The effects of grape seeds polyphenols on SKH-1 mice skin irradiated with multiple doses of UV-B

The study investigated the protective activity of red grape seeds (Vitis vinifera L, Burgund Mare variety) (BM) extracts in vivo on multiple doses of ultraviolet radiation (UV)-B-induced deleterious effects in SKH-1 mice skin. Eighty 8-weeks-old female SKH-1 mice were divided into 8 groups: control, vehicle, UV-B irradiated, vehicle+UV-B irradiated, BM 2.5mg polyphenols (PF)/cm(2)+UV-B irradiated, BM 4 mg PF/cm(2)+UV-B irradiated, UV-B+BM 2.5mg PF/cm(2), UV-B+BM 4 mg PF/cm(2). The extract was applied topically before or after each UV-B exposure (240 mJ/cm(2)), for 10 days consecutively. The antioxidant activity of BM extract is higher than gallic acid (k(BM)=0.017, k(gallic acid)=0.013). Multiple doses of UV-B generated the formation of cyclobutane pyrimidine dimers (CPDs) and sunburn cells, increased glutathione peroxidase (GPx) and catalase (CAT) activities respectively glutathione (GSH) and IL-1β levels in skin. In group treated with 2.5mg PF/cm(2) before UV-B irradiation BM extract inhibited UV-B-induced sunburn cells, restored the superoxide dismutase (MnSOD) activity, increased insignificantly CAT and GPx activities and reduced IL-1β level. The BM 4.0 mg PF/cm(2) treatment decreased GSH level and reduced the percentage of CPDs positive cells in skin. Both doses of BM extract administered after UV-B irradiation increased the MnSOD and GPx activities and reduced the formation of sunburn cells in skin. Our results suggest that BM extract might be a potential chemo-preventive candidate in reducing the oxidative stress and apoptosis induced by multiple doses of UV-B in skin.     

Ultraviolet B light stimulates interleukin-20 expression by human epithelial keratinocytes

The proinflammatory cytokine interleukin-20 (IL-20) may exert the majority of its activity in the skin. We examined the effect of various treatments including several forms of phototherapy on IL-20 expression using cultured normal human epithelial keratinocytes (NHEK). Broadband UVB light, recombinant (r) IL-1 and rIL-8 increased, while hydrocortisone reduced, NHEK supernatant IL-20 levels. Elevation of NHEK IL-20 mRNA and maximal supernatant IL-20 levels occurred with a UVB light dose (40 mJ cm(-2)) that reduced cell viability by approximately 50%. While this UVB light dose also elevated supernatant IL-1 alpha and IL-8 levels, antibody neutralization studies indicated that neither of these cytokines was directly responsible for this increase in IL-20 expression. However, the elevation in IL-20 levels was fully inhibited by the p38 mitogen-activated protein kinase (MAPK) inhibitor SB-203580, suggesting involvement of this stress signaling pathway in this UVB light response. Photodynamic therapy (PDT) with the photosensitizer lemuteporfin, UVA light, cisplatin, lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha) or recombinant interferon-gamma (rIFN-gamma) either had little effect or decreased NHEK supernatant IL-20 levels. Reduced IL-20 levels paralleled the cytotoxic actions of PDT, UVA light or cisplatin and the antiproliferative effect of rIFN-gamma. Neither rIL-20 supplementation nor anti-IL-20 antibody treatments affected cell viability indicating that soluble IL-20 did not affect the short-term survival of UVB light-irradiated NHEK. Stimulation of IL-20 expression in keratinocytes by UVB light suggests that this cytokine might participate in skin responses to this ever-present environmental factor and potentially has a role in UV light-associated dermatoses.     

UV-induced unscheduled DNA synthesis in human skin: dose response, correlation with erythema, time course and split dose exposure in vivo

Unscheduled DNA synthesis (UDS) has been shown to be saturated above a threshold dose of UV-C in human fibroblasts in vitro. We have investigated by autoradiography whether a similar saturation occurs in human skin in vivo with UV-B and whether this phenomenon correlates with the erythemal response. In addition, we determined the time course of UDS at 24 h after exposure and the effect of dual exposures separated by 24 h. The dose-response curve was established by exposure to 1/16, 1/8, 1/4, 1/2, 1, 2, 3, 4 and 6 MEDs UV-B. For the time-course study, areas exposed to 1/2 and 2 MEDs were biopsied after 1, 3, 6, 12 and 24 h. Autoradiography was performed in vitro. The dose-response curve showed a significant increase in UDS from 1/16 to 1 minimal erythema dose (MED), whereas no significant difference was observed between 1 MED and the higher UV-B doses tested. The 24 h time sequence revealed a gradual decrease in UDS activity. The 1/2 MED curve declined more rapidly and reached the zero-level between 12 h and 24 h, whereas about 50% of the initial UDS value was still retained 24 h after 2 MEDs. The dual-dose study revealed that a second hit of fractions of the MED resulted in lower levels of UDS than induced by these fractions alone in previously untreated areas. UDS increases with the erythemal dose between 1/16 and 1 MED. It reaches a plateau after 1 MED and cannot be increased by doses up to 6 MEDs, suggesting a saturation of excision repair in vivo. Time course studies support such a saturation phenomenon. The failure to increase significantly UDS by a second irradiation 24 h after the first exposure needs further clarification. Since persistence of DNA lesions may lead to an accumulation after repeated exposures, additional mechanisms other than excision repair may protect human skin by error-free removal of possibly mutagenic sites. Photoreactivation may be important in this respect.     

UV erythema reducing capacity of mizolastine compared to acetylsalicylic acid or both combined in comparison to indomethacin.

UV light exerts hazardous effects such as induction of skin cancer and premature skin aging. In this study we evaluated an assumptive anti-inflammatory effect of the nonsedative histamine H1-receptor antagonist, mizolastine, on UV-induced acute sunburn reaction. Therefore, a clinical, randomized, double-blind, four-arm, crossover study was conducted in healthy young female volunteers (skin type II) comparing the UV sensitivity under mizolastine, acetyl-salicylic acid (ASA), indomethacin or a mizolastine/ASA combination. Moreover, HaCaT keratinocytes were incubated with mizolastine under various UV treatment modalities in vitro to study its effect on the release of inflammatory cytokines, i.e. interleukin (IL)-1 alpha, IL-6 and tumor necrosis factor alpha (TNF-alpha). All three drugs were effective in suppressing the UVB-, UVA- and combined UVA/UVB-erythema. However, the strongest effects were observed using the combined treatment with both 250 mg ASA and 10 mg mizolastine. An inhibitory effect in vitro of 10 nM mizolastine upon UV-induced cytokine release from HaCaT keratinocytes was observed for IL-1 alpha at 24 h after 10 J/cm2 UVA1, for IL-6 at 48 h after 10 J/cm2 UVA1 and 30 mJ/cm2 UVB, and also for TNF-alpha at 4 h after 10 J/cm2 UVA, 10 J/cm2 UVA1 and 30 mJ/cm2 UVB, respectively. The combination of mizolastine and ASA can be strongly recommended as a protective measure against UV erythema development with a lower unwanted side effect profile than that of the hitherto treatment modality, i.e. indomethacin.     

Adaptation of the human skin by chronic solar-simulating UV irradiation prevents ultraviolet-B irradiation-induced rise in serum C-reactive protein levels

Exposure of the skin to UV radiation induces local inflammation. We hypothesized that inflammation induced by erythemal UV-B irradiation could elevate levels of serum C-reactive protein (CRP) and that suberythemal repeating doses of solar-simulating UV radiation (SSR) would produce photoadaptation to such inflammation. Separation-free high-sensitivity assays of CRP show an increase by 42% (P = 0.046) in CRP concentrations in healthy human subjects 24 h after a 3 minimal erythemal dose (MED) dose of UV-B delivered onto a 100 cm2 skin area. Preceding daily suberythemal doses of whole-body SSR for 10 or 30 consecutive days completely prevented the CRP increase. UV-B-induced skin erythema was partially attenuated by 30 preceding days of SSR only (P = 0.00066). After 10 daily SSR doses, the mean baseline CRP concentrations (0.24 +/- 0.21 mg/L) declined by 35% (P = 0.018). Using high-sensitivity analysis of serum CRP as the endpoint marker for cutaneous inflammation, we show that acute exposure of even a relatively small skin area to erythemal UV-B induces skin inflammation detectable also at the systemic level and that photoadaptation by preceding repeating suberythemal doses of SSR reduces signs of inflammation. Our data complement the view given by previous studies in that local photoadaptation also has systemic manifestations.     

Synergy between adiponectin and interleukin-1β on the expression of interleukin-6, interleukin-8, and cyclooxygenase-2 in fibroblast-like synoviocytes

To determine whether adiponectin may have synergistic effects in combination with the proinflammatory cytokine interleukin (IL)-1β regarding the production of proinflammatory mediators during arthritic joint inflammation, synovial cells from rheumatoid arthritis (RA) patients were treated with adiponectin, IL-1β, and their combination for 24 h. Culture supernatant was collected and analyzed by enzyme-linked immunosorbent assay for levels of IL-6, IL-8, prostaglandin E(2) (PGE(2)), vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMPs). Adiponectin-mediated intracellular signaling pathways were investigated to elucidate the molecular mechanisms underlying their synergy. The association of proinflammatory mediators with adiponectin was investigated in the synovial fluid of arthritis patients. Adiponectin functioned synergistically with IL-1β to activate IL-6, IL-8, and PGE2 expression in RA fibroblast-like synoviocytes; Levels of VEGF, MMP-1, and MMP-13 were not synergistically stimulated. Adiponectin and IL-1β each increased the expression of both adiponectin receptor 1 and IL-1 receptor 1. However, adiponectin and IL-1β did not synergistically support the degradation of IκB-α or the nuclear translocation of NF-κB. Synergistically increased gene expression was significantly inhibited by MG132, an NF-κB inhibitor. Supporting the in vitro results, IL-6 and IL-8 levels were positively associated with adiponectin in synovial joint fluid from patients with RA, but not osteoarthritis (OA). In conclusion, adiponectin and IL-1β may synergistically stimulate the production of proinflammatory mediators through unknown signaling pathways during arthritic joint inflammation. Adiponectin may be more important to the pathogenesis of RA than previously thought.     

p53 induction in normal human skin in vitro following exposure to solar simulated UV and UV-B irradiation.

Exposure of normal human breast skin ex vivo to physiological levels of UV-B and solar simulated UV results in a UV dose- and time-dependent increase in epidermal p53, as determined by PAGE analysis. Peak p53 levels are detected 12 to 24 h post irradiation with UV-B (470-1410 mJ cm-2) and solar simulated UV (5-12 minimal erythema dose (MED) equivalents). Irradiation with an FS20 UV-B lamp, contaminated with UV-A and UV-C (74-1111 mJ cm-2), also induces peak levels after 12 h incubation at 37 degrees C but these levels persist to 36 h post UV irradiation. In all cases p53 levels start to return to normal by 48 h culture. A significant positive correlation is demonstrated between UV-B dose (47-1645 mJ cm-2) and p53 level (p < 0.01, R > 0.977) in explants cultured for 24 h at 37 degrees C post irradiation. The FS20 induces a 'UV-B' dose-dependent increase in p53 to a maximum from 370 to 1111 mJ cm-2. Similarly, solar simulated UV induces a plateau of peak p53 induction between 5 and 15 MED equivalents. Immunohistochemical analysis using microwave retrieval on 5 microns sections shows the same pattern of p53 staining with UV-B and solar UV insult, but proves unreliable as a method of quantification. These results suggest that the skin explant model may be a useful tool in the evaluation of UV-induced epidermal cell damage, providing a valuable alternative to in vivo studies.     

Effect of bosentan on the production of proinflammatory cytokines in a rat model of emphysema

Endothelin (ET) receptor antagonists have been developed to produce a reduction of ET related effects in various diseases, as well as in animal models of airway inflammation. We aimed to investigate the anti-inflammatory potential of bosentan on a rat model of emphysema. Thirty Wistar male rats were classified as control group (group 1), intratracheally (i.t.) instilled with saline, treated with vehicle solution; elastase group (group 2), i.t. instilled with porcine pancreatic elastase (PPE), treated with vehicle solution; and PPE+bosentan group (group 3), i.t. instilled with PPE, treated with bosentan. The levels of TNF-alpha, IL-1beta, IL-6, and IL-8 in bronchoalveolar lavage fluid (BALF) and lung tissue, cell counts in BALF, and histologic analysis of all groups were evaluated. Neutrophile granulocytes (NG) and alveolar macrophages (AM) were increased more in group 2 than in group 1 (P<0.001, P=0.04, respectively). Compared with group 2, neutrophil granulocyte (NG) and alveolar macrophages (AM) counts were decreased in group 3 (P<0.001). Histological examination confirmed a diffuse neutrophilic inflammation and irregular alveolar air space enlargement in group 2. Treatment with bosentan partially reduced the enlarged lung volumes. Compared with group 1, the BALF levels of TNF-alpha and IL-6, and the lung tissue levels of IL-1beta, IL-6, and IL-8 were increased in group 2 (P=0.028, P=0.005, P=0.001, P=0.019, P<0.001, respectively). The TNF-alpha and IL-8 levels of BALF (P=0.007, P=0.001, respectively), and the TNF-alpha, IL-1beta, IL-6, and the IL-8 levels of lung tissue (P=0.031, P=0.017, P=0.007, P<0.001) were decreased in group 3 compared to group 2. In conclusion, bosentan decreased the inflammatory response by reducing numbers of inflammatory cells and proinflammatory cytokines.     

Transmission of UV-radiation through human epidermal layers as a factor influencing the minimal erythema dose

Abstract— The extent to which transmission of human Caucasian epidermis and stratum corneum influences the Minimal Erythema Dose (MED) was examined for UV-B and UV-C.
Transmission correlated well with variations in MED for UV-B and UV-C that exist between individuals, as measured on the skin of the lower back and anterior upper leg.
Regional differences of the MED that occur within the same individual between different parts of the body, were related less well to differences in transmission. For UV-B, the difference in transmission of stratum corneum and epidermis between upper leg and lower back was on the average too small to completely account for the difference in MED UV-B. Other parameters, therefore, have to be involved in determining such regional variations in MED UV-B. For UV-C, on average, the difference in transmission of stratum corneum was smaller and of epidermis larger than the difference in MED UV-C between upper leg and lower back, though the deviations were not significant.
A series of UV-B irradiations of the lower back resulted in an increase in MED UV-B and MED UV-C, which was paralleled by a decrease in transmission of stratum corneum and epidermis. The average decrease in UV-B transmission of stratum corneum was too small and that of epidermis somewhat too large to account for the average increase in MED UV-B. The average decrease in UV-C transmission of stratum corneum was about as large as the average increase in MED UV-C. Consequences of these observations for the location of the primary reactions leading to erythema are discussed.
The relationship between log MED UV-C and log MED UV-B was confirmed to be approximately linear.     

Celastrol inhibits production of nitric oxide and proinflammatory cytokines through MAPK signal transduction and NF-kappaB in LPS-stimulated BV-2 microglial cells

Excessive production of nitric oxide (NO) and proinflammatory cytokines from activated microglia play an important role in human neurodegenerative disorders. Here, we investigated whether celastrol, which has been used as a potent anti-inflammatory and anti-oxidative agent in Chinese medicine, attenuates excessive production of NO and proinflammatory cytokines such as TNF-alpha and IL-1betal in LPS-stimulated BV-2 cells, a mouse microglial cell line. We report here that the LPS-elicited excessive production of NO, TNF-alpha, and IL-1beta in BV-2 cells was largely inhibited in the presence of celastrol, and the attenuation of inducible iNOS and these cytokines resulted from the reduced expression of mRNAs of iNOS and these cytokines, respectively. The molecular mechanisms that underlie celastrol-mediated attenuation were the inhibition of LPS-induced phosphorylation of MAPK/ERK1/2 and the DNA binding activity of NF-kappaB in BV-2 cells. The results indicate that celastrol effectively attenuated NO and proinflammatory cytokine production via the inhibition of ERK1/2 phosphorylation and NF-kappaB activation in LPS-activated microglia. Thus, celastrol may be an effective therapeutic candidate for use in the treatment of neurodegenerative human brain disorders.     

Effects of UVR and UVR-induced cytokines on production of extracellular matrix proteins and proteases by dermal fibroblasts cultured in collagen gels%

Synthesis of extracellular matrix (ECM) proteins and their degradation by matrix metalloproteinases (MMP) are part of the dermal remodeling resulting from chronic exposure of skin to ultraviolet radiation (UVR). We have compared two alternative mechanisms for these responses, namely, a direct mechanism in which UV-B or UV-A is absorbed by fibroblasts and an indirect mechanism in which cytokines, produced in skin in response to UVR, stimulate production of the ECM proteins and MMP. These studies were carried out on human dermal fibroblasts grown in contracted, free-floating 9 day old collagen gels as a dermal equivalent. Synthesis of tropoelastin, collagen, fibrillin, MMP-1, -2, -3 and -9 and tissue inhibitors of metalloproteinases (TIMP)-1 and -2 were measured. Tropoelastin, collagen and fibrillin levels were stable between days 4 and 10, and MMP and TIMP decreased by day 10. Neither UV-B (2.5-50 mJ/cm2) nor UV-A (2-12 J/cm2) altered synthesis of ECM proteins, but UV-A increased MMP-1 and -3 production. Tropoelastin synthesis increased in response to transforming growth factor-beta1 (5 ng/mL) treatment. Both interleukin-1beta and tumor necrosis factor-alpha (10 ng/mL) decreased fibrillin messenger RNA levels but increased MMP-1, -3 and -9 synthesis markedly. Collagen synthesis was not modulated by UV-B, UV-A or cytokine treatment. These results indicate that certain cytokines may have greater effects on production of ECM proteins and MMP than absorption of UV-B and UV-A by fibroblasts grown in dermal equivalents and suggest that the former pathway may play a role in the dermal remodeling in photoaged skin.     

A prospective, randomized, placebo-controlled, double-blinded, and split-face clinical study on LED phototherapy for skin rejuvenation: clinical, profilometric, histologic, ultrastructural, and biochemical evaluations and comparison of three different treatment settings

Light-emitting diodes (LEDs) are considered to be effective in skin rejuvenation. We investigated the clinical efficacy of LED phototherapy for skin rejuvenation through the comparison with three different treatment parameters and a control, and also examined the LED-induced histological, ultrastructural, and biochemical changes. Seventy-six patients with facial wrinkles were treated with quasimonochromatic LED devices on the right half of their faces. All subjects were randomly divided into four groups treated with either 830nm alone, 633nm alone, a combination of 830 and 633nm, or a sham treatment light, twice a week for four weeks. Serial photography, profilometry, and objective measurements of the skin elasticity and melanin were performed during the treatment period with a three-month follow-up period. The subject's and investigator's assessments were double-blinded. Skin specimens were evaluated for the histologic and ultrastructural changes, alteration in the status of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), and the changes in the mRNA levels of IL-1ss, TNF-alpha, ICAM-1, IL-6 and connexin 43 (Cx43), by utilizing specific stains, TEM, immunohistochemistry, and real-time RT-PCR, respectively. In the results, objectively measured data showed significant reductions of wrinkles (maximum: 36%) and increases of skin elasticity (maximum: 19%) compared to baseline on the treated face in the three treatment groups. Histologically, a marked increase in the amount of collagen and elastic fibers in all treatment groups was observed. Ultrastructural examination demonstrated highly activated fibroblasts, surrounded by abundant elastic and collagen fibers. Immunohistochemistry showed an increase of TIMP-1 and 2. RT-PCR results showed the mRNA levels of IL-1ss, TNF-alpha, ICAM-1, and Cx43 increased after LED phototherapy whereas that of IL-6 decreased. This therapy was well-tolerated by all patients with no adverse effects. We concluded that 830 and 633nm LED phototherapy is an effective approach for skin rejuvenation.     

Effects of UV Radiation and Diet on Polyunsaturated Fatty Acids in the Skin,Ocular Tissue and Dorsal Muscle of Atlantic Salmon (Salmo salar) Held in Outdoor Rearing Tanks

The effect of UV radiation (UVR) on juvenile Atlantic salmon (Salmo salar) was assessed by measuring the fatty acid (FA) profiles of muscle, dorsal and ventral skin, and ocular tissues following 4-month long exposures to four different UVR treatments in outdoor rearing tanks. Fish were fed two different diets (Anchovy- and Herring-oil based) that differed in polyunsaturated fatty acid (PUFA) concentrations. Anchovy-fed salmon had higher concentrations of ALA (alpha-linoleic acid; 18:3n-3), EPA (eicosapentaenoic acid; 20:5n-3) and DPA (docosapentaenoic acid, 22:5n-3) in their muscle tissues than fish fed the Herring feed. Fish subjected to enhanced UVB levels had higher concentrations of LIN (linolenic acid, 18:2n-6) and ALA, total omega-6 FA and SAFA (saturated fatty acids) in their tissues compared with fish in reduced UV treatments. Concentrations of ALA, LIN, GLA (gamma-linolenic acid; 18:3n-6), EPA, PUFA and total FA were higher in ventral skin of fish exposed to enhanced UVB compared with fish in reduced UV treatments. Salmon exposed to reduced UV weighed more per-unit-length than fish exposed to ambient sunlight. The FA profiles suggest that fish exposed to UV radiation were more quiescent than fish in the reduced UV treatments resulting in a buildup of catabolic substrates.     

Skin Erythema,Pigmentation and Hydration Kinetics after Ultraviolet Radiation‐induced Photodamage in Southern Chinese Women

Although there have been some studies about changes of skin erythema and pigmentation following ultraviolet radiation in other races, the relevant data in Chinese have never been achieved. Thus, we evaluated the long‐time course of skin erythema, pigmentation and hydration changes after different doses of solar‐simulated ultraviolet (SSUV) irradiation in 26 Chinese women for 168 days. The erythema index increased abruptly and peaked during 3 days of SSUV exposure, then slowly returned to the baseline level starting at day 7 and completely recovered during 168‐day course of this study only in one minimal erythema doses (MED) SSUV irradiation. The melanin index started to slowly increase at day 3 of SSUV exposure, peaking at day 14 and gradually returned to the baseline level thereafter, but did not return to the baseline level during 168‐day course in all doses. Skin hydration slowly declined at day 3 of exposure, hitting the lowest point at day 7, then slowly recovered starting at day 14 and completely returned to the baseline level at day 28 only in 1.5MED. These results will serve as baseline data on Chinese skin and provide useful references for the treatment of serious skin photodamage in Chinese.     

Objective measurement of minimal erythema and melanogenic doses using natural and solar-simulated light

Very little information exists on the amount of natural and artificial UV light required to cause sunburn and tanning in individuals with very pale skin who are at the greatest risk of developing skin cancer. We have investigated minimal erythema dose (MED) and minimal melanogenic dose (MMD) in a group of 31 volunteers with Fitzpatrick skin types I and II using an Oriel 1000 W xenon arc solar simulator and natural sunlight in Sydney, Australia. We measured the erythemal and melanogenic responses using conventional visual scoring, a chromameter and an erythema meter. We found that the average MED measured visually using the artificial UV source was 68.7 +/- 3.3 mJ/cm2 (3.4 +/- 0.2 standard erythema doses [SED]), which was significantly different from the MED of sunlight, which was 93.6 +/- 5.6 mJ/cm2 (P < 0.001) (11.7 +/- 0.7 SED). We also found significant correlations between the solar-simulated MED values, the melanin index (erythema meter) and the L* function (chromameter). The average MMD (obtained in 16 volunteers only) using solar-simulated light was 85.6 +/- 4.9 mJ/cm2, which was significantly less than that measured with natural sunlight (118.3 +/- 8.6 mJ/cm2; P < 0.05). We mathematically modeled the data for both the chromameter and the erythema meter to see if we were able to obtain a more objective measure of MED and differentiation between skin types. Using this model, we were able to detect erythemal responses using the erythema index function of the erythema meter and the a* function of the chromameter at lower UV doses than either the standard visual or COLIPA methods.     

Ultraviolet-B radiation effects on antioxidant status and survival in the zebrafish, Brachydanio rerio

Direct impact of ambient (1.95 W/m2) and subambient doses of UV-B radiation on muscle/skin tissue antioxidant status was assessed in mature zebrafish (Brachydanio rerio). The influence of these doses on hatching success and survival in earlier life stages was also examined. Subambient doses of UV-B radiation in the presence (1.28 W/m2) and absence (1.72 W/m2) of a cellulose acetate filter significantly depressed muscle/skin total glutathione (TGSH) levels compared with controls (0.15 W/m2) and low (0.19 W/m2) UV-B-treated fish after 6 and 12 h cumulative exposure. Ambient UV-B exposure significantly decreased muscle/skin glutathione peroxidase (GPx) activity after a 6 h exposure; activities of glutathione reductase (GR) were unchanged over this exposure period. Superoxide dismutase (SOD) and catalase activities peaked after 6 and 12 h cumulative exposure, respectively, but fell back to control levels by the end of the exposure period. The changes in tissue antioxidant status suggested UV-B-mediated increases in cytosolic superoxide anion radicals (O2-) and hydrogen peroxide (H2O2). This apparent UV-B-mediated increase in oxidative stress is further supported by a significant increase in muscle/skin thiobarbituric acid reactive substances (TBARS). Hatching success of newly fertilized eggs continuously exposed to ambient UV-B was only 2% of the control value. Even at 30 and 50% of ambient UV-B, hatching success was only 80 and 20%, respectively, of the control. Newly hatched larvae exposed to an ambient dose of UV-B, experienced 100% mortality after a 12 h cumulative exposure period. This study supports a major impact of UV-B on both the mature and embryonic zebrafish.     

Green tea phenol extracts reduce UVB-induced DNA damage in human cells via interleukin-12

Green tea chemoprevention has been a focus of recent research, as a polyphenolic fraction from green tea (GTP) has been suggested to prevent UV radiation-induced skin cancer. Recently, it was demonstrated that GTP reduced the risk for skin cancer in a murine photocarcinogenesis model. This was accompanied by a reduction in UV-induced DNA damage. These effects appeared to be mediated via interleukin (IL)-12, which was previously shown to induce DNA repair. Therefore, we studied whether GTP induction of IL-12 and DNA repair could also be observed in human cells. KB cells and normal human keratinocytes were exposed to GTP 5 h before and after UVB. UVB-induced apoptosis was reduced in UVB-exposed cells treated with GTP. GTP induced the secretion of IL-12 in keratinocytes. The reduction in UV-induced cell death by GTP was almost completely reversed upon addition of an anti-IL-12-antibody, indicating that the reduction of UV-induced cell death by GTP is mediated via IL-12. The ability of IL-12 to reduce DNA damage and sunburn cells was confirmed in "human living skin equivalent" models. Hence the previously reported UV-protective effects of GTP appear to be mediated in human cells via IL-12, most likely through induction of DNA repair.     

Determination of the minimal erythema dose and colorimetric measurements as indicators of skin sensitivity to UV-B radiation

There is a strong relation between chronic UV-B-induced sunburns and the development of skin cancer. Therefore, it is important to obtain a method that can be reproduced easily to detect individuals with similar skin color but different sensitiveness to sun exposure. The study evaluated 193 healthy volunteers (68% women; the average age was 38 years). They were divided into six groups of at least 30 subjects, according to skin type. The minimal erythema dose (MED) was assessed in two non-sun-exposed areas (thorax-infra-axillary area and on the buttocks), using a UV-B source (0.5 mW/cm2), with openings of 1 cm2, in increasing doses. The same areas were evaluated with a Minolta CR 300 Chromameter (L*a*b* system). The MED values ranged from 13 to 156 mJ/cm2; the coordinate L* (brightness) ranged from 75.96 to 30.15. The correlation between the MED and the brightness was negative in both areas (Pearson's correlation r = -0.91, P < 0.05). Color measurements, especially brightness, can be used to quickly assess skin sensibility. Considering the MED, there is a substantial overlapping of adjacent phototypes, but they could be separated into two groups: more sensitive individuals (Types I, II, III and IV) and less sensitive ones (Types V and VI).