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姜酮,一种酚烷酮,对体外培养的中国仓鼠肺成纤维细胞的辐射诱导的细胞毒性、遗传毒性、细胞凋亡和氧化应激具有拮抗作用。

Antagonistic effects of Zingerone, a phenolic alkanone against radiation-induced cytotoxicity, genotoxicity, apoptosis and oxidative stress in Chinese hamster lung fibroblast cells growing in vitro.

机构信息

Division of Radiobiology and Toxicology, Manipal Life Sciences Centre, Manipal University, Manipal 576104, Karnataka, India.

出版信息

Mutagenesis. 2010 Nov;25(6):577-87. doi: 10.1093/mutage/geq043. Epub 2010 Aug 16.

Abstract

Zingerone (ZO), a dietary phenolic compound was investigated for its ability to protect against radiation-induced oxidative stress and DNA damage in Chinese hamster fibroblast cells (V79). Cells treated with optimal dose of ZO (25 μg/ml), 1 h prior radiation exposure resulted in a significant (P<0.01) elevation of cell survival and decreased the genotoxicity (micronuclei and comet assays). Further, pretreatment with ZO significantly reduced radiation-induced oxidative stress as indicated by decreased reactive oxygen species levels and inhibition of mitochondrial depolarisation. The experiments conducted to evaluate the intracellular antioxidant activity in ZO-pretreated cells demonstrated a significant (P<0.01) increase in the various antioxidants like glutathione, gluthione-S-transferase, superoxide dismutase, catalase and a significant (P<0.01) decrease in malondialdehyde levels versus irradiation alone. Further, ZO scavenged various free radicals generated in vitro (OH·, O(2)·, DPPH·, ABTS·(+) and NO·) in a dose-dependent manner. The anti-apoptotic effect of ZO pretreatment was by the inhibition of the activation of capase-3, by upregulating Bcl-2 and down-regulating Bax proteins. Our study demonstrates the antagonistic effect of ZO against radiation-induced cytotoxicity. Further, ZO rendered anti-genotoxic, anti-apoptotic and anti-lipid peroxidative potency, plausibly ascribable to its antioxidant/free radical scavenging ability and also by the suppression of radiation-induced oxidative stress.

摘要

荜澄茄酮(ZO),一种膳食酚类化合物,其研究旨在探讨其是否具有抵抗辐射诱导的氧化应激和 DNA 损伤的能力,研究对象为中国仓鼠成纤维细胞(V79)。细胞经 ZO 最佳剂量(25μg/ml)预处理 1 小时后再进行辐射暴露,结果显示细胞存活率显著提高(P<0.01),同时细胞的遗传毒性(微核和彗星试验)降低。此外,ZO 预处理还可显著降低辐射诱导的氧化应激,这表现为活性氧水平降低和线粒体去极化抑制。通过评价 ZO 预处理细胞的细胞内抗氧化活性的实验,我们发现细胞内各种抗氧化剂(如谷胱甘肽、谷胱甘肽 S-转移酶、超氧化物歧化酶、过氧化氢酶)的含量显著增加(P<0.01),同时丙二醛水平显著降低(P<0.01),与单独辐射相比。此外,ZO 还可清除体外生成的各种自由基(OH·、O(2)·、DPPH·、ABTS·(+)和 NO·),且这种清除作用具有剂量依赖性。ZO 预处理的抗细胞凋亡作用是通过抑制半胱天冬酶-3 的激活,上调 Bcl-2 并下调 Bax 蛋白来实现的。我们的研究表明,ZO 对辐射诱导的细胞毒性具有拮抗作用。此外,ZO 还具有抗遗传毒性、抗细胞凋亡和抗脂质过氧化作用,这可能归因于其抗氧化/自由基清除能力,以及对辐射诱导的氧化应激的抑制作用。

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