Role of iron in asbestos-body-induced oxidant radical generation
Role of iron in asbestos-body-induced oxidant radical generation
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DOI：
10.1080/009841099157241
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发表时间：
1999-11-12
期刊：
影响因子：
--
通讯作者：
Bo, P
中科院分区：
文献类型：
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作者：
Governa, M;Amati, M;Bo, P
从人肺组织中收集石棉体（AB），并从未涂覆的石棉纤维中分离。将含有1000 AB的样品加入反应溶液中，以研究AB在抗坏血酸盐和过氧化氢存在下氧化脱氧-D-核糖并产生活性氧物质（ROS）的能力，如通过硫代巴比妥酸（TBA）反应产物的形成所确定的。测试了三种类型的石棉纤维进行比较，因为已知它们能够产生ROS。用1000 AB测得的吸光度值明显高于用1000三种石棉纤维测得的值。由于在我们的反应体系中，过渡金属的唯一来源是富铁AB，数据表明来自AB的铁蛋白涂层的铁参与氧化剂的产生。此外，铁AB增强TEA反应产物的形成，而螯合铁与去铁胺减少了这一反应。羟自由基清除剂1，3-二甲基-2-硫脲（DMTU）和甘露醇（MN）也有效地阻断TEA反应性产物的产生。数据表明铁在AB诱导的氧化损伤中的重要性。随着向AB中加入多形核白细胞（PMN），在反应溶液中孵育得到非常高量的TEA反应产物，但使用不含抗坏血酸的反应溶液，产生非常低量的TBA反应产物。在后一种情况下，细胞膜的超氧化物可能减少并除去AB-包被铁蛋白中的铁，但不如抗坏血酸有效。此外，在Fe 2+的可能的再氧化之后，Fe 3+可以被乳铁蛋白配位。由于还原剂的这种可用性在生命系统中从未接近，AB涂层中的铁不太可能在体内充当芬顿型反应的催化剂。
Asbestos bodies (AB) were harvested from human lung tissue digests and isolated from uncoated asbestos fibers. Samples containing 1000 AB were added to a reactive solution to investigate the ability of AB to oxidize deoxy-D-ribose and generate reactive oxygen species (ROS) in the presence of ascorbate and hydrogen peroxide as determined by formation of thiobarbituric acid (TBA)-reactive products. Three types of asbestos fibers were tested for comparison, since they are known to be able to produce ROS. The absorbance values measured with 1000 AB were significantly higher than those observed with 1000 fibers of the three types of asbestos. Since in our reaction system the only source of transition metals was the iron-rich AB, data suggest iron derived from the ferritin coating of AB was involved in oxidant generation. Addition of iron to AB enhanced TEA-reactive product formation, while chelation of Fe with deferoxamine reduced this reaction. Hydroxyl radical scavengers 1,3-dimethyl-2-thourea (DMTU) and mannitol (MN) also effectively blocked TEA-reactive product generation. Data indicate the importance of Fe in AB-induced oxidant damage. With the addition of polymorphonuclear leukocytes (PMN) to AB, incubation in the reactive solution gave very high amounts of TEA-reactive products, but using a reactive solution devoid of ascorbate, very low amounts of TBA-reactive products were generated. in the latter condition, the superoxide of cell membranes probably reduced and removed iron from AB-coating ferritin, but less effectively than ascorbate. Further after the possible reoxidation of Fe2+, Fe3+ could be coordinated by lactoferrin. Since such availability of reductant is never approached in living systems, the iron in the AB coating is unlikely to function as a catalyst of Fenton-type reactions in vivo.