Milaeva E, Petrosyan V, Berberova N, Pimenov Y, Pellerito L
Department of Organic Chemistry, Moscow State Lomonosov University, Lelinsky Gory, Moscow 119899, Russia.
Bioinorg Chem Appl. 2004;2(1-2):69-91. doi: 10.1155/S1565363304000068.
The toxicity mechanisms of mercury and tin organic derivatives are still under debate. Generally the presence of organic moieties in their molecules makes these compounds lipophilic and membrane active species. The recent results suggest that Hg and Sn compounds deplete HS-groups in proteins, glutathione and glutathione-dependent enzymatic systems; this process also results in the production of reactive oxygen species (ROS), the enhancement of membrane lipids peroxidation and damage of the antioxidative defence system. The goal of this review is to present recent results in the studies oriented towards the role of organomercury and organotin compounds in the xenobiotic-mediated enhancement of radical production and hence in the promotion of cell damage as a result of enhanced lipids peroxidation. Moreover the conception of the carbon to metal bond cleavage that leads to the generation of reactive organic radicals is discussed as one of the mechanisms of mercury and tin organic derivatives toxicity. The possible use of natural and synthetic antioxidants as detoxification agents is described. The data collected recently and presented here are fundamentally important to recognizing the difference between the role of metal center and of organic fragments in the biochemical behavior of organomercury and organotin compounds in their interaction with primary biological targets when entering a living organism.
汞和锡的有机衍生物的毒性机制仍在争论中。一般来说,它们分子中有机部分的存在使这些化合物具有亲脂性且成为膜活性物质。最近的研究结果表明,汞和锡化合物会消耗蛋白质、谷胱甘肽及谷胱甘肽依赖性酶系统中的巯基;这一过程还会导致活性氧(ROS)的产生、膜脂过氧化的增强以及抗氧化防御系统的损伤。本综述的目的是展示近期研究结果,这些研究旨在探讨有机汞和有机锡化合物在异生物质介导的自由基产生增强中所起的作用,以及由此因脂质过氧化增强而促进细胞损伤的作用。此外,还讨论了导致活性有机自由基产生的碳 - 金属键断裂概念,将其作为汞和锡有机衍生物毒性的一种机制。还描述了天然和合成抗氧化剂作为解毒剂的可能用途。最近收集并在此呈现的数据对于认识金属中心和有机片段在有机汞和有机锡化合物进入活生物体后与主要生物靶点相互作用时的生化行为中所起作用的差异至关重要。