Suppression of lipid hydroperoxide-induced oxidative damage to cellular DNA by esculetin
Suppression of lipid hydroperoxide-induced oxidative damage to cellular DNA by esculetin
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DOI：
10.1248/bpb.26.840
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发表时间：
2003-06-01
影响因子：
2
通讯作者：
Takabayashi, F
中科院分区：
文献类型：
--
作者：
Kaneko, T;Tahara, S;Takabayashi, F
据报道，亚油酸过氧化氢（LOOH）由于铁（III）离子共存，导致培养细胞中典型的DNA碱基氧化产物8-氧-7,8-二氢-2'-脱氧鸟苷（8-oxodG）含量增加。我们研究了香豆素是否能够抑制经LOOH和铁（III）离子处理的人二倍体成纤维细胞TIG-7细胞DNA中8-oxodG的形成。与esculletin（6,7-二羟基香豆素）共处理TIG-7细胞可显著抑制LOOH和铁（III）离子诱导的8-oxodG含量的增加。esculetin预处理细胞24 h也能有效保护细胞DNA免受随后用LOOH和铁（III）离子处理引起的氧化损伤。用esculin （escultin的6-葡糖苷）进行预处理是有效的，但效果较差。此外，通过测定5,5-二甲基-1-吡咯啉n-氧化物（DMPO）对羟基自由基自旋加合物形成的抑制作用，考察了香豆素和羟基肉桂酸的自由基清除活性。含有邻儿茶酚部分的化合物，如槲皮素、黄曲霉素和咖啡酸，显著降低了DMPO-OH自旋加合物的ESR信号强度。这些结果表明，槲皮素可以有效地保护细胞免受氧化应激引起的DNA损伤，而邻儿茶酚部分的存在对于抗活性氧的抗氧化活性是重要的。
Linoleic acid hydroperoxide (LOOH) has been reported to cause an increase in the content of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a typical oxidation product of DNA bases, in cultured cells due to coexisting iron(III) ion. We examined whether coumarins are able to suppress the formation of 8-oxodG in the DNA of human diploid fibroblasts, TIG-7 cells, treated with LOOH and iron(III) ion. Cotreatment of TIG-7 cells with esculetin (6,7-dihydroxycoumarin) significantly suppressed the increase in 8-oxodG content induced by LOOH and iron(III) ion. Pretreatment of cells with esculetin for 24 h was also effective in protecting cellular DNA against oxidative damage induced by subsequent treatment with LOOH and iron(III) ion. Pretreatment with esculin, the 6-glucoside of esculetin, was effective, but to a lesser extent. Furthermore, the free radical-scavenging activities of coumarins and hydroxycinnamic acids were examined by measuring the inhibition of spin-adduct formation of hydroxyl radicals with 5,5-dimethyl-1-pyrroline N-oxide (DMPO). Compounds bearing an ortho-catechol moiety, such as esculetin, fraxetin, and caffeic acid, significantly reduced the ESR signal intensities of the DMPO-OH spin adduct. These results indicate that esculetin is effective in protecting cells against DNA damage induced by oxidative stress and that the presence of an ortho-catechol moiety is important for antioxidant activities against reactive oxygen species.