Protective effect of ocotillol against doxorubicin-induced acute and chronic cardiac injury
Protective effect of ocotillol against doxorubicin-induced acute and chronic cardiac injury
复制标题
奥克替洛对阿霉素所致急慢性心脏损伤的保护作用
DOI：
10.3892/mmr.2013.1791
复制
发表时间：
2014-01-01
影响因子：
3.4
通讯作者：
Fu, Fenghua
中科院分区：
文献类型：
--
作者：
Fu, Xiaoya;Kong, Liang;Fu, Fenghua
阿霉素（Dox）具有显著的抗癌活性。然而，它受到其相关剂量依赖性心脏毒性的严重限制，可以通过与无毒增敏剂结合减少累积剂量来减弱这种毒性。我们以前报道过，奥科替洛尔能够增强阿霉素的抗肿瘤活性，然而，奥科替洛尔对其心脏毒性的影响尚不清楚。在本研究中，研究了奥科替洛尔对Dox毒性的影响，特别是其在心脏毒性中的作用。在急性损伤模型中，预先给予奥可洛尔可延长存活时间。在慢性动物模型中，预先给药奥可洛尔可降低升高的血浆肌酸激酶（CK）和CK-MB水平，并减轻所发生的病理变化。奥可替洛尔预处理可改善心脏组织中谷胱甘肽水平的下降，并减少累积的丙二醛。此外，奥可替洛预处理恢复了降低的白色血细胞计数。结果表明，Dox与Ocotillol的联合治疗可以有效地减轻其相关的毒性损伤，特别是心脏毒性。因此，与奥可替洛尔的Dox的共同施用可能是一种潜在的治疗策略。
Doxorubicin (Dox) has been clinically observed to exert marked anticancer activity. However, it is severely restricted by its associated dose-dependent cardiotoxicity, which may be attenuated by decreasing the cumulative dosage via combining with a non-toxic sensitizer'. We previously reported that ocotillol is capable of enhancing the antitumor activity of Dox; however, the effects of ocotillol on its cardiotoxicity remain unclear. In the current study, the effects of ocotillol on the toxicity of Dox were investigated, particularly its role in cardiotoxicity. In the acute injury model, pre-administration of ocotillol prolonged the survival time. In the chronic animal model, pre-administration of ocotillol decreased the elevated levels of plasma creatine kinase (CK) and CK-MB, as well as attenuated the pathological changes that occurred. Pre-treatment with ocotillol ameliorated the decreased glutathione level and reduced the cumulated malondialdehyde in the heart tissue. In addition, pre-treatment with ocotillol restored the lowered white blood cell count. The results indicate that Dox co-treatment with ocotillol may effectively alleviate its associated toxic injury, particularly cardiotoxicity. Thus, co-administration of Dox with ocotillol may be a potential therapeutic strategy.