Cobalt-mediated oxidative DNA damage and its prevention by polyphenol antioxidants
Cobalt-mediated oxidative DNA damage and its prevention by polyphenol antioxidants
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DOI：
10.1016/j.jinorgbio.2022.112024
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发表时间：
2022-10-19
影响因子：
3.9
通讯作者：
Brumaghim，Julia L.
中科院分区：
文献类型：
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作者：
Angele-Martinez，Carlos;Murray，Joseph;Brumaghim，Julia L.
虽然钴是必需的营养素，但由于它能够产生活性氧 (ROS) 并损伤 DNA，因此具有毒性。通常将 Co2+ 产生的 ROS 与 Fe2+ 或 Cu+ 产生的 ROS 进行比较，忽略这些金属离子之间的还原电位差异。在质粒 DNA 损伤研究中，Co2+/H2O2 处理（分别高达 50 μM 和 400 μM）最多观察到 15% DNA 损伤，显着低于 Fe2+/H2O2 或 Cu+/H2O2 处理观察到的 90% 损伤。然而，当抗坏血酸添加到 Co2+/H2O2 系统中时，协同效应会导致 90% 的 DNA 损伤。多酚抗氧化剂可以预防 Fe2+/H2O2 造成的 DNA 损伤，但多酚既可以预防又促进 Cu+/H2O2 造成的 DNA 损伤。在测试钴介导的 DNA 损伤影响时，十种多酚中的八种（表儿茶素没食子酸酯、表没食子儿茶素没食子酸酯、没食子酸丙酯、没食子酸、3,4,5-三羟基苯甲酸甲酯、4,5-二羟基苯甲酸甲酯、原儿茶酸和表儿茶素）可以预防钴介导的 DNA 损伤 IC50 值为 1.3 至 27 μM，两种（表没食子儿茶素和香草酸）几乎不会防止 DNA 损伤。 EPR 研究表明，在 H2O2 和抗坏血酸存在的情况下，钴介导形成•OH、O2•ˉ 和•OOH，但不会形成1O2。表没食子儿茶素没食子酸酯和 4,5-二羟基苯甲酸甲酯可显着减少 Co2+/H2O2/抗坏血酸产生的 ROS，这与它们预防钴介导的 DNA 损伤的作用一致。因此，虽然钴、铁和铜都是阻滞金属离子，但钴ROS的产生及其预防与铁和铜显着不同。
Although cobalt is a required nutrient, it is toxic due to its ability to generate reactive oxygen species (ROS) and damage DNA. ROS generation by Co2+often has been compared to that of Fe2+or Cu+, disregarding the reduction potential differences among these metal ions. In plasmid DNA damage studies, a maximum of 15% DNA damage is observed with Co2+/H2O2treatment (up to 50 μM and 400 μM, respectively) significantly lower than the 90% damage observed for Fe2+/H2O2or Cu+/H2O2treatment. However, when ascorbate is added to the Co2+/H2O2system, a synergistic effect results in 90% DNA damage. DNA damage by Fe2+/H2O2can be prevented by polyphenol antioxidants, but polyphenols both prevent and promote DNA damage by Cu+/H2O2. When tested for cobalt-mediated DNA damage affects, eight of ten polyphenols (epicatechin gallate, epigallocatechin gallate, propyl gallate, gallic acid, methyl-3,4,5-trihydroxybenzoate, methyl-4,5-dihydroxybenzoate, protocatechuic acid, and epicatechin) prevent cobalt-mediated DNA damage with IC50values of 1.3 to 27 μM and two (epigallocatechin and vanillic acid) prevent little to no DNA damage. EPR studies demonstrate cobalt-mediated formation of•OH, O2•ˉ, and•OOH, but not1O2in the presence of H2O2and ascorbate. Epigallocatechin gallate and methyl-4,5-dihydroxybenzoate significantly reduce ROS generated by Co2+/H2O2/ascorbate, consistent with their prevention of cobalt-mediated DNA damage. Thus, while cobalt, iron, and copper are alld-block metal ions, cobalt ROS generation and its prevention is significantly different from that of iron and copper.