Scheuer Cecilie
Dan Med J. 2017 Jun;64(6).
Skin damage induced by UVR is an escalating problem in dermatology, and increasing incidence of skin cancer, especially for non-melanoma skin cancer, has been reported worldwide. UVR from sun exposure and the production of reactive oxygen species (ROS) is known to be a pivotal factor in the aetiology of skin cancer. The pineal hormone melatonin is recognized as the most potent endogenous antioxidant. Melatonin conducts its antioxidant effects acting directly as a radical scavenger and indirectly by up regulation of antioxidant enzymes. It has been proposed, that melatonin may have a protective effect against UVR-induced skin damage. The aim of this thesis was to: - Clarify melatonin's protective effect against UVR-induced skin damage in laboratory and clinical settings trough a systematic review of the literature. - To clinically assess the protective effect of topical treatment with melatonin against natural sun exposure, and determine the optimal concentration. - To clinically evaluate the degree of cognitive dysfunction with full body application of topical melatonin. Study 1: This was a systematic review using the databases Pubmed, EM-BASE and Cinahl. The databases were searched up to January 2013 to identify studies evaluating melatonin's protective effect against UVR-induced erythema in humans, and damage on a cellular level. Twenty studies were included, four human and 16 experimental. The results indicated that melatonin had a protective effect against UVR-induced erythema if applied before exposure, and this effect was probably obtained by melatonin acting directly as an antioxidant, and indirectly by regulating gene expression and inducing a DNA stabilizing effect. As these results were obtained using artificial UVR-sources and without investigating possible side effects, studies using natural sunlight and evaluating possible side effects of topical melatonin administration were warranted. Study 2: This study was a randomized, double-blind, placebo-controlled study. We evaluated the protective effect of three different doses of topical melatonin against erythema induced by natural sun-light. The primary outcome was reduction in erythema, evaluated by chromatography, after sun exposure, when treated with topi-cal melatonin (0.5%, 2.5%, 12.5%) versus placebo and no treatment. A significant difference in erythema formation was found between areas treated with melatonin 12.5% and areas receiving placebo or no treatment. However, this was only seen in participants with an erythema reaction to the sun exposure. Further-more, the treated skin areas were very small and studies assessing any potential adverse effects were necessary. Study 3: This also was a randomized, double-blind, placebo-controlled, cross-over study. We assessed the degree of cognitive dysfunction with full body application of topical melatonin 12.5%. Cognition was evaluated using a neuropsychological test battery consisting of Karolinska sleepiness scale (KSS), finger tapping test (FTT) and continuous reaction time (CRT). The impact on KSS was the primary outcome. We found no significant effect on cognition, however, large inter-individual variation was observed. These results support that melatonin is a safe drug for dermal application. The studies in this thesis may be valuable in the research field of melatonin's protective potential against UVR-induced oxidative skin damage. Increasing incidence of skin cancer is reported worldwide, and experts have suggested that the problem will only increase further, due to depletion of the ozone layer and the aging population. Furthermore, high-risk patient groups are emerging with the widely use of immunosuppressive medicine in various diseases, and this high-risk is in spite of use of protective measures known today. Therefore, development of new and more effective sun protective agents, with other qualities than simple chemical reflection of the UVR, is more important than ever. We have supported the suggestion of melatonin as a sun protective agent, and added the clinical relevant feature, that melatonin also has a protective effect against natural sunlight. Furthermore, we have supported the idea of melatonin being a safe drug for topical treatment, even in previous unknown high dosages. However, before any clinical implementation of melatonin as a sun protective agent can take place, further studies evaluating the long-term effects are warranted.
紫外线辐射（UVR）引起的皮肤损伤是皮肤病学中一个日益严重的问题，据报道，全球皮肤癌的发病率不断上升，尤其是非黑素瘤皮肤癌。已知阳光照射产生的紫外线辐射和活性氧（ROS）的产生是皮肤癌病因中的关键因素。松果体激素褪黑素被认为是最有效的内源性抗氧化剂。褪黑素通过直接作为自由基清除剂和间接上调抗氧化酶来发挥其抗氧化作用。有人提出，褪黑素可能对紫外线辐射引起的皮肤损伤具有保护作用。本论文的目的是：- 通过对文献的系统综述，阐明褪黑素在实验室和临床环境中对紫外线辐射引起的皮肤损伤的保护作用。- 临床评估局部应用褪黑素对自然阳光照射的保护作用，并确定最佳浓度。- 临床评估全身应用局部褪黑素时认知功能障碍的程度。研究1：这是一项使用PubMed、EMBASE和Cinahl数据库的系统综述。对这些数据库进行检索，直至2013年1月，以确定评估褪黑素对人类紫外线辐射引起的红斑以及细胞水平损伤的保护作用的研究。纳入了20项研究，其中4项人体研究和16项实验研究。结果表明，如果在暴露前应用褪黑素，其对紫外线辐射引起的红斑具有保护作用，这种作用可能是通过褪黑素直接作为抗氧化剂以及间接通过调节基因表达和诱导DNA稳定作用而获得的。由于这些结果是使用人工紫外线源获得的，且未调查可能的副作用，因此有必要进行使用自然阳光并评估局部应用褪黑素可能的副作用的研究。研究2：本研究是一项随机、双盲、安慰剂对照研究。我们评估了三种不同剂量的局部褪黑素对自然阳光引起的红斑的保护作用。主要结局是在阳光照射后，用局部褪黑素（0.5%、2.5%、12.5%）与安慰剂及不治疗相比，通过色谱法评估的红斑减少情况。在接受12.5%褪黑素治疗的区域与接受安慰剂或不治疗的区域之间，红斑形成存在显著差异。然而，这仅在对阳光照射有红斑反应的参与者中观察到。此外，治疗的皮肤区域非常小，因此有必要进行评估任何潜在不良反应的研究。研究3：这也是一项随机、双盲、安慰剂对照的交叉研究。我们评估了全身应用12.5%局部褪黑素时认知功能障碍的程度。使用由卡罗林斯卡嗜睡量表（KSS）、手指敲击测试（FTT）和连续反应时间（CRT）组成的神经心理测试组合来评估认知。对KSS的影响是主要结局。我们发现对认知没有显著影响，然而，观察到个体间存在很大差异。这些结果支持褪黑素是一种用于皮肤应用的安全药物。本论文中的研究可能在褪黑素对紫外线辐射引起的氧化性皮肤损伤的保护潜力的研究领域中具有价值。据报道，全球皮肤癌发病率不断上升，专家们认为，由于臭氧层损耗和人口老龄化，这个问题只会进一步加剧。此外，随着免疫抑制药物在各种疾病中的广泛使用，高危患者群体正在出现，而且尽管采用了目前已知的保护措施，这种高风险仍然存在。因此，开发新型、更有效的防晒剂，其具有不同于简单化学反射紫外线辐射的其他特性，比以往任何时候都更加重要。我们支持将褪黑素作为一种防晒剂的建议，并补充了临床相关特征，即褪黑素对自然阳光也具有保护作用。此外，我们支持褪黑素即使在以前未知的高剂量下也是一种用于局部治疗的安全药物的观点。然而，在将褪黑素作为一种防晒剂进行任何临床应用之前，有必要进行进一步评估其长期影响的研究。
