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生物查尔酮 A 对γ射线诱导的氧化应激、抗氧化状态、凋亡和 DNA 修复分子的保护作用在瑞士白化小鼠中。

Protective Effect of Biochanin A on Gamma Radiation-Induced Oxidative Stress, Antioxidant Status, Apoptotic, and DNA Repairing Molecules in Swiss Albino Mice.

机构信息

The First Central Clinical School, Tianjin Medical University, Tianjin, China.

Department of Nuclear Medicine, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

出版信息

Cell Biochem Funct. 2024 Dec;42(8):e70005. doi: 10.1002/cbf.70005.

Abstract

Radiation therapy is indispensable in medical practice but often causes adverse effects on healthy tissues, necessitating the search for natural radioprotectors. This study investigates the protective effect of Biochanin A (BCA) against gamma radiation-induced oxidative stress and DNA damage in Swiss albino mice. Gamma radiation, a potent ionizing source, generates reactive oxygen species (ROS) that damage cellular biomolecules, including DNA. Antioxidants play a crucial role in neutralizing ROS and preventing oxidative damage. Swiss albino mice were divided into control, BCA control (10 mg/kg body weight), radiation alone (7 Gy), and radiation+ BCA pretreatment groups. BCA, a natural isoflavone with known antioxidant and cytoprotective properties, was administered intraperitoneally before radiation exposure. After irradiation, lipid peroxidation levels, antioxidant enzyme activities/level (superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione), expression levels of DNA repair genes (P53, P21, GADD45α), apoptotic markers (Bax, Bcl-2, Caspase-3, -9 and Cytochrome-C), and inflammatory marker (NF-κB) were analyzed in small intestine tissue. Our findings indicate that gamma radiation significantly elevated lipid peroxidation levels and altered antioxidant enzyme activities, indicating oxidative stress. However, BCA pretreatment mitigated these effects by bolstering antioxidant defences, reducing radiation-induced oxidative damage. Additionally, BCA altered apoptotic markers, NF-κB expression, promoting cell survival mechanisms. At the molecular level, BCA pretreatment upregulated key DNA repair genes (P53, P21, GADD45α), crucial for repairing radiation-induced DNA damage and maintaining genomic stability. These results underscore BCA potential as a radioprotector, suggesting its efficacy in mitigating radiation-induced oxidative stress and preserving cellular integrity. In conclusion, BCA demonstrates promising radioprotective properties by attenuating oxidative stress, enhancing antioxidant defences, modulating apoptotic pathways, and promoting DNA repair mechanisms following gamma radiation exposure. Further research is necessary to elucidate its precise mechanisms of action and explore its potential therapeutic applications in radiation oncology and environmental radioprotection.

摘要

放射治疗在医学实践中不可或缺,但往往会对健康组织产生不良反应,因此需要寻找天然的辐射防护剂。本研究旨在探讨大豆苷元(BCA)对γ射线诱导的瑞士白化小鼠氧化应激和 DNA 损伤的保护作用。γ射线是一种有效的电离源,会产生活性氧(ROS),破坏包括 DNA 在内的细胞生物分子。抗氧化剂在中和 ROS 和防止氧化损伤方面发挥着关键作用。瑞士白化小鼠被分为对照组、BCA 对照组(10mg/kg 体重)、单纯照射组(7Gy)和照射+BCA 预处理组。BCA 是一种具有已知抗氧化和细胞保护特性的天然异黄酮,在照射前通过腹腔内给药。照射后,分析小肠组织中的脂质过氧化水平、抗氧化酶活性/水平(超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶和还原型谷胱甘肽)、DNA 修复基因(P53、P21、GADD45α)的表达水平、凋亡标志物(Bax、Bcl-2、Caspase-3、-9 和 Cytochrome-C)和炎症标志物(NF-κB)。我们的研究结果表明,γ射线显著提高了脂质过氧化水平并改变了抗氧化酶的活性,表明发生了氧化应激。然而,BCA 预处理通过增强抗氧化防御来减轻这些影响,从而减少辐射引起的氧化损伤。此外,BCA 改变了凋亡标志物、NF-κB 的表达,促进了细胞存活机制。在分子水平上,BCA 预处理上调了关键的 DNA 修复基因(P53、P21、GADD45α),这些基因对于修复辐射诱导的 DNA 损伤和维持基因组稳定性至关重要。这些结果强调了 BCA 作为辐射防护剂的潜力,表明其在减轻辐射引起的氧化应激和保护细胞完整性方面的功效。总之,BCA 通过减轻氧化应激、增强抗氧化防御、调节凋亡途径和促进 DNA 修复机制,在 γ 射线照射后显示出有希望的辐射防护特性。需要进一步的研究来阐明其确切的作用机制,并探索其在放射肿瘤学和环境辐射防护中的潜在治疗应用。

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