Thiele J J, Dreher F, Maibach H I, Packer L
Department of Molecular and Cell Biology, University of California, Berkeley, California, USA.
Skin Pharmacol Appl Skin Physiol. 2003 Sep-Oct;16(5):283-90. doi: 10.1159/000072068.
Exposure to ultraviolet radiation or ozone leads to skin damage including oxidation of skin biomolecules, as well as to depletion of constitutive antioxidants. The highly organized stratum corneum forming the main barrier against most xenobiotics is particularly susceptible to such damage and possible barrier perturbation may be the consequence. Whereas ample evidence exists for an increased permeability for different solutes including water after exposure to ultraviolet radiation, such an effect has not yet been reported for ozone. This study reports on the effect of such oxidative stressors using the hairless mouse as the skin model and measuring temperature-controlled transepidermal water loss (TEWL) as an indicator for skin barrier integrity. First, a strong dependency of the TEWL on skin temperature was observed, an effect that was clearly more pronounced than that found in man. Given this temperature dependency in untreated animals, we proceeded to determine the effects of both ultraviolet radiation and ozone on TEWL over a relevant physiological skin temperature range. Solar-simulated ultraviolet radiation (0.75-3 minimal erythemal dose) resulted in a delayed and dose-dependent skin barrier disruption over the entire temperature range investigated. Conversely, daily ozone exposure at 2 ppm for 1 week, however, did not significantly alter TEWL up to 72 h after the last exposure. The results demonstrate a differential response of the epidermis to two environmental stressors associated with oxidative damage; they suggest that chronic ozone exposure at relevant environmental levels does not lead to a detectable skin barrier defect, while solar UV exposure was demonstrated to increase epidermal water loss. Furthermore, experimental evidence clearly suggests that future studies applying TEWL measurements in animal models should be performed under carefully controlled skin temperature conditions.
暴露于紫外线辐射或臭氧会导致皮肤损伤，包括皮肤生物分子的氧化以及内源性抗氧化剂的消耗。构成抵御大多数异生物主要屏障的高度有序的角质层尤其容易受到此类损伤，可能会导致屏障功能紊乱。尽管有充分证据表明暴露于紫外线辐射后不同溶质（包括水）的渗透性会增加，但尚未有关于臭氧产生此类影响的报道。本研究以无毛小鼠为皮肤模型，通过测量温度控制下的经表皮水分流失（TEWL）作为皮肤屏障完整性的指标，报告了此类氧化应激源的影响。首先，观察到TEWL强烈依赖于皮肤温度，这种影响在小鼠中比在人类中更为明显。鉴于未处理动物存在这种温度依赖性，我们进而确定了紫外线辐射和臭氧在相关生理皮肤温度范围内对TEWL的影响。模拟太阳紫外线辐射（0.75 - 3最小红斑剂量）在整个研究温度范围内导致皮肤屏障破坏延迟且呈剂量依赖性。相反，每天暴露于2 ppm臭氧1周，然而，在最后一次暴露后长达72小时内，TEWL没有显著变化。结果表明表皮对两种与氧化损伤相关的环境应激源有不同反应；它们表明在相关环境水平下长期暴露于臭氧不会导致可检测到的皮肤屏障缺陷，而太阳紫外线暴露会导致表皮水分流失增加。此外，实验证据清楚地表明，未来在动物模型中应用TEWL测量的研究应在严格控制的皮肤温度条件下进行。
