6-gingerol ameliorated doxorubicin-induced cardiotoxicity: role of nuclear factor kappa B and protein glycation
6-gingerol ameliorated doxorubicin-induced cardiotoxicity: role of nuclear factor kappa B and protein glycation
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DOI：
10.1007/s00280-012-1975-y
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发表时间：
2012-12-01
影响因子：
3
通讯作者：
Schaalan, Mona F.
中科院分区：
文献类型：
--
作者：
El-Bakly, Wesam M.;Louka, Manal L.;Schaalan, Mona F.
目的阿霉素是一种应用广泛的抗肿瘤药物。心脏毒性被认为是其临床应用的主要限制因素。本研究旨在探讨6-姜辣素在减轻阿霉素所致心肌损伤中可能的抗氧化和抗细胞凋亡作用。方法雄性大鼠给予阿霉素(18 mg/kg，分成6个等量剂量，连续2周)和/或口服6-姜辣素(10 mg/kg，从实验前5天开始至实验结束)。结果6-姜辣素可明显改善阿霉素所致的心肌酶活性升高。阿霉素对氧化应激的刺激表现为血清晚期糖基化终产物的可溶性受体显着降低，从而使血清晚期糖基化终产物的可用性不受影响。此外，阿霉素还激活了核因子-kappaB，其免疫组织化学染色在细胞核中的表达增加。此外，阿霉素所致的心脏毒性还伴随着心脏caspase-3的升高。值得注意的是，6-姜辣素可显著改善SRAGE、核因子-kappaB和心脏caspase-3的变化。心肌酶与核因子-kappaB、半胱氨酸天冬氨酸氨基转移酶-3呈显著正相关，与血清sRAGE呈显著负相关，提示其在阿霉素心脏损伤中的作用。结论6-姜酚是一种已知的具有抗癌活性的生姜单体化合物，对阿霉素引起的心脏毒性具有良好的保护作用。本研究提出了6-姜辣素的一种新的心脏保护机制，其机制可能与其抗氧化作用、调节核因子-kappaB及细胞凋亡有关。
Purpose Doxorubicin is a widely used antitumour drug. Cardiotoxicity is considered a major limitation for its clinical use. The present study was designed to assess the possible antioxidant and antiapoptotic effects of 6-gingerol in attenuating doxorubicin-induced cardiac damage.Methods Male albino rats were treated with either intraperitoneal doxorubicin (18 mg/kg divided into six equal doses for 2 weeks) and/or oral 6-gingerol (10 mg/kg starting 5 days before and continued till the end of the experiment).Results 6-gingerol significantly ameliorated the doxorubicin-induced elevation in the cardiac enzymes. The stimulation of oxidative stress by doxorubicin was evidenced by the significant decrease in the serum soluble receptor for advanced glycation endproduct allowing unopposed serum advanced glycation endproduct availability. Moreover, doxorubicin activated nuclear factor kappa B (NF-kappa B) which was indicated by an increase in its immunohistochemical staining in the nucleus. In addition, doxorubicin-induced cardiotoxicity was accompanied by elevation of cardiac caspase-3. Notably, pretreatment with 6-gingerol significantly ameliorated the changes in sRAGE, NF-kappa B and cardiac caspase-3. Cardiac enzymes showed significant positive correlation with NF-kappa B and caspase-3 but negative with serum sRAGE, suggesting their role in doxorubicin-induced cardiac injury. These findings were confirmed by cardiac tissue histopathology.Conclusions 6-gingerol, a known single compound from ginger with anticancer activity, was shown to have a promising role in cardioprotection against doxorubicin-induced cardiotoxicity. This study suggested a novel mechanism for 6-gingerol cardioprotection, which might be mediated through its antioxidative effect and modulation of NF-kappa B as well as apoptosis.