title: Inhibition of nitric oxide and reactive oxygen species production improves the ability of a sunscreen to protect from sunburn, immunosuppression and photocarcinogenesis.
abstract: BACKGROUND
  More effective strategies are required for the prevention of skin cancer, which is caused by ultraviolet (UV) radiation in sunlight. Sunscreens containing UV filters or reflectors offer some protection from sunlight. Pharmacologically active compounds that reduce UV damage offer considerable potential for improving sunscreen formulations. However, few studies have investigated whether the addition of such biological modifiers are an improvement.
  
  
  OBJECTIVE
  In this study we supplemented a 2-ethyl hexyl methoxycinnamate-based sunscreen with the nitric oxide (NO) inhibitor NG-monomethyl-L-arginine acetate, the iron chelator 2,2'-dipyridyl, which reduces reactive oxygen species (ROS) production, or both. This was to determine whether inhibition of NO, ROS, or both could improve photoprotection by a sunscreen.
  
  
  METHODS
  These sunscreens were compared for photoprotection from sunburn, immunosuppression and skin carcinogenesis in mice. To observe additional photoprotection by the NO and ROS inhibitors, UV doses were used that exceeded the protective capacity of the sunscreen.
  
  
  RESULTS
  The combined inhibition of both NO and ROS production, but neither alone, increased sunscreen protection from sunburn and immunosuppression. Similarly, inhibition of both NO and ROS but neither alone reduced tumour multiplicity and incidence, therefore improving sunscreen protection from photocarcinogenesis.
  
  
  CONCLUSIONS
  Whether NO and ROS inhibition were independently improving sunscreen photoprotection, with both being required for an observable effect, or whether inhibition of an interaction between NO and ROS was responsible for improved photoprotection by the sunscreen is unknown. These studies show that supplementation of a sunscreen with inhibitors of NO and ROS production improves the ability of the sunscreen to protect from sunburn, immunosuppression and photocarcinogenesis. Such an approach may be useful for reducing skin cancer incidence in humans.
authors.affiliation: Discipline of Medicine (Dermatology), Melanoma and Skin Cancer Research Institute, Sydney Cancer Centre, Royal Prince Alfred Hospital, University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: P A J
authors.initials: PA
authors.lastname: Russo
authors.forename: G M
authors.initials: GM
authors.lastname: Halliday
mesh_terms: D015082:2,2'-Dipyridyl / Q000494:pharmacology; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D002614:Chelating Agents / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007108:Immune Tolerance / Q000187:drug effects*; D051379:Mice; D008812:Mice, Hairless; D009381:Neoplasms, Radiation-Induced / Q000378:metabolism / Q000517:prevention & control*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D012878:Skin Neoplasms / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D013471:Sunburn / Q000517:prevention & control*; D013473:Sunscreening Agents / Q000737:chemistry / Q000494:pharmacology*; D014466:Ultraviolet Rays / Q000009:adverse effects; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D002614:Chelating Agents; D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D013473:Sunscreening Agents; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D015082:2,2'-Dipyridyl