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

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，已经表明，抗氧化剂补充剂通过改善氧化应激提供潜在的健康益处和疾病预防策略。特别是，来自膳食来源的抗氧化剂现在被广泛用于公众，因为它们具有很长的使用历史，没有任何显著的不良影响。然而，还没有提供抗氧化剂补充剂的有效性和安全性的结论性证据。此外，流行病学研究表明，β-胡萝卜素增加吸烟者肺癌的发病率。这项工作是为了系统地评估抗氧化剂补充剂如辅酶Q10（CoQ10）对人体健康的有益和有害影响。我们发现，UVA照射辅酶Q10诱导损伤的分离的DNA片段从人c-Ha-ras-1原癌基因。在Cu（II）存在下也观察到CoQ10的光敏DNA损伤，并且切割模式不同于在没有Cu（II）存在下诱导的切割模式。此外，还原形式的辅酶Q10在Cu（II）的存在下增加了8-氧代-7，8-二氢-2'-脱氧鸟苷（8-oxodG）的形成，这是小牛胸腺DNA中氧化性DNA损伤的标志物。辅酶Q10补充剂对8-oxodG尿液水平的影响也在31名健康志愿者的交叉研究中进行了研究。参与者接受3周的CoQ10（60 mg/天），并通过HPLC-ECD测量尿8-oxodG水平。结果显示，与对照期相比，补充CoQ10期间的8-oxodG水平显著降低（配对t检验，p <0.05）。

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).