Reduction of ultraviolet light-induced oxidative stress by amino acid-based iron chelators.
The generation of free radicals by ultraviolet (UV) light accelerates skin aging, which is known as photoaging. Cutaneous iron catalyzes the generation of free radicals. We designed novel antioxidants that suppressed the iron-catalyzed free radical generation and the ensuing UV-induced damage by mimicking the binding site of iron sequestering proteins. These antioxidants, N-(2-hydroxybenzyl)amino acids, were prepared by condensation of amino acids such as glycine and L-serine with salicylaldehyde and followed by catalytic reduction. The compounds formed a 2:1 complex to iron ion. These amino acid derivatives inhibited the iron-induced hydroxyl radical generation (the Fenton reaction). The compounds also suppressed UV-induced lipid peroxidation in murine dermal fibroblast homogenates. In addition, N-(2-hydroxybenzyl)-L-serine showed protective activity against UV-induced cytotoxicity in murine dermal fibroblasts. Desferrioxamine, a strong iron sequestering compound, was effective in inhibiting the Fenton reaction and the lipid peroxidation, but it was ineffective in protecting against UV-induced cytotoxicity. The results suggest that UV-induced oxidative stress can be reduced by these amino acid derivatives.
Kitazawa
M
M
AminoScience Laboratories, Ajinomoto Co., Inc., Suzuki-cho 1-1, Kawasaki-ku, Kawasaki, Kanagawa, Japan.
Iwasaki
K
K
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004578:Electron Spin Resonance Spectroscopy; D005290:Ferric Compounds / Q000737:chemistry; D005347:Fibroblasts / Q000187:drug effects / Q000528:radiation effects; D005998:Glycine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000737:chemistry; D066298:In Vitro Techniques; D007502:Iron Chelating Agents / Q000737:chemistry / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects* / Q000528:radiation effects; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology; D012694:Serine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D012867:Skin / Q000187:drug effects / Q000528:radiation effects; D013056:Spectrophotometry, Ultraviolet; D014466:Ultraviolet Rays
D000975:Antioxidants; D005290:Ferric Compounds; D007502:Iron Chelating Agents; C403765:N-(2-hydroxybenzyl)glycine; C403766:N-(2-hydroxybenzyl)serine; D010636:Phenols; D017665:Hydroxyl Radical; D012694:Serine; D005998:Glycine