Department of Zoology, Biochemistry and Molecular Biology Laboratory, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
Indian J Pharmacol. 2012 May;44(3):308-13. doi: 10.4103/0253-7613.96299.
The objective of the present study is to find low dose of doxorubicin (DOX) with cancer preventive activity and to check the implication of this low dose of DOX on antioxidant defence system during lymphoma growth in mice, as the clinical utility of anthracycline anticancer drugs, especially DOX is limited by a progressive cardiotoxicity linked to mitochondrial damage.
We selected a dose of DOX (0.90 mg/kg body weight of mouse), which is about 20 folds lower than clinically used dose for cancer treatment. The cancer preventive action is monitored by modulation of anaerobic metabolism. The effect of this dose on antioxidant defence system is analyzed by testing the activities of antioxidant enzymes, such as catalase (CAT), superoxide dismutase (SOD), and glutathione S-transferase (GST). The activities of these enzymes were monitored at different intervals during the growth of lymphoma in mice.
The activities of antioxidant enzymes, such as CAT, SOD, and GST, were found to decrease gradually during the growth of lymphoma in mice. The anaerobic metabolism was increasing with lymphoma growth. We report that about 20 folds lower dose of DOX enhances the activities of antioxidant enzymes and decreases anaerobic metabolism during the development of lymphoma. These enzymes of antioxidant defence system suppress oxidative stress and mitochondrial damage, whereas a decrease in anaerobic metabolism checks cancer growth.
The result suggests that dose cumulative cellular toxicity of DOX may be avoided by treating cancer in animals with lower doses of DOX in combination with other drugs.
本研究的目的是寻找具有癌症预防活性的低剂量阿霉素（DOX），并检查这种低剂量 DOX 对小鼠淋巴瘤生长过程中抗氧化防御系统的影响，因为蒽环类抗癌药物的临床应用，尤其是 DOX，受到与线粒体损伤相关的进行性心脏毒性的限制。
我们选择了一个剂量的 DOX（0.90 毫克/千克小鼠体重），这大约是临床用于癌症治疗的剂量的 20 倍。通过调节无氧代谢来监测癌症预防作用。通过测试抗氧化酶（如过氧化氢酶（CAT）、超氧化物歧化酶（SOD）和谷胱甘肽 S-转移酶（GST））的活性来分析这种剂量对抗氧化防御系统的影响。在小鼠淋巴瘤生长的不同时间间隔监测这些酶的活性。
发现抗氧化酶（如 CAT、SOD 和 GST）的活性在小鼠淋巴瘤生长过程中逐渐下降。无氧代谢随着淋巴瘤的生长而增加。我们报告，大约 20 倍低剂量的 DOX 可增强抗氧化酶的活性，并在淋巴瘤发展过程中降低无氧代谢。这些抗氧化防御系统的酶抑制氧化应激和线粒体损伤，而无氧代谢的减少则抑制癌症的生长。
结果表明，通过用低剂量 DOX 联合其他药物治疗动物癌症，可以避免 DOX 的累积细胞毒性。
