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，有人建议补充抗氧化剂通过改善氧化应激来提供潜在的健康益处和疾病预防策略。特别是，来自饮食来源的抗氧化剂现在被广泛应用于公众，因为它们有很长的使用历史，没有任何显著的不良影响。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-胡萝卜素会增加吸烟者患肺癌的几率。本工作旨在系统评价辅酶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，经UVA照射的CoQ10对人原癌基因c-Ha-ras-1的DNA片段有损伤作用。在铜(II)存在时，CoQ10对DNA的光敏损伤作用与不存在铜(II)时不同。此外，在Cu2+存在下，CoQ10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DNA氧化损伤的标志。补充辅酶Q10对31名健康志愿者的尿8-oxodG水平的影响也进行了交叉研究。受试者服用辅酶Q10(60 mg/d)3周，用高效液相色谱-电子捕获检测器测定尿8-oxodG水平。结果表明，辅酶Q10补充期的8-oxodG水平显著低于对照组(配对t检验，p&lt；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).