Abdel-Raheem Ihab T, Abdel-Ghany Ahmed A
The Department of Pharmacology & Toxicology, Al-Azhar University, Assiut, Egypt.
J Egypt Natl Canc Inst. 2009 Jun;21(2):175-84.
Doxorubicin (DOX) is a potent chemotherapeutic agent used in the treatment of several tumors but its cardiac toxicity prevents its use at a maximum dose, representing an important problem. Increased reactive oxygen species (ROS) and imbalance in nitric oxide (NO) production have been implicated in the cardiotoxicity of doxorubicin. Hesperidin is a citrus bioflavonoid that possesses a potent antioxidant and NO modulating activities.
Therefore, the aim of this study was to investigate the possible protective role of hesperidin against doxorubicin-induced cardiac toxicity.
Four groups of animals were used in this study. First group served as a control and injected with the vehicle. Second group was given 200 mg/kg of hesperidin orally for seven consecutive days. The third group was injected with a single dose (20 mg/kg) of doxorubicin intraperitoneally and was sacrificed after 48 h. The fourth group was treated with hesperidin for seven days but on day five, 1-hour after hesperidin treatment, rats were injected with the single dose of doxorubicin. On day seven, the rats were scarified by decapitation. Blood was collected and processed for determination of serum lactate dehydrogenase (LDH), creatine kinase (CK) and NO. The hearts were removed and processed for both histopathological examination and determination of oxidative stress parameters like reduced glutathione (GSH), lipid peroxide (TBARS) levels and superoxide dismutase (SOD) activity.
Our results showed that doxorubicin produced severe cardiotoxicity as indicated from increase in serum LDH, CK activities and NO level. Histopathological examination of DOX-treated rats revealed degenerative changes in heart tissues. The significant decrease in GSH levels, SOD activity and increase in TBARS levels, indicated that DOX-induced cardiotoxicity was mediated through ROS generation. On the other hand, pretreatment of rats with hesperidin protected cardiac tissues against the cardiotoxic effects of doxorubicin as evidenced from amelioration of histopathological changes and normalization of cardiac biochemical parameters.
Hesperidin may have a protective effect against DOX-induced cardiotoxicity.
阿霉素（DOX）是一种用于治疗多种肿瘤的强效化疗药物，但其心脏毒性限制了其最大剂量的使用，这是一个重要问题。活性氧（ROS）增加和一氧化氮（NO）生成失衡与阿霉素的心脏毒性有关。橙皮苷是一种柑橘生物类黄酮，具有强大的抗氧化和NO调节活性。
因此，本研究旨在探讨橙皮苷对阿霉素诱导的心脏毒性可能的保护作用。
本研究使用了四组动物。第一组作为对照组，注射赋形剂。第二组连续七天口服200mg/kg橙皮苷。第三组腹腔注射单剂量（20mg/kg）阿霉素，并在48小时后处死。第四组用橙皮苷治疗七天，但在第五天，橙皮苷治疗1小时后，给大鼠注射单剂量阿霉素。在第七天，通过断头处死大鼠。采集血液并进行处理，以测定血清乳酸脱氢酶（LDH）、肌酸激酶（CK）和NO。取出心脏并进行处理，用于组织病理学检查以及测定氧化应激参数，如还原型谷胱甘肽（GSH）、脂质过氧化物（TBARS）水平和超氧化物歧化酶（SOD）活性。
我们的结果表明，阿霉素产生了严重的心脏毒性，血清LDH、CK活性和NO水平升高表明了这一点。对阿霉素处理的大鼠进行组织病理学检查发现心脏组织有退行性变化。GSH水平、SOD活性显著降低以及TBARS水平升高，表明阿霉素诱导的心脏毒性是通过ROS生成介导的。另一方面，用橙皮苷预处理大鼠可保护心脏组织免受阿霉素的心脏毒性作用，组织病理学变化的改善和心脏生化参数的正常化证明了这一点。
橙皮苷可能对阿霉素诱导的心脏毒性具有保护作用。
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