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Evaluation of the efficacy and safety of antioxidant supplements on the basis of oxidative DNA damage profiles

基于氧化 DNA 损伤谱评估抗氧化剂补充剂的功效和安全性

基本信息

批准号：
17590528
负责人：
ITO Kimiko
金额：
$ 2.18万
依托单位：
Tsu City College
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

Oxidative stress has been implicated in the pathogenesis of various health disorders including cancer. It has been therefore suggested that antioxidant supplementation provides potential health benefits and disease prevention strategies by ameliorating oxidative stress. Particularly, antioxidants derived from dietary sources are now taken to the public widely, because they have very long history of use without any significant adverse effects. However, no conclusive evidence of the efficacy and safety of antioxidant supplements has been provided yet. Moreover, epidemiological studies demonstrated that β-carotene increased the incidences of lung cancer in smokers. This work was performed to systematically evaluate the beneficial and harmful effects of antioxidant supplements such as coenzyme Q10 (CoQ10) on human health. We found that UVA irradiation of CoQ10 induced damage to isolated DNA fragments obtained from human c-Ha-ras-1 protooncogene. The photosensitized DNA damage by CoQ10 was also observed in the presence of Cu(II) and the cleavage pattern was different from that induced in the absence of Cu(II). In addition, the reduced form of CoQ10 in the presence of Cu(II) increased the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a marker of oxidative DNA damage, in calf thymus DNA. The effect of CoQ10 supplementation on the urinary levels of 8-oxodG was also investigated in a cross-over study with 31 healthy volunteers. Participants received 3-weeks of CoQ10 (60 mg/ day) and the urinary 8-oxodG levels were measured by HPLC-ECD. The results revealed that the 8-oxodG level was significantly reduced in CoQ10 supplementation period compared to the control period (paired t-test, p<0.05).

氧化应激与包括癌症在内的各种健康疾病的发病机制有关。因此，抗氧化剂补充剂通过改善氧化应激提供了潜在的健康益处和疾病预防策略。特别是，从饮食中提取的抗氧化剂现在被广泛地向公众推广，因为它们有很长的使用历史，没有任何明显的副作用。然而，目前还没有确凿的证据证明抗氧化剂补充剂的有效性和安全性。此外，流行病学研究表明，β-胡萝卜素增加了吸烟者肺癌的发病率。本研究旨在系统评估辅酶Q10 （CoQ10）等抗氧化剂补充剂对人体健康的有益和有害影响。我们发现，CoQ10的UVA照射对从人c-Ha-ras-1原癌基因中获得的分离DNA片段造成损伤。在Cu（II）存在的情况下，CoQ10的光敏DNA损伤与Cu（II）不存在时不同。此外，CoQ10在Cu（II）存在下的还原形式增加了小牛胸腺DNA中8-氧-7,8-二氢-2'-脱氧鸟苷（8-oxodG）的形成，8-oxodG是氧化DNA损伤的标志。在一项与31名健康志愿者的交叉研究中，还研究了补充辅酶q10对尿中8-氧合物g水平的影响。参与者接受为期3周的辅酶q10（60毫克/天）治疗，并通过HPLC-ECD测量尿中8-oxodG水平。结果显示，与对照组相比，辅酶q10补充期8-oxodG水平显著降低（配对t检验，p<0.05）。