Ahmed Hanaa H, Mannaa Fathia, Elmegeed Gamal A, Doss Senot H
Hormones Department, National Research Centre, Dokki, Giza, Egypt.
Bioorg Med Chem. 2005 Mar 1;13(5):1847-57. doi: 10.1016/j.bmc.2004.10.066.
This study aimed at evaluation of melatonin and some of its novel synthesized derivatives 3, 4, 9 and 10b as cardioprotective agents against doxorubicin-induced acute cardiac toxicity in rats. Also, this work was extended to study the potential role of each synthesized derivative in comparison with the parent compound melatonin. Intraperitoneal injection of a single dose (15mg/kg B.W.) of doxorubicin resulted in significant increase in serum troponin I, leptin, triglycerides, cholesterol and LDL-cholesterol levels with concomitant decrease in serum T(3), T(4) and IL-1alpha levels. In contrast, intraperitoneal injection of melatonin or its synthesized derivatives especially compounds 3 and 10b in a dose of 5mg/kg B.W./day for 10days reversed doxorubicin-induced changes in the above mentioned parameters towards the normal values. The present data revealed that doxorubicin exerts its action mainly through the oxidative stress. This appeared from the significant elevation in serum nitric oxide level and cardiac lipid peroxidation level with concomitant decrease in cardiac antioxidative enzymes activity. Treatment with melatonin and its derivatives 3 and 10b could reduce the markers of oxidative stress and restore the activity of the antioxidative enzymes in the heart tissue. In conclusion, the cardioprotective effect of melatonin and its derivatives may be mediated through the antioxidant and free radical scavenging activity of these compounds.
本研究旨在评估褪黑素及其一些新合成衍生物3、4、9和10b作为心脏保护剂对阿霉素诱导的大鼠急性心脏毒性的作用。此外，本研究还扩展到比较每种合成衍生物与母体化合物褪黑素的潜在作用。腹腔注射单剂量（15mg/kg体重）阿霉素导致血清肌钙蛋白I、瘦素、甘油三酯、胆固醇和低密度脂蛋白胆固醇水平显著升高，同时血清T(3)、T(4)和IL-1α水平降低。相反，腹腔注射褪黑素或其合成衍生物，特别是化合物3和10b，剂量为5mg/kg体重/天，连续10天，可使阿霉素诱导的上述参数变化恢复到正常值。目前的数据表明，阿霉素主要通过氧化应激发挥作用。这表现为血清一氧化氮水平和心脏脂质过氧化水平显著升高，同时心脏抗氧化酶活性降低。用褪黑素及其衍生物3和10b治疗可降低氧化应激标志物，并恢复心脏组织中抗氧化酶的活性。总之，褪黑素及其衍生物的心脏保护作用可能是通过这些化合物的抗氧化和自由基清除活性介导的。
