Protection against ultraviolet A-induced oxidative damage in normal human epidermal keratinocytes under post-menopausal conditions by an ultraviolet A-activated caged-iron chelator: a pilot study

Photodermatol Photoimmunol Photomed. 2011 Oct;27(5):231-5. doi: 10.1111/j.1600-0781.2011.00604.x.


Background/purpose: Human skin is constantly exposed to ultraviolet A (UVA), which can generate reactive oxygen species and cause iron release from ferritin, leading to oxidative damage in biomolecules. This is particularly true in post-menopausal skin due to an increase in iron as a result of menopause. As iron is generally released through desquamation, the skin becomes a main portal for the release of excess iron in this age group. In the present study, we examined a strategy for controlling UVA- and iron-induced oxidative stress in skin using a keratinocyte post-menopausal cellular model system.

Methods: Keratinocytes that had been cultured under normal or high-iron, low-estrogen conditions were treated with (2-nitrophenyl) ethyl pyridoxal isonicotinoyl hydrazone (2-PNE-PIH). 2-PNE-PIH is a caged-iron chelator that does not normally bind iron but can be activated by UVA radiation to bind iron. Following incubation with 2-PNE-PIH, the cells were exposed to 5 J/cm² UVA and then measured for changes in lipid peroxidation and ferritin levels.

Results: 2-PNE-PIH protected keratinocytes against UVA-induced lipid peroxidation and ferritin depletion. Further, 2-PNE-PIH was neither cytotoxic nor did it alter iron metabolism.

Conclusion: 2-PNE-PIH may be a useful deterrent against UVA-induced oxidative stress in post-menopausal women.

MeSH terms

  • Cell Line
  • Epidermis / metabolism*
  • Epidermis / pathology
  • Female
  • Ferritins / metabolism
  • Humans
  • Iron / metabolism*
  • Iron Chelating Agents / pharmacology*
  • Keratinocytes / metabolism*
  • Keratinocytes / pathology
  • Lipid Peroxidation* / drug effects
  • Lipid Peroxidation* / radiation effects
  • Middle Aged
  • Pilot Projects
  • Postmenopause / metabolism*
  • Ultraviolet Rays / adverse effects*


  • Iron Chelating Agents
  • Ferritins
  • Iron