Kovary K, Louvain T S, Costa e Silva M C, Albano F, Pires B B, Laranja G A, Lage C L, Felzenszwalb I
Departamento de Bioquímica, Departamento de Biofísica e Biometria, Instituto de Biologia Roberto Alcântara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brasil.
Br J Nutr. 2001 Apr;85(4):431-40. doi: 10.1079/bjn2000287.
Naturally occurring antioxidants such as carotenoids are extensively studied for their potential in reducing the risk for cancer and other chronic diseases. In the present study, the radical-scavenger activity of the food additive norbixin, a water-soluble carotenoid extracted from Bixa orellana seeds and commercialized as annatto, was evaluated under conditions of DNA damage induced by reactive oxygen species, particularly by hydroxyl radicals. The cell-free scavenger activity of norbixin was evaluated using plasmid DNA as target molecule and Sn2+ or Fe2+ as oxidant. The addition of H2O2 enhanced DNA breakage induced by metal ions, particularly Fe2+. Under these conditions, norbixin started to protect plasmid DNA against single- and double-strand breakage at a metal:norbixin ratio of 1:1 (Sn2+) and 1:10 (Fe2+). However, at lower ratios to Sn2+, norbixin enhanced Sn2+-induced DNA breakage (P < 0.05). The ability of norbixin to protect genomic DNA against oxidative damage was assessed in murine fibroblasts submitted to H2O2-induced oxidative stress and the results were evaluated by the comet assay. Under low serum conditions (2 % fetal bovine serum (FBS)), a protective effect of norbixin against H2O2-induced DNA breakage was inversely related to its concentration, a protection ranging from 41 % (10 microm) to 21 % (50 microm). At higher concentrations of norbixin, however, oxidative DNA breakage was still enhanced, even in the presence of a high serum concentration (10 % FBS). Under normal conditions, norbixin per se has no detectable genotoxic or cytotoxic effects on murine fibroblasts. The antimutagenic potential of norbixin against oxidative mutagens was also evaluated by the Salmonella typhimurium assay, with a maximum inhibition of 87 % against the mutagenicity induced by H2O2. Although plasmid DNA and Ames data indicated that norbixin can protect DNA against oxidative damage, it seems to be a risky guardian of genomic DNA as it can also increase the extent of oxidative damage.
天然存在的抗氧化剂，如类胡萝卜素，因其在降低癌症和其他慢性疾病风险方面的潜力而受到广泛研究。在本研究中，对食品添加剂降红木素（一种从红木种子中提取并作为胭脂树橙商业化的水溶性类胡萝卜素）在活性氧特别是羟基自由基诱导的DNA损伤条件下的自由基清除活性进行了评估。以质粒DNA为靶分子，以Sn2+或Fe2+为氧化剂，评估了降红木素的无细胞清除活性。添加H2O2增强了金属离子特别是Fe2+诱导的DNA断裂。在这些条件下，降红木素在金属与降红木素的比例为1:1（Sn2+）和1:10（Fe2+）时开始保护质粒DNA免受单链和双链断裂。然而，在与Sn2+的比例较低时，降红木素增强了Sn2+诱导的DNA断裂（P<0.05）。在遭受H2O2诱导的氧化应激的小鼠成纤维细胞中评估了降红木素保护基因组DNA免受氧化损伤的能力，并通过彗星试验评估结果。在低血清条件（2%胎牛血清（FBS））下，降红木素对H2O2诱导的DNA断裂的保护作用与其浓度呈负相关，保护范围从41%（10微摩尔）到21%（50微摩尔）。然而，在降红木素浓度较高时，即使存在高血清浓度（10%FBS），氧化DNA断裂仍会增强。在正常条件下，降红木素本身对小鼠成纤维细胞没有可检测到的遗传毒性或细胞毒性作用。还通过鼠伤寒沙门氏菌试验评估了降红木素对氧化诱变剂的抗诱变潜力，对H2O2诱导的诱变的最大抑制率为87%。尽管质粒DNA和Ames试验数据表明降红木素可以保护DNA免受氧化损伤，但它似乎是基因组DNA的一个有风险的守护者，因为它也会增加氧化损伤的程度。
