Phlebotomy as a preventive measure for crocidolite-induced mesothelioma in male rats.
Phlebotomy as a preventive measure for crocidolite-induced mesothelioma in male rats.
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DOI：
10.1111/cas.13460
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发表时间：
2018-03
期刊：
影响因子：
5.7
通讯作者：
Toyokuni S
中科院分区：
文献类型：
--
作者：
Ohara Y;Chew SH;Shibata T;Okazaki Y;Yamashita K;Toyokuni S
恶性间皮瘤（MM）是一种罕见但具有重要社会意义的肿瘤，因为它与石棉暴露有关。恶性间皮瘤在早期阶段很难诊断，但在晚期阶段还没有特别有效的治疗方法，因此需要有效的策略来预防已经接触石棉的个体的 MM。我们之前表明，异物反应以及石棉与血红蛋白和组蛋白的亲和力引起的持续氧化损伤是主要发病机制之一。因此，作为预防石棉诱发的多发性骨髓瘤的有效策略，我们使用了铁螯合剂地拉罗司，它可以减少青石棉诱发的大鼠多发性骨髓瘤模型中的上皮-间质转化。然而，这种药物可能会出现不良反应。在这里，我们研究了通过放血去除铁的效果，作为对同一大鼠模型的实际测量。我们总共腹腔注射了 5 毫克青石棉。 6 周龄时，将 Fischer-344 品系和 Brown-Norway 品系的 F1 代杂交大鼠进行实验。从 10 周龄到 60 周龄，我们每周或每两周重复一次 6‐8 mL/kg/次的静脉切开术。观察动物直至 120 周。在雄性大鼠中，放血显着降低了 MM 的重量和核分级，并适度减少了相关的腹水和恶性肉瘤样亚型的比例。每周放血可延长长期生存期。我们的结果表明，适当的放血可能是一种实用的预防措施，可以通过减少接触石棉的个体中的铁来减弱石棉对多发性骨髓瘤的引发和促进能力。
Malignant mesothelioma (MM) is a rare but socially important neoplasm due to its association with asbestos exposure. Malignant mesothelioma is difficult to diagnose at an early stage, yet there are no particularly effective treatments available at the advanced stage, thus necessitating efficient strategies to prevent MM in individuals already exposed to asbestos. We previously showed that persistent oxidative damage caused by foreign body reaction and affinity of asbestos both to hemoglobin and histones is one of the major pathogeneses. Accordingly, as an effective strategy to prevent asbestos‐induced MM, we undertook the use of an iron chelator, deferasirox, which decreased the epithelial–mesenchymal transition in a crocidolite‐induced rat MM model. However, this agent may show adverse effects. Here, we studied the effects of iron removal by phlebotomy as a realistic measure on the same rat model. We injected a total of 5 mg crocidolite i.p. to F1 hybrid rats between the Fischer‐344 and Brown‐Norway strains at the age of 6 weeks. We repeated weekly or biweekly phlebotomy of 6‐8 mL/kg/time from 10 to 60 weeks of age. The animals were observed until 120 weeks. In male rats, phlebotomy significantly decreased the weight and nuclear grade of MM, and modestly reduced the associated ascites and the fraction of more malignant sarcomatoid subtype. Weekly phlebotomy prolonged long‐term survival. Our results indicate that appropriate phlebotomy may be a practical preventive measure to attenuate the initiation and promotion capacity of asbestos towards MM by reducing iron in individuals exposed to asbestos.
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影响因子：
5.6
作者：
Butnor, KJ;Sporn, TA;Roggli, VL
通讯作者：
Roggli, VL
影响因子：
5
作者：
Hu, Qian;Akatsuka, Shinya;Toyokuni, Shinya
通讯作者：
Toyokuni, Shinya
影响因子：
3.8
作者：
BURNS, KF;DELANNOY, CW
通讯作者：
DELANNOY, CW
影响因子：
5.7
作者：
Nagai, Hirotaka;Ishihara, Toshikazu;Toyokuni, Shinya
通讯作者：
Toyokuni, Shinya
影响因子：
4
作者：
Atashi F;Modarressi A;Pepper MS
通讯作者：
Pepper MS