherberg, Germany.
CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal.
Int J Mol Sci. 2024 Jul 18;25(14):7880. doi: 10.3390/ijms25147880.
Essential transition metals have key roles in oxygen transport, neurotransmitter synthesis, nucleic acid repair, cellular structure maintenance and stability, oxidative phosphorylation, and metabolism. The balance between metal deficiency and excess is typically ensured by several extracellular and intracellular mechanisms involved in uptake, distribution, and excretion. However, provoked by either intrinsic or extrinsic factors, excess iron, zinc, copper, or manganese can lead to cellular damage upon chronic or acute exposure, frequently attributed to oxidative stress. Intracellularly, mitochondria are the organelles that require the tightest control concerning reactive oxygen species production, which inevitably leaves them to be one of the most vulnerable targets of metal toxicity. Current therapies to counteract metal overload are focused on chelators, which often cause secondary effects decreasing patients' quality of life. New therapeutic options based on synthetic or natural antioxidants have proven positive effects against metal intoxication. In this review, we briefly address the cellular metabolism of transition metals, consequences of their overload, and current therapies, followed by their potential role in inducing oxidative stress and remedies thereof.
必需的过渡金属在氧气运输、神经递质合成、核酸修复、细胞结构维持和稳定、氧化磷酸化和代谢中发挥关键作用。金属缺乏和过量之间的平衡通常由涉及摄取、分布和排泄的几种细胞外和细胞内机制来保证。然而，无论是内在的还是外在的因素引起的，过量的铁、锌、铜或锰在慢性或急性暴露下会导致细胞损伤，这通常归因于氧化应激。在细胞内，线粒体是对活性氧产生要求最严格的细胞器，这不可避免地使它们成为金属毒性最脆弱的目标之一。目前对抗金属过载的治疗方法集中在螯合剂上，而这些螯合剂往往会引起降低患者生活质量的副作用。基于合成或天然抗氧化剂的新治疗选择已被证明对金属中毒有积极影响。在这篇综述中，我们简要讨论了过渡金属的细胞代谢、它们过载的后果以及当前的治疗方法，接着讨论了它们在诱导氧化应激及其补救措施中的潜在作用。
