Zarei Mahsa, Shivanandappa T
J Basic Clin Physiol Pharmacol. 2016 Jun 1;27(4):341-8. doi: 10.1515/jbcpp-2015-0114.
Cyclophosphamide (CP), one of the most widely used antineoplastic drugs, causes toxic side effects on vital organs including brain. In this study, we have investigated neuroprotective potential of the aqueous extract of the roots of Decalepis hamiltonii (DHA) against CP-induced oxidative stress in the mouse brain.
Swiss albino male mice were pre-treated with DHA (50 and 100 mg/kg b.w.) for 10 consecutive days followed by an injection with CP intraperitoneally (25 mg/kg b.w.) for 10 days 1 h after DHA treatment; 16 h later, they were euthanized, their brains were immediately removed, and biochemical and molecular analyses were conducted.
The results indicated that injection of CP induced oxidative stress in the mouse brain as evident from the increased lipid peroxidation, reactive oxygen species, depletion of glutathione and reduced activities of the antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase. Treatment with DHA significantly mitigated the CP-induced oxidative stress. Moreover, expression of genes for the antioxidant enzymes was downregulated by CP treatment which was reversed by DHA.
In conclusion, DHA protected the brain from oxidative stress induced by CP, and therefore, it could be a promising nutraceutical as a supplement in cancer chemotherapy in order to ameliorate the toxic side effects of cancer drugs.
环磷酰胺(CP)是最广泛使用的抗肿瘤药物之一,会对包括大脑在内的重要器官产生毒副作用。在本研究中,我们研究了汉氏马兜铃根水提取物(DHA)对CP诱导的小鼠脑氧化应激的神经保护潜力。
将瑞士白化雄性小鼠连续10天用DHA(50和100毫克/千克体重)预处理,然后在DHA处理1小时后腹腔注射CP(25毫克/千克体重),持续10天;16小时后,将它们安乐死,立即取出大脑,并进行生化和分子分析。
结果表明,注射CP可诱导小鼠脑氧化应激,脂质过氧化增加、活性氧增加、谷胱甘肽耗竭以及超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶、谷胱甘肽还原酶和谷胱甘肽-S-转移酶等抗氧化酶活性降低均证明了这一点。用DHA处理可显著减轻CP诱导的氧化应激。此外,CP处理下调了抗氧化酶基因的表达,而DHA可逆转这种下调。
总之,DHA保护大脑免受CP诱导的氧化应激,因此,作为癌症化疗中的补充剂,它可能是一种有前景的营养保健品,以改善抗癌药物的毒副作用。