THE CATECHOLIC METAL SEQUESTERING AGENT 1,2-DIHYDROXYBENZENE-3,5-DISULFONATE CONFERS PROTECTION AGAINST OXIDATIVE CELL-DAMAGE
THE CATECHOLIC METAL SEQUESTERING AGENT 1,2-DIHYDROXYBENZENE-3,5-DISULFONATE CONFERS PROTECTION AGAINST OXIDATIVE CELL-DAMAGE
复制标题
DOI：
10.1016/0003-9861(92)90142-j
复制
发表时间：
1992-04-01
影响因子：
3.9
通讯作者：
RUSSO, A
中科院分区：
文献类型：
--
作者：
KRISHNA, CM;LIEBMANN, JE;RUSSO, A
摘要Tiron（1，2-二羟基苯-3，5-二磺酸盐）是一种无毒的金属螯合剂，可用于缓解动物急性金属超负荷。它也被氧化为EPR可检测的半醌自由基的各种生物相关的氧化剂，如。OH、OH、烷基和烷氧基。由于Tiron与潜在的有毒细胞内物种反应，也是一种金属螯合剂，我们评估了其在V79细胞中的保护作用，受到各种类型的氧化损伤，并试图区分保护由于直接解毒的细胞内自由基的氧化还原活性的过渡金属螯合。克隆形成实验表明，Tiron通过使O fx 98 -3 2和H2 O2诱导的细胞毒性发生突变，从而保护中国仓鼠V79细胞免受O fx 98 -2 2和H2 O2诱导的细胞毒性。在将Tiron与V79细胞一起孵育并在暴露于HX XO或H2 O2之前冲洗的实验中，观察到细胞保护作用，表明其保护细胞免受细胞内氧化损伤。另一方面，Tiron不能保护V79细胞免受电离辐射在有氧条件下引起的损伤，这主要是由H. OH和水合电子以不依赖于金属的方式。我们还证明，在体外研究中，Tiron保护超螺旋DNA从金属介导的超氧化物依赖性链断裂。我们的结论是，Tiron是一种潜在的有用的保护剂对氧化应激的致死作用，并建议它提供保护螯合氧化还原活性的过渡金属离子，在早期的报告中，这种化合物在细胞系统中受到氧化损伤的保护已被解释为由于自由基清除单独。
Abstract Tiron (1, 2-dihydroxybenzene-3, 5-disulfonate), a non-toxic chelator of a variety of metals, is used to alleviate acute metal overload in animals. It is also oxidized to the EPR-detectable semiquinone radical by various biologically relevant oxidants, such as. OH, O fx98-1 2 alkyl, and alkoxyl radicals. Since Tiron reacts with potentially toxic intracellular species and is also a metal chelator, we evaluated its protective effects in V79 cells subjected to various types of oxidative damage and attempted to distinguish the protection due to direct detoxification of intracellular radicals from that resulting from chelation of redox-active transition metals. We found that Tiron protects Chinese hamster V79 cells against both O fx98-2 2-induced (and H 2 O 2 via dismutation of O fx98-3 2 and H 2 O 2-induced cytotoxicity as measured by clonogenic assays. In experiments where Tiron was incubated with V79 cells and rinsed prior to exposure to HX XO or H 2 O 2, cytoprotection was observed, indicating that it protects against intracellular oxidative damage. On the other hand, Tiron did not protect V79 cells against the damage caused by ionizing radiation under aerobic conditions, which is predominantly mediated by H.,. OH, and hydrated electrons in a metal-independent fashion. We demonstrate also that in in vitro studies, Tiron protects supercoiled DNA from metal-mediated superoxide-dependent strand breaks. We conclude that Tiron is a potentially useful protecting agent against the lethal effects of oxidative stress and suggest that it offers protection by chelating redox-active transition metal ions, in contrast to earlier reports where the protection by this compound in cellular systems subjected to oxidative damage has been interpreted as due to radical scavenging alone.