Wahab M H, Akoul E S, Abdel-Aziz A A
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Nasr City, Cairo, Egypt.
Tumori. 2000 Mar-Apr;86(2):157-62. doi: 10.1177/030089160008600210.
Doxorubicin (Dox), an anthracycline antibiotic, has a wide spectrum of antitumor activity with dose-limiting cardiotoxicity. The drug's toxicity is known to be closely related to the generation of active oxygen free radicals. In our study the normal cardiac tissue contents of total protein, glutathione (GSH) and malondialdehyde (MDA) were significantly decreased, by 25%, 33% and 92%, respectively, in the group of mice bearing Ehrlich ascites carcinoma (EAC) and treated with Dox (4 mg/kg/week x 2, ip). Administration of melatonin (5 mg/kg/day x 15, po) starting 24 hours prior to Dox treatment significantly increased the cardiac contents of total protein and GSH as well as the superoxide dismutase (SOD) activity, by 31%, 36% and 39%, respectively, compared to treatment with Dox only, while the content of MDA was decreased by 26%. Similarly, administration of vitamin E (250 mg/kg/day x 15, po) starting 24 hours prior to Dox treatment significantly increased the cardiac contents of total protein, GSH and SOD, by 23%, 26% and 42%, respectively, while the cardiac content of MDA was decreased by 35% compared with the Dox-only-treated group. As to the oncolytic activity of Dox, pretreatment of EAC-bearing mice with melatonin (5 mg/kg/day x 30, po) or vitamin E (250 mg/kg/day x 30, po) 24 hours prior to Dox administration (4 mg/kg/week x 4, ip) improved the antitumor activity of Dox as indicated by the increase in the average life span of the animals and the number of long-term survivors as well as the decrease in body weight loss induced by Dox treatment. It is clear from these results that administration of melatonin not only protects against the cardiotoxicity induced by Dox treatment but also enhances its antitumor activity to a more significant extent than does vitamin E.
阿霉素（Dox）是一种蒽环类抗生素，具有广泛的抗肿瘤活性，但存在剂量限制性心脏毒性。已知该药物的毒性与活性氧自由基的产生密切相关。在我们的研究中，接种艾氏腹水癌（EAC）并用Dox（4mg/kg/周×2，腹腔注射）治疗的小鼠组中，心脏组织总蛋白、谷胱甘肽（GSH）和丙二醛（MDA）的正常含量分别显著降低了25%、33%和92%。在Dox治疗前24小时开始给予褪黑素（5mg/kg/天×15，口服），与仅用Dox治疗相比，心脏总蛋白和GSH含量以及超氧化物歧化酶（SOD）活性分别显著增加了31%、36%和39%，而MDA含量降低了26%。同样，在Dox治疗前24小时开始给予维生素E（250mg/kg/天×15，口服），与仅用Dox治疗的组相比，心脏总蛋白、GSH和SOD含量分别显著增加了23%、26%和42%，而心脏MDA含量降低了35%。关于Dox的溶瘤活性，在给予Dox（4mg/kg/周×4，腹腔注射）前24小时，用褪黑素（5mg/kg/天×30，口服）或维生素E（250mg/kg/天×30，口服）对接种EAC的小鼠进行预处理，可改善Dox的抗肿瘤活性，表现为动物平均寿命延长、长期存活者数量增加以及Dox治疗引起的体重减轻减少。从这些结果可以清楚地看出，给予褪黑素不仅可以预防Dox治疗引起的心脏毒性，而且比维生素E更能显著增强其抗肿瘤活性。
