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尼姆泊酚在动物模型中对抗化疗药物羟基脲诱导的遗传和氧化损伤的保护作用。

Protective role of nimbolide against chemotherapeutic drug hydroxyurea induced genetic and oxidative damage in an animal model.

机构信息

Cytogenetics and Molecular Toxicological Laboratory, Section of Genetics, Department of Zoology, Aligarh Muslim University, Aligarh 202002, Uttar Pradesh, India.

Molecular Cancer Genetics & Translational Research Lab, Section of Genetics, Department of Zoology, Aligarh Muslim University, Aligarh 202002, Uttar Pradesh, India.

出版信息

Environ Toxicol Pharmacol. 2018 Jun;60:91-99. doi: 10.1016/j.etap.2018.04.006. Epub 2018 Apr 12.

Abstract

Nimbolide is known to be an antioxidant found in neem plant. Hydroxyurea is a medication frequently used in sickle-cell disease, different cancers and HIV infection. The present study aimed to evaluate the adverse effect of HU and possible amelioration by nimbolide in Wistar rats. To test our hypothesis, we performed genotoxicity tests, biochemical assays, and histopathological studies. We observed that HU caused higher levels of genotoxicity in the treated animals. The observed genetic and oxidative damage might be due to the presence of reactive species as HU increased the level of the malondialdehyde-a biomarker of oxidative damage. Interestingly, co-treatment of animals with HU and nimbolide showed a lower level of damage. We conclude that nimbolide significantly protects the cells from the adverse effect of HU and could be considered as a potential adjuvant for the patients under HU therapy.

摘要

尼姆泊酚是从印度楝树中提取的一种抗氧化剂。羟基脲是一种常用于镰状细胞病、不同癌症和 HIV 感染的药物。本研究旨在评估羟基脲的不良反应,以及尼姆泊酚对 Wistar 大鼠的可能改善作用。为了验证我们的假设,我们进行了遗传毒性试验、生化测定和组织病理学研究。结果发现,羟基脲处理的动物表现出更高水平的遗传毒性。观察到的遗传和氧化损伤可能是由于活性物质的存在,因为羟基脲增加了丙二醛的水平——一种氧化损伤的生物标志物。有趣的是,用羟基脲和尼姆泊酚共同处理动物显示出较低的损伤水平。我们的结论是,尼姆泊酚能显著保护细胞免受羟基脲的不良反应,可被认为是羟基脲治疗患者的一种潜在辅助药物。

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