Shruthi S, Shenoy K Bhasker
Department of Post Graduate Studies in Applied Zoology, Alva's College, Moodubidire, India.
Department of Applied Zoology, Mangalore University, Mangalagangothri, India.
Environ Toxicol. 2021 Jan;36(1):123-131. doi: 10.1002/tox.23018. Epub 2020 Sep 9.
Cyclophosphamide (CP) is a potent chemotherapeutic agent and is also known to interact with specific biological molecules and produce numerous side effects such as genotoxicity, neurotoxicity, reproductive toxicity and nephrotoxicity. CP induces genotoxicity by generating oxygen/nitrogen derived free radicals during chemotherapy and causes DNA damage. Hence, to overcome such side effects of chemotherapeutic agents antioxidants are recommended. Gallic acid (GA) a phenolic compound is commonly exists in variety of fruits and in many plants. In the present study, genoprotecive effects of GA against CP induced genotoxicity in Swiss albino mice were evaluated by using comet assay, bone marrow, and peripheral micronucleus (MN) assays. CP produced oxidative stress induced hepatic damage was assessed by estimating the activity of liver superoxide dismutase (SOD), reduced glutathione content (GSH), and also by examining the histological alterations induced by CP in hepatic tissue of mice. It was noticed that, GA pretreatment significantly reduced the frequency of MN and DNA strand breaks induced by CP. GA also protected the hepatic tissue against CP induced reactive oxygen species (ROS) mediated damage and was evident by increased levels of liver SOD and GSH. GA ameliorated the histological changes induced by CP in hepatic tissue. These findings suggest that, GA is a versatile antioxidant with promising protection against CP induced genotoxicity and hepatic damage in Swiss albino mice.
环磷酰胺（CP）是一种强效化疗药物，已知它会与特定生物分子相互作用，并产生多种副作用，如遗传毒性、神经毒性、生殖毒性和肾毒性。CP在化疗过程中通过产生氧/氮衍生的自由基诱导遗传毒性，并导致DNA损伤。因此，为了克服化疗药物的此类副作用，推荐使用抗氧化剂。没食子酸（GA）是一种酚类化合物，常见于多种水果和许多植物中。在本研究中，通过彗星试验、骨髓和外周血微核（MN）试验评估了GA对CP诱导的瑞士白化小鼠遗传毒性的基因保护作用。通过估计肝脏超氧化物歧化酶（SOD）的活性、还原型谷胱甘肽含量（GSH），以及检查CP在小鼠肝组织中诱导的组织学改变，评估了CP产生的氧化应激诱导的肝损伤。结果发现，GA预处理显著降低了CP诱导的MN频率和DNA链断裂。GA还保护肝组织免受CP诱导的活性氧（ROS）介导的损伤，这通过肝脏SOD和GSH水平的升高得以体现。GA改善了CP在肝组织中诱导的组织学变化。这些发现表明，GA是一种多功能抗氧化剂，对CP诱导的瑞士白化小鼠遗传毒性和肝损伤具有有前景的保护作用。
