Many studies have demonstrated beneficial health effects of topical antioxidant application; however, the underlying mechanisms are not well understood. To better understand the protective mechanism of oxogenous anti-oxidants, it is important to clarify the physiological distribution, activity and regulation of antioxidants. Also, the generation of ROS by the resident and transient microbial flora and their interaction with cutaneous antioxidants appears to be of relevance for the redox properties of skin. Our studies have demonstrated that alpha-tocopherol is, relative to the respective levels in the epidermis, the major antioxidant in the human SC, that alpha-tocopherol depletion is a very early and sensitive biomarker of environmentally induced oxidation and that a physiological mechanism exists to transport alpha-tocopherol to the skin surface via sebaceous gland secretion. Furthermore, there is conclusive evidence that the introduction of carbonyl groups into human SC keratins is inducible by oxidants and that the levels of protein oxidation increase towards outer SC layers. The demonstration of specific redox gradients within the human SC may contribute to a better understanding of the complex biochemical processes of keratinization and desquamation. Taken together, the presented data suggest that, under conditions of environmentally challenged skin or during prooxidative dermatological treatment, topical and/or systemic application of antioxidants could support physiological mechanisms to maintain or restore a healthy skin barrier. Growing experimental evidence should lead to the development of more powerful pharmaceutical and cosmetic strategies involving antioxidant formulations to prevent UV-induced carcinogenesis and photoaging as well as to modulate desquamatory skin disorders.

The blood‐spinal cord barrier (BSCB), which resides within spinal cord capillaries, is a major impediment to the delivery of drugs used to treat, e.g., traumatic spinal cord injury and amyotrophic lateral sclerosis. These capillaries appear structurally similar to brain capillaries, the site of the blood‐brain barrier (BBB), but we have little information about the molecular basis of BSCB function. Here we demonstrate protein expression (western blots) and transport function (confocal‐based assay) for three ATP‐driven, drug efflux pumps: P‐glycoprotein, multidrug resistance protein 2 (Mrp2) and breast cancer related protein (Bcrp) in capillaries isolated from rat and mouse spinal cords. We show upregulation of transporter function and expression in capillaries exposed to pregnenolone‐16α‐carbonitrile (activates pregnane X receptor), phenobarbital (activates constitutive androstane receptor) and dioxin (activates aryl hydrocarbon receptor). We also show increased P‐glycoprotein expression and transport function in brain capillaries from rats dosed with 5μg/kg TCDD. These results indicate that the BBB and BSCB are remarkably similar with regard to efflux transporter function and regulation.