Hrushesky W J, Olshefski R, Wood P, Meshnick S, Eaton J W
Lancet. 1985 Mar 9;1(8428):565-7. doi: 10.1016/s0140-6736(85)91218-8.
It was postulated that the therapeutic index of very toxic, oxidative drugs could be improved by concurrent treatment with other agents, such as methylene-blue, which affect the concentration of intracellular reducing agents. In support of this hypothesis, methylene-blue was found to protect mice against the toxic effects of doxorubicin without reducing doxorubicin's antineoplastic activity. Because the clinical usefulness of doxorubicin, the most commonly used and broadly active chemotherapeutic agent, is severely limited by acute and cumulative toxic effects, clinical trials of the effect of methylene-blue on the toxic therapeutic ratio of doxorubicin and other oxidative quinone drugs should be considered.
据推测，通过与其他能影响细胞内还原剂浓度的药物（如亚甲蓝）同时治疗，毒性很强的氧化性药物的治疗指数可能会提高。为支持这一假说，研究发现亚甲蓝可保护小鼠免受阿霉素的毒性作用，同时又不降低阿霉素的抗肿瘤活性。由于阿霉素是最常用且活性广泛的化疗药物，但其临床应用因急性和累积毒性作用而受到严重限制，因此应考虑开展关于亚甲蓝对阿霉素及其他氧化性醌类药物的毒性治疗比影响的临床试验。
