Briganti S, Picardo M
Cutaneous Physiopathology Laboratory, San Gallicano Dermatological Institute, 25/A Via S. Gallicano, 00153-Rome, Italy.
J Eur Acad Dermatol Venereol. 2003 Nov;17(6):663-9. doi: 10.1046/j.1468-3083.2003.00751.x.
Due to its interface function between the body and the environment, the skin is chronically exposed to both endogenous and environmental pro-oxidant agents, leading to the harmful generation of reactive oxygen species (ROS). There is compelling evidence that oxidative stress is involved in the damage of cellular constituents, such as DNA, cell membrane lipids or proteins. To protect the skin against the over-load of oxidant species, it contains a well-organised system of both chemical and enzymatic antioxidant which are able to work in a synergistic manner. Skin antioxidant network protects cells against oxidative injury and prevent the production of oxidation products, such as 4-hydroxy-2-nonenal or malonaldehyde, which are able to induce protein damage, apoptosis or release of pro-inflammatory mediators, such as cytokines. When oxidative stress overwhelms the skin antioxidant capacity the subsequent modification of cellular redox apparatus leads to an alteration of cell homeostasis and a generation of degenerative processes. Topical application or oral administration of antioxidants has been recently suggested as preventive therapy for skin photoaging and UV-induced cancer. The recognition that ROS can act as second messengers in the induction of several biological responses, such as the activation of NF-kB or AP-1, the generation of cytokines, the modulation of signalling pathways, etc., has led many researchers to focus on the possible effects of antioxidants in many pathological processes. The recent demonstration that the peroxisome proliferators-activated receptors, whose natural ligands are polyunsaturated fatty acids and theirs oxidation products, have a central role in the induction of some skin diseases, such as psoriasis or acne, has indicated new links between free radicals and skin inflammation. Based on these findings, the review summarises the possible correlations between antioxidant imbalance, lipid oxidative breakage and skin diseases, from both a pathological and therapeutic points of view.
由于皮肤在人体与环境之间起到界面作用,它长期暴露于内源性和环境性促氧化剂中,导致有害的活性氧(ROS)生成。有确凿证据表明氧化应激参与了细胞成分如DNA、细胞膜脂质或蛋白质的损伤。为保护皮肤免受氧化物质的过量侵害,皮肤含有一个组织良好的化学和酶促抗氧化系统,它们能够协同发挥作用。皮肤抗氧化网络保护细胞免受氧化损伤,并防止氧化产物如4-羟基-2-壬烯醛或丙二醛的产生,这些氧化产物能够诱导蛋白质损伤、细胞凋亡或促炎介质如细胞因子的释放。当氧化应激超过皮肤抗氧化能力时,随后细胞氧化还原机制的改变会导致细胞稳态的改变和退行性过程的产生。最近有人提出局部应用或口服抗氧化剂作为皮肤光老化和紫外线诱导癌症的预防性治疗方法。ROS可作为多种生物学反应诱导过程中的第二信使,如激活NF-κB或AP-1、生成细胞因子、调节信号通路等,这一认识促使许多研究人员关注抗氧化剂在许多病理过程中的可能作用。最近的研究表明,过氧化物酶体增殖物激活受体(其天然配体是多不饱和脂肪酸及其氧化产物)在某些皮肤疾病如银屑病或痤疮的诱导中起核心作用,这表明自由基与皮肤炎症之间有了新的联系。基于这些发现,本综述从病理和治疗角度总结了抗氧化剂失衡、脂质氧化损伤与皮肤疾病之间可能的相关性。