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Mitigation of X-ray induced DNA damages and expression of DNA-repair genes by antioxidative Potentilla fulgens root extract and its ethyl-acetate fraction in mammalian cells
Mutagenesis ( IF 2.7 ) Pub Date : 2021-03-04 , DOI: 10.1093/mutage/geab009
Debabrata Tripathy 1 , Ravi Upadhyay 1 , Chongtham Sovachandra Singh 1 , Nabamita Boruah 1 , Nripendranath Mandal 2 , Anupam Chatterjee 1
Affiliation  

Potentilla fulgens is a medicinal plant in North-East India whose root is reported to have anti-diabetic, anticarcinogenic and antioxidant properties. The potential of hydro-alcoholic extract of P. fulgens root (PRE) for providing protection to mammalian cells exposed to ionising radiation was investigated in this study. The methanolic extract of PRE shows an enhanced radical scavenging ability in a concentration dependent manner. PRE-pre-treatment to stimulated human blood lymphocytes (HBLs) reduced the frequency of deletion and exchange aberrations induced by X-irradiation. Similar protection of chromosome aberrations was also observed in mouse bone marrow cells (BMCs) where mice were given PRE extract (1 mg extract/day/mice) ad libitum in the drinking water for 45 days before whole-body X-irradiation. Of the various extracts prepared by partitioning of the methanol extract, the ethyl-acetate (EA) fraction was found to possess better antioxidant, radical scavenging and DNA-damage reduction activities. PRE-pre-treatment also reduced the radiation-induced cell-cycle delay effectively in HBL. In HEK-293 cells, PRE reduced radiation-induced G2-block in cell kinetics. Interestingly, PRE-treatment alone increased the concentration of endogenous glutathione (GSH) in mouse BMC and in stimulated HBL along with the elevated expression of γ-glutamyl-cysteine synthetase heavy/catalytic subunit, a key determinant of GSH synthesis. Studies on expression of two DNA-repair genes revealed that there was a marked increase in the expression of GADD45 and H2AX genes after X-irradiation in stimulated HBL, and such expression was reduced significantly if PRE-treatment was given prior to radiation. The present findings show the ability of PRE to reduce radiation-induced DNA damages probably by free radical scavenging whereas modulation of expression of DNA-repair genes’ and endogenous GSH-increment emerge as effective strategies. The present study is the first report on the selected medicinal plant species that suggests it to be a potential natural radioprotector when used as root extract or its EA fraction for mitigating radiation toxicity.

中文翻译:

哺乳动物细胞中抗氧化委陵菜根提取物及其乙酸乙酯部分减轻 X 射线诱导的 DNA 损伤和 DNA 修复基因的表达

Potentilla fulgens 是印度东北部的一种药用植物,据报道其根具有抗糖尿病、抗癌和抗氧化特性。本研究调查了 P. fulgens 根的水醇提取物 (PRE) 为暴露于电离辐射的哺乳动物细胞提供保护的潜力。PRE 的甲醇提取物以浓度依赖性方式显示出增强的自由基清除能力。对受刺激的人血淋巴细胞 (HBL) 进行预预处理降低了 X 辐照引起的缺失和交换畸变的频率。在小鼠骨髓细胞 (BMC) 中也观察到对染色体畸变的类似保护,在小鼠骨髓细胞 (BMC) 中,小鼠在进行全身 X 射线照射前 45 天在饮用水中随意给予 PRE 提取物(1 mg 提取物/天/小鼠)。在通过分配甲醇提取物制备的各种提取物中,发现乙酸乙酯 (EA) 部分具有更好的抗氧化、自由基清除和 DNA 损伤减少活性。PRE 预处理还有效地减少了 HBL 中辐射诱导的细胞周期延迟。在 HEK-293 细胞中,PRE 减少了细胞动力学中辐射诱导的 G2 阻滞。有趣的是,单独的预处理增加了小鼠 BMC 和受刺激的 HBL 中内源性谷胱甘肽 (GSH) 的浓度,同时增加了 γ-谷氨酰-半胱氨酸合成酶重/催化亚基的表达,这是 GSH 合成的关键决定因素。对两个 DNA 修复基因表达的研究表明,在受激 HBL 中 X 射线照射后 GADD45 和 H2AX 基因的表达显着增加,如果在放射前给予预处理,这种表达会显着降低。目前的研究结果表明,PRE 可能通过清除自由基来减少辐射引起的 DNA 损伤,而调节 DNA 修复基因的表达和内源性 GSH 增加成为有效的策略。本研究是关于选定药用植物物种的第一份报告,表明当用作根提取物或其 EA 部分以减轻辐射毒性时,它是一种潜在的天然辐射防护剂。
更新日期:2021-03-04
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