摘要: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.
关键词:coumarin compound;oxidative DNA damage;lipid hydroperoxide;8-oxo-7,8-dihydro-2′-deoxyguanosine;radical scavenging;human diploid fibroblasts