title: Attenuation of UVA-induced damage to human keratinocytes by silymarin.
abstract: BACKGROUND
  UV radiation from sunlight is a potent environmental risk factor in skin cancer pathogenesis. UVA is the major portion of UV light reaching the earth surface ( approximately 95%) and it is reported to lead to benign and malignant tumor formation. UVA-mediated cellular damage occurs primarily through the release of reactive oxygen species (ROS) and it is responsible for inflammation, immunosuppression, photoaging and photocarcinogenesis.
  
  
  OBJECTIVE
  The aim of our study was to investigate the potency of silymarin, the polyphenol fraction from the seeds of Silybum marianum, to modulate UVA-induced oxidative damage to human keratinocytes.
  
  
  METHODS
  Skin epidermal cell line HaCaT, extensively used for studying the influence of UV radiation, was chosen as an experimental model. Silymarin's effect on UVA-disrupted cell viability, proliferation, mitochondrial function, and intracellular ATP and GSH level was measured. Furthermore, silymarin's potency to reduce UVA-induced ROS generation, membrane lipid peroxidation, caspase-3 activation and DNA damage was monitored.
  
  
  RESULTS
  Treatment of irradiated HaCaT (20 J/cm(2)) with silymarin (0.7-34 mg/l; 4h) resulted in concentration-dependent diminution of UVA-caused oxidative stress on all studied parameters. Silymarin application extensively reduced GSH depletion and ROS production as well as lipid peroxidation in irradiated cells. Formation of UVA-induced DNA single strand breaks and caspase-3 activity was also significantly decreased by silymarin.
  
  
  CONCLUSIONS
  The results suggest that silymarin may be beneficial in the treatment of UVA-induced skin oxidative injury and inflammation. However, further studies especially whose using human systems are needed to determine efficacy of silymarin in vivo.
authors.affiliation: Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University, Hnevotínská 3, 775 15 Olomouc, Czech Republic. alf.svoboda@seznam.cz
authors.forename: Alena
authors.initials: A
authors.lastname: Svobodová
authors.forename: Adéla
authors.initials: A
authors.lastname: Zdarilová
authors.forename: Jana
authors.initials: J
authors.lastname: Malisková
authors.forename: Hana
authors.initials: H
authors.lastname: Mikulková
authors.forename: Daniela
authors.initials: D
authors.lastname: Walterová
authors.forename: Jitka
authors.initials: J
authors.lastname: Vostalová
mesh_terms: D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000528:radiation effects; D012838:Silymarin / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D000975:Antioxidants; D012838:Silymarin