Division of Radiobiology and Toxicology, Manipal Life Sciences Centre, Manipal University, Manipal 576104, Karnataka, India.
Mutagenesis. 2010 Nov;25(6):577-87. doi: 10.1093/mutage/geq043. Epub 2010 Aug 16.
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.
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。