Flavonolignans from Silybum marianum moderate UVA-induced oxidative damage to HaCaT keratinocytes.
BACKGROUND
UV radiation from sunlight is a very potent environmental risk factor in the pathogenesis of skin cancer. Exposure to UV light, especially the UVA part, provokes the generation of reactive oxygen species (ROS), which induce oxidative stress in exposed cells. Topical application of antioxidants is a successful strategy for protecting the skin against UV-caused oxidative damage.


OBJECTIVE
In this study, silybin (SB) and 2,3-dehydrosilybin (DS) (1-50 micromol/l), flavonolignan components of Silybum marianum, were tested for their ability to moderate UVA-induced damage.


METHODS
Human keratinocytes HaCaT were used as an appropriate experimental in vitro model, to monitor the effects of SB and DS on cell viability, proliferation, intracellular ATP and GSH level, ROS generation, membrane lipid peroxidation, caspase-3 activation and DNA damage.


RESULTS
Application of the flavonolignans (1-50 micromol/l) led to an increase in cell viability of irradiated (20 J/cm(2)) HaCaT keratinocytes. SB and DS also suppressed intracellular ATP and GSH depletion, ROS production and peroxidation of membrane lipids. UVA-induced caspases-3 activity/activation was suppressed by treatment with SB and DS. Lower concentrations of both compounds (10 micromol/l) significantly reduced cellular DNA single strand break formation.


CONCLUSIONS
Taken together, the results suggest that these flavonolignans suppress UVA-caused oxidative stress and may be useful in the treatment of UVA-induced skin damage.
Svobodová
Alena
A
Department of Medical Chemistry and Biochemistry, Palacký University, Hnevotínská 3, 775 15 Olomouc, Czech Republic. alf.svoboda@seznam.cz
Zdarilová
Adéla
A
Walterová
Daniela
D
Vostálová
Jitka
J
D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D053148:Caspase 3 / Q000378:metabolism; D002461:Cell Line, Transformed; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000528:radiation effects*; D015227:Lipid Peroxidation / Q000187:drug effects; D020944:Silybum marianum; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects*; D011832:Radiation Injuries / Q000517:prevention & control; D011837:Radiation-Protective Agents / Q000494:pharmacology / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology / Q000627:therapeutic use; D012867:Skin / Q000473:pathology / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects*
D000975:Antioxidants; D011837:Radiation-Protective Agents; D017382:Reactive Oxygen Species; D012838:Silymarin; D000077385:Silybin; D053148:Caspase 3