title: Metabolic and redox barriers in the skin exposed to drugs and xenobiotics.
abstract: BACKGROUND
  Growing exposure of human skin to environmental and occupational hazards, to numerous skin care/beauty products, and to topical drugs led to a biomedical concern regarding sustainability of cutaneous chemical defence that is essential for protection against intoxication. Since skin is the largest extra-hepatic drug/xenobiotic metabolising organ where redox-dependent metabolic pathways prevail, in this review, publications on metabolic processes leading to redox imbalance (oxidative stress) and its autocrine/endocrine impact to cutaneous drug/xenobiotic metabolism were scrutinised.
  
  
  METHODS
  Chemical and photo-chemical skin barriers contain metabolic and redox compartments: their protective and homeostatic functions. The review will examine the striking similarity of adaptive responses to exogenous chemical/photo-chemical stressors and endogenous toxins in cutaneous metabolic and redox system; the role(s) of xenobiotics/drugs and phase II enzymes in the endogenous antioxidant defence and maintenance of redox balance; redox regulation of interactions between metabolic and inflammatory responses in skin cells; skin diseases sharing metabolic and redox problems (contact dermatitis, lupus erythematosus, and vitiligo)
  
  
  CONCLUSIONS
  Due to exceptional the redox dependence of cutaneous metabolic pathways and interaction of redox active metabolites/exogenous antioxidants with drug/xenobiotic metabolism, metabolic tests of topical xenobiotics/drugs should be combined with appropriate redox analyses and performed on 3D human skin models.
authors: a Scientific Direction, Centre for Innovative Biotechnological Investigations 'NANOLAB' , Moscow , Russia.
authors: Liudmila
authors: L
authors: Korkina
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008658:Inactivation, Metabolic; D008178:Lupus Erythematosus, Cutaneous / Q000139:chemically induced / Q000175:diagnosis; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D010083:Oxidants, Photochemical / Q000493:pharmacokinetics / Q000633:toxicity; D010084:Oxidation-Reduction / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D014820:Vitiligo / Q000139:chemically induced / Q000175:diagnosis; D015262:Xenobiotics / Q000493:pharmacokinetics* / Q000633:toxicity
chemical_list: D000975:Antioxidants; D051792:Basic Helix-Loop-Helix Proteins; D051267:NF-E2-Related Factor 2; D010083:Oxidants, Photochemical; D018336:Receptors, Aryl Hydrocarbon; D015262:Xenobiotics; C111235:AHR protein, human; C495635:NFE2L2 protein, human
keywords: AhR; GST; Nrf2; contact dermatitis; photo-chemical barrier; redox signalling; skin antioxidants; skin xenobiotic/drug metabolising enzymes; vitiligo