Suppression of lipid hydroperoxide-induced oxidative damage to cellular DNA by esculetin

Biol Pharm Bull. 2003 Jun;26(6):840-4. doi: 10.1248/bpb.26.840.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Antioxidants / pharmacology*
  • Cations / toxicity
  • Cell Line
  • DNA Damage / drug effects*
  • Deoxyguanosine / analogs & derivatives*
  • Deoxyguanosine / analysis
  • Esculin / pharmacology
  • Ferric Compounds / toxicity
  • Humans
  • Hydroxyl Radical / metabolism
  • Linoleic Acids / toxicity*
  • Lipid Peroxides / toxicity*
  • Oxidative Stress / drug effects*
  • Umbelliferones / pharmacology*


  • Antioxidants
  • Cations
  • Ferric Compounds
  • Linoleic Acids
  • Lipid Peroxides
  • Umbelliferones
  • Esculin
  • linoleic acid hydroperoxide
  • Hydroxyl Radical
  • 8-Hydroxy-2'-Deoxyguanosine
  • Deoxyguanosine
  • esculetin