Эпигаллокатехин egcg лечебные эффекты Кожные болезни Сахарный диабет Ожирение Научные исследования Укрепления здоровья эффекты зеленого чая

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Solar ultraviolet radiation and the skin

The skin is the largest organ of the body and comprises a surface area of approximately 1.5–2.0 m2 which protects the internal organs of the body by acting as an effective barrier against the detrimental effects of environmental and xenobiotic agents. Exposure to solar UV radiation is the key factor in the initiation of several skin disorders, such as wrinkling, scaling, dryness, mottled pigment abnormalities including hypopigmentation and hyperpigmentation, and skin cancer [13, 28, 71].

Although many environmental and genetic factors contribute to the development of various skin diseases, the most important factor is chronic exposure of the skin to solar UV radiation. The solar UV spectrum can be divided into three segments based on the wave lengths of the radiation: short-wave (UVC; 200–290 nm), mid-wave (UVB; 290–320 nm), and long-wave (UVA; 320–400 nm). Each spectrum has a characteristic limit of efficiency in penetrating the epidermal and dermal layers of human and murine skin. A brief detail is as follows:

  1. UVC (200–280 nm) spectrum. UVC radiation is largely absorbed by the atmospheric ozone layer and normally does not reach the surface of the earth. These wavelengths have enormous energy and are mutagenic in nature. UVC radiation can penetrate the skin to a depth of approximately 60–80 micrometer, and can damage DNA molecules.

  2. UVB (280–320 nm) spectrum. UVB radiation constitutes approximately 5% of the total solar UV radiation and is mainly responsible for a variety of skin diseases including nonmelanoma and melanoma skin cancers. UVB radiation can penetrate the skin to a depth of approximately 160–180 micrometer. It can cross the whole epidermis layer and penetrate the dermis compartment of human skin. UVB radiation can induce both direct and indirect adverse biologic effects including induction of oxidative stress, DNA damage, premature aging of the skin [13, 28, 71], and multiple effects on the immune system [51, and reviewed in 64, 74], which together play important roles in the generation and maintenance of UV-induced neoplasms [25, 43, 85]. UVB can act as a tumor initiator [50], tumor promoter [40] and co-carcinogen [17, 104]. Although skin possesses an elaborate defense system consisting of enzymatic and non-enzymatic components to protect the skin from these adverse biological effects, excessive exposure to UV radiation overwhelms and depletes the cutaneous defense system leading to the development of various skin disorders including skin cancer [34, 40, 43, 66]

  3. UVA (320–400 nm) spectrum. UVA comprises the largest spectrum of solar UV radiation (90–95%) and is considered as the “aging ray”. UVA penetrates deeper into the epidermis and dermis of the skin. UVA can penetrate the skin to a depth of approximately 1000 micrometer. It has been shown that extensive UVA exposure can lead to benign tumor formation as well as malignant cancers [5, and reviewed in 92]. The exposure to UVA induces the generation of singlet oxygen and hydroxyl free radicals, which can cause damage to cellular macromolecules, such as proteins, lipids and DNA [16]. In contrast to UVC or UVB, UVA is barely able to excite the DNA molecule directly and produces only a small number of pyrimidine dimers in the skin; therefore, it is assumed that much of the mutagenic and carcinogenic action of UVA radiation is mediated through reactive oxygen species [14, 76]. This, however, is still a matter of debate. It has been suggested that bipyrimidine photoproducts rather than oxidative lesions are the main type of DNA damage involved in the genotoxic effect of solar UVA radiation [18]. UVA is a significant source of oxidative stress in human skin, which causes photoaging in the form of skin sagging rather than wrinkling [53] and can suppress some immune functions [87].

There is ample clinical and experimental evidence to suggest that immune factors contribute to the pathogenesis of solar UV-induced skin cancer in mice and probably in humans as well [88, 101]. Chronically immunosuppressed patients living in regions of intense sun exposure experience an exceptionally high rate of skin cancer [48]. This observation is consistent with the hypothesis that immune surveillance is an important mechanism designed to prevent the generation and maintenance of neoplastic cells. Further, the incidence of skin cancers, especially squamous cell carcinoma, is also increased among organ transplant recipients [12, 20, 72]. The increased frequencies of squamous cell carcinoma, especially in transplant patients, are presumably attributable to a long-term immunosuppressive therapy [15], however nonimmune mechanisms may also play a role [24]. These studies provide evidence in support of the concept that UV-induced immune suppression promotes skin cancer risk.

Polyphenols and skin photoprotection

There has been considerable interest in the use of naturally occurring plant products, including polyphenols, for the prevention of UV-induced skin photodamage primarily including the risk of skin cancer. Polyphenols, specifically dietary, possessing anti-inflammatory, immunomodulatory and anti-oxidant properties are among the most promising group of compounds that can be exploited as ideal chemopreventive agents for a variety of skin disorders in general and skin cancer in particular. Recent advances in our understanding at the cellular and molecular levels of carcinogenesis have led to the development of promising strategies for the prevention of cancer or so called ‘chemoprevention’ strategy. Chemoprevention is a means of cancer control that is based on the use of specific natural or synthetic chemical substances that can suppress, retard or reverse the process of carcinogenesis. In this respect, chemoprevention offers a realistic strategy for controlling the risk of cancers. Furthermore, a chemopreventive approach appears to have practical implications in reducing skin cancer risk because, unlike the carcinogenic environmental factors that are difficult to control, individuals can modify their dietary habits and lifestyle in combination with a careful use of skin care products to prevent the photodamaging effects in the skin. Studies from our laboratory have shown the efficacy of naturally occurring polyphenols, such as green tea polyphenols (GTPs), silymarin from milk thistle and proanthocyanidins from grape seeds (GSPs), against UV radiation-induced inflammation, oxidative stress, DNA damage and suppression of immune responses. Here, we will briefly summarize and discuss the photoprotective potential of some polyphenols, such as polyphenols from green tea and grape seeds as these polyphenols have been the object of extensive in vitro and in vivo studies. The photoprotective role of other plant polyphenols such as silymarin, genistein, and resveratrol also will be discussed. A summary of molecular targets or mechanism of action of these selected polyphenols is given and their sources and molecular structures are described in Table 2 and Figure 1.
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