Department of Pharmacology and Therapeutics, Faculty of Medicine, Ain Shams University, Abbasia, Cairo, Egypt.
Cancer Chemother Pharmacol. 2012 Dec;70(6):833-41. doi: 10.1007/s00280-012-1975-y. Epub 2012 Sep 27.
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.
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).
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-κB) 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-κB and cardiac caspase-3. Cardiac enzymes showed significant positive correlation with NF-κB and caspase-3 but negative with serum sRAGE, suggesting their role in doxorubicin-induced cardiac injury. These findings were confirmed by cardiac tissue histopathology.
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-κB as well as apoptosis.
多柔比星是一种广泛应用的抗肿瘤药物。其临床应用的主要限制因素是心脏毒性。本研究旨在评估 6-姜酚减轻多柔比星诱导的心脏损伤的可能抗氧化和抗凋亡作用。
雄性白化大鼠分别用腹腔内多柔比星（18mg/kg 分为 6 等份，2 周内给药）和/或口服 6-姜酚（10mg/kg，给药前 5 天开始，持续至实验结束）处理。
6-姜酚显著改善了多柔比星引起的心脏酶升高。多柔比星刺激氧化应激的证据是血清可溶性晚期糖基化终产物受体的显著减少，导致未受抑制的血清晚期糖基化终产物的可用性。此外，多柔比星激活了核因子-κB（NF-κB），这表现为其在核中的免疫组化染色增加。此外，多柔比星诱导的心脏毒性伴随着心脏半胱氨酸天冬氨酸蛋白酶-3 的升高。值得注意的是，6-姜酚预处理显著改善了 sRAGE、NF-κB 和心脏半胱氨酸天冬氨酸蛋白酶-3 的变化。心脏酶与 NF-κB 和半胱氨酸天冬氨酸蛋白酶-3 呈显著正相关，与血清 sRAGE 呈负相关，表明它们在多柔比星诱导的心脏损伤中发挥作用。这些发现通过心脏组织病理学得到了证实。
6-姜酚，一种具有抗癌活性的姜的已知单一化合物，显示出在对抗多柔比星诱导的心脏毒性方面具有有前途的心脏保护作用。本研究提出了 6-姜酚心脏保护的一种新机制，可能通过其抗氧化作用和 NF-κB 以及细胞凋亡的调节来介导。
