Cocaine induces oxidative damage to skin via xanthine oxidase and nitric oxide synthase

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. Conclusion: Our study therefore, suggests additional metabolic outcomes of cocaine due to its ability to enhance oxidative stress in skin.