Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, PO Box 2457, Riyadh, Saudi Arabia.
Food Chem Toxicol. 2012 May;50(5):1749-54. doi: 10.1016/j.fct.2012.02.092. Epub 2012 Mar 6.
The possible chemoprotective activity of theanine against irinotecan-induced genomic DNA damage towards mouse bone marrow cells was investigated. Chromosomal aberrations, DNA damage, micronuclei formation and mitotic activity were studied in the current study as markers of genomic damage. Oxidative DNA stress markers such as 8-hydroxydeoxyguanosine, lipid peroxidation, reduced and oxidized glutathione levels were assessed as a possible mechanism underlying this amelioration. Theanine was neither genotoxic nor cytotoxic in mice at doses equivalent to 30 or 60 mg/kg for 12 days. Pretreatment of mice with theanine significantly reduced irinotecan-induced genomic damage in the bone marrow cells and these effects were dose dependent. Irinotecan induced marked biochemical alterations characteristic of oxidative DNA stress, including increased 8-hydroxydeoxyguanosine, enhanced lipid peroxidation and reduction in the reduced/oxidized glutathione ratio. Prior administration of theanine ahead of irinotecan challenge ameliorated these oxidative DNA stress markers. Overall, this study provides for the first time that theanine has a protective role in the abatement of irinotecan-induced genomic damage in the bone marrow cells of mice that resides, at least in part, on its ability to modulate the cellular antioxidant levels and consequently protect bone marrow from irinotecan genotoxicity.
本研究旨在探讨茶氨酸对伊立替康诱导的小鼠骨髓细胞基因组 DNA 损伤的化学预防作用。在本研究中，染色体畸变、DNA 损伤、微核形成和有丝分裂活性被用作基因组损伤的标志物进行研究。氧化 DNA 应激标志物，如 8-羟基脱氧鸟苷、脂质过氧化、还原型和氧化型谷胱甘肽水平，被评估为这种改善的可能机制。在相当于 30 或 60mg/kg 的剂量下，茶氨酸连续 12 天处理小鼠，既没有遗传毒性也没有细胞毒性。用茶氨酸预处理小鼠可显著降低伊立替康诱导的骨髓细胞基因组损伤，且这种作用呈剂量依赖性。伊立替康诱导了特征性的氧化 DNA 应激的明显生化改变，包括 8-羟基脱氧鸟苷增加、脂质过氧化增强以及还原型/氧化型谷胱甘肽比值降低。在伊立替康攻击前给予茶氨酸可以改善这些氧化 DNA 应激标志物。总的来说，这项研究首次表明，茶氨酸在减轻伊立替康诱导的小鼠骨髓细胞基因组损伤方面具有保护作用，其作用至少部分在于其调节细胞抗氧化水平的能力，从而保护骨髓免受伊立替康的遗传毒性。
