Protective effects of hydroxybenzoic acids and their esters on cell damage induced by hydroxyl radicals and hydrogen peroxides.
The purpose of this study was to evaluate the hydroxyl radical scavenging activities of hydroxybenzoic acids and their esters from both chemical and biological aspects. These activities of hydroxybenzoic acids and their related compounds were estimated by ESR-spin trapping method, in which 3,4,5-trihydroxybenzoic acid and its ethyl and propyl esters showed the highest activities as estimated by IC50 value (50% inhibition concentration of hydroxyl radicals generated in the system): 78.04 +/- 11.23, 95.95 +/- 2.64, and 86.46 +/- 2.31 microM, respectively. In addition, 3,4,5-trihydroxybenzoic acid (gallic acid) at a concentration of 25 microM, protected against dermal fibroblast cell damage induced by H2O2, and enhanced the survival to 83.8 +/- 3.1%, in which the survival of control was 44.2 +/- 1.0%. Based on these results, the pretreatment effects of 3,4,5-trihydroxybenzoic acid n-alkyl esters on cell damage induced by H2O2 were examined. The survival of fibroblasts pretreated with the esters increased depending on the alkyl chain-length. Both C12 and C16 alkyl esters gave almost complete cell survival of 89.5 +/- 2.0% and 91.3 +/- 1.0%, respectively. The order of the protective effects of the compounds was in good agreement with that of their partition coefficients, suggesting that 3,4,5-trihydroxybenzoic acid alkyl esters are incorporated into fibroblasts, and thus prevent the cells from the toxicity caused by H2O2. In addition, an increase of intracellular peroxide formation in fibroblasts induced by UVA-irradiation, was suppressed to 2.27 +/- 0.41 nmol/10(4) cells by pretreatment with C16 alkyl ester at a concentration of 25 microM. Since 3,4,5-trihydroxybenzoic group has been demonstrated to possess a potent scavenging activity of hydroxyl radicals, this moiety was indicated to be important in preventing cell damage induced by UVA or H2O2: in turn, these produce hydroxyl radicals in the presence of trace metal ions such as iron and copper in cells.
Masaki
H
H
Shiga Central Laboratories, Noevir Co., Ltd., Japan.
Okamoto
N
N
Sakaki
S
S
Sakurai
H
H
D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004578:Electron Spin Resonance Spectroscopy; D004952:Esters / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000528:radiation effects; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D062385:Hydroxybenzoates / Q000494:pharmacology*; D017665:Hydroxyl Radical / Q000378:metabolism*; D012867:Skin / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects; D014466:Ultraviolet Rays
D004952:Esters; D016166:Free Radical Scavengers; D062385:Hydroxybenzoates; D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide