Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Food Chem Toxicol. 2013 Sep;59:724-30. doi: 10.1016/j.fct.2013.07.022. Epub 2013 Jul 17.
Damage to DNA can lead to many different acute and chronic pathophysiological conditions, ranging from cancer to endothelial damage. The current study has been initiated to determine whether the flavonoid wogonin can attenuate etoposide-induced oxidative DNA damage and apoptosis in mouse bone marrow cells. We found that oral administration of wogonin before etoposide injection significantly attenuates etoposide-induced oxidative DNA damage and apoptosis in a dose dependent manner. Etoposide induced a significant down-regulation of mRNA expression of the OGG1 repair gene and marked biochemical alterations characteristic of oxidative DNA stress, including increased 8-OHdG, enhanced lipid peroxidation and reduction in reduced glutathione. Prior administration of wogonin ahead of etoposide challenge restored these altered parameters. Importantly, wogonin had no antagonizing effect on etoposide-induce topoisomerase-II inhibition. Conclusively, our study indicates that wogonin has a protective role in the abatement of etoposide-induced oxidative DNA damage and apoptosis in the bone marrow cells of mice via suppression of oxidative DNA stress and enhancing DNA repair through modulation of OGG1 repair gene expression. Therefore, wogonin can be a promising chemoprotective agent and might be useful to avert secondary leukemia and other drug-related cancers in cured cancer patients and medical personnel exposing to the potent carcinogen etoposide.
DNA 损伤可导致许多不同的急性和慢性病理生理状况，从癌症到内皮损伤。本研究旨在确定黄酮类化合物高良姜素是否能减轻依托泊苷诱导的小鼠骨髓细胞氧化 DNA 损伤和凋亡。我们发现，依托泊苷注射前给予高良姜素口服可显著减轻依托泊苷诱导的氧化 DNA 损伤和凋亡，且呈剂量依赖性。依托泊苷可显著下调 OGG1 修复基因的 mRNA 表达，并导致氧化 DNA 应激的特征性生化改变，包括 8-OHdG 增加、脂质过氧化增强和还原型谷胱甘肽减少。依托泊苷挑战前给予高良姜素可恢复这些改变的参数。重要的是，高良姜素对依托泊苷诱导的拓扑异构酶 II 抑制无拮抗作用。总之，我们的研究表明，高良姜素通过抑制氧化 DNA 应激和通过调节 OGG1 修复基因表达增强 DNA 修复，在减轻小鼠骨髓细胞中依托泊苷诱导的氧化 DNA 损伤和凋亡方面具有保护作用。因此，高良姜素可能是一种有前途的化学保护剂，对于避免已治愈癌症患者和接触强致癌剂依托泊苷的医务人员发生继发性白血病和其他与药物相关的癌症可能有用。
