title: Cocaine induces oxidative damage to skin via xanthine oxidase and nitric oxide synthase.
abstract: BACKGROUND
  Heavy cocaine abusers are known to develop adverse skin manifestations, however, a possible mechanism for such damages has not yet been proposed.
  
  
  OBJECTIVE
  The present study was designed to investigate whether a systemic cocaine administration affects skin characteristics by elucidating modifications of reactive oxygen species (ROS) production, antioxidant defense and iNOS and XO activity.
  
  
  METHODS
  Two models were used: an in vivo rat model (male Sabra), in which skin specimens were taken 20 days after i.p. cocaine injection (15 mg/kg) and an in vitro model based on HaCaT cells representing human keratinocytes.
  
  
  RESULTS
  Our findings clearly showed that cocaine promoted skin oxidation via the involvement of the enzymes inducible nitric oxide synthase (iNOS) and xanthine oxidase (XO). Cocaine administration significantly increased iNOS expression in rats' skin. It also decreased total scavenging capacity (TSC), as well as reduced glutathione (GSH) and ascorbic acid (AA). HaCaT cells treatment with a cocaine concentration of 2 mM for 24 h (as was chosen by dose-response experiments) markedly enhanced superoxide radicals and peroxides formation. It also decreased TSC and GSH levels. Addition of iNOS and XO inhibitors completely abolished these findings. This study indicates for the first time that systemic cocaine administration affects skin condition, even after a long period of withdrawal.
  
  
  CONCLUSIONS
  Our study therefore, suggests additional metabolic outcomes of cocaine due to its ability to enhance oxidative stress in skin.
authors.affiliation: School of Pharmacy, Institute of Drug Research, The Hebrew University of Jerusalem, Israel.
authors.forename: Meital
authors.initials: M
authors.lastname: Portugal-Cohen
authors.forename: Ran
authors.initials: R
authors.lastname: Numa
authors.forename: Rami
authors.initials: R
authors.lastname: Yaka
authors.forename: Ron
authors.initials: R
authors.lastname: Kohen
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003042:Cocaine / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000166:cytology; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D018384:Oxidative Stress; D010545:Peroxides / Q000737:chemistry; D051381:Rats; D017382:Reactive Oxygen Species; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013481:Superoxides / Q000737:chemistry; D014969:Xanthine Oxidase / Q000378:metabolism*
chemical_list: D018765:Dopamine Uptake Inhibitors; D010545:Peroxides; D017382:Reactive Oxygen Species; D013481:Superoxides; D019001:Nitric Oxide Synthase; D014969:Xanthine Oxidase; D005978:Glutathione; D003042:Cocaine