Suppression of lipid hydroperoxide-induced oxidative damage to cellular DNA by esculetin.
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.
Kaneko
Takao
T
Redox Regulation Research Group, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakaecho, Itabashi-ku, Tokyo 173-0015, Japan. kaneko@tmig.or.jp
Tahara
Shoichi
S
Takabayashi
Fumiyo
F
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000975:Antioxidants / Q000494:pharmacology*; D002412:Cations / Q000633:toxicity; D002460:Cell Line; D004249:DNA Damage / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis; D004929:Esculin / Q000494:pharmacology; D005290:Ferric Compounds / Q000633:toxicity; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism; D008041:Linoleic Acids / Q000633:toxicity*; D008054:Lipid Peroxides / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D014468:Umbelliferones / Q000494:pharmacology*
D000975:Antioxidants; D002412:Cations; D005290:Ferric Compounds; D008041:Linoleic Acids; D008054:Lipid Peroxides; D014468:Umbelliferones; D004929:Esculin; C008285:linoleic acid hydroperoxide; D017665:Hydroxyl Radical; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; C007628:esculetin