BACKGROUND: Ultraviolet radiation (UVR) and crude coal tar (CCT) containing PAHs can accelerate the skin-aging process (SAP). However, UVR induces the formation of an important protective factor in SAP (vitamin D). OBJECTIVE: To determine the relation of SAP to selected risks and benefits of combined dermal exposure to UVR and coal tar (PAHs). METHODS: The study group consisted of patients with chronic stable plaque psoriasis and treated by Goeckerman therapy (GT; daily dermal application of UVR and 5% CCT ointment). The levels of urinary 1-hydroxypyrene (1-OHP), oxidative stress (DNA and RNA damage), genotoxic damage (chromosomal aberration in peripheral lymphocytes; ABC), 25-hydroxy-vitamin D [25(OH)D] and the PASI score were evaluated before and after GT. RESULTS: Intensive dermal absorption of PAHs was confirmed by increased levels of 1-OHP (p<0.01). After the therapy, we found an increased level of oxidative stress (p<0.05), an increased level of genotoxic damage (ABC; p<0.001), a high efficiency of the treatment (p<0.001) and an elevated production of 25(OH)D (p<0.01). We also found a relationship between the duration of UVR and the genotoxic damage (p<0.01), vitD (p<0.05) and the PASI score (p<0.05). Furthermore, we found a relationship between oxidative stress and 25(OH)D (p<0.05) and between genotoxic damage and the PASI score (p<0.05). CONCLUSION: Dermal exposure to UVR and coal tar (PAHs) enhances the level of oxidative stress and genotoxic damage and thus contributes to SAP. However, the exposure is very effective as a treatment and elevates the production of 25(OH)D, the protective factor in SAP. According to our results, UVR is probably a more hazardous factor in SAP.
- MeSH
- aplikace kožní MeSH
- biologické markery krev moč MeSH
- časové faktory MeSH
- celotělové ozáření MeSH
- chronická nemoc MeSH
- dehet uhelný aplikace a dávkování škodlivé účinky MeSH
- dospělí MeSH
- keratolytika aplikace a dávkování škodlivé účinky MeSH
- kombinovaná terapie MeSH
- kouření škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- oxidační stres účinky léků účinky záření MeSH
- polycyklické aromatické uhlovodíky aplikace a dávkování škodlivé účinky MeSH
- poškození DNA MeSH
- psoriáza diagnóza metabolismus terapie MeSH
- pyreny moč MeSH
- senioři MeSH
- stabilita RNA účinky léků účinky záření MeSH
- stárnutí kůže účinky léků účinky záření MeSH
- terapie ultrafialovými paprsky škodlivé účinky metody MeSH
- vitamin D analogy a deriváty krev MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The skin is known to be the largest organ in human organism creating interface with outer environment. The skin provides protective barrier against pathogens, physical and chemical insults, and against uncontrolled loss of water. The barrier function was primarily attributed to the stratum corneum (SC) but recent studies confirmed that epidermal tight junctions (TJs) also play important role in maintaining barrier properties of the skin. Independent observations indicate that barrier function and its recovery is impaired in aged skin. However, trans-epidermal water loss (TEWL) values remains rather unchanged in elderly population. UV radiation as major factor of photoageing impairs TJ proteins, but TJs have great self-regenerative potential. Since it may be possible that TJs can compensate TEWL in elderly due to its regenerative and compensatory capabilities, important question remains to be answered: how are TJs regulated during skin ageing? This review provides an insight into TJs functioning as epidermal barrier and summarizes current knowledge about the impact of ageing on the barrier function of the skin and epidermal TJs.
- MeSH
- epidermis metabolismus patologie účinky záření MeSH
- kožní absorpce MeSH
- lidé MeSH
- permeabilita MeSH
- perspiratio insensibilis MeSH
- stárnutí kůže * účinky záření MeSH
- stárnutí metabolismus patologie MeSH
- těsný spoj metabolismus patologie účinky záření MeSH
- ultrafialové záření škodlivé účinky MeSH
- věkové faktory MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
BACKGROUND: Therapeutic options for atopic dermatitis mostly address the symptoms but causal therapies are still missing. Peroxisome proliferator activated receptor (PPAR) agonists exert beneficial effects in patients suffering this disease, whereas the stimulation of PPARα and γ seemed most promising. OBJECTIVES: To elucidate the effects of the PPARα specific agonist WY14643, the PPARγ agonist ciglitazone, and the dual PPARα+γ agonist docosahexaenoic acid (DHA) on the homeostasis and barrier function of filaggrin deficient skin. METHODS: The effects of the PPAR agonists on skin differentiation were evaluated via qPCR, Western blot, histological or immunofluorescence staining. Skin lipid organization was determined by ATR-FTIR and lipid composition was analyzed by HPTLC. Ultimately, the skin barrier function was assessed by skin absorption studies using the radioactively labeled compound testosterone. RESULTS: Significant upregulation of filaggrin after DHA and WY14643 supplementation, but no effect of ciglitazone, on protein and mRNA level was detected. DHA and WY14643, but not ciglitazone, normalized the molar ratio of the main skin barrier lipids to 1:1:1 (free fatty acids:ceramides:cholesterol). Furthermore, DHA and WY14643 supplementation normalized the skin lipid profile in filaggrin deficient skin, but only WY14643 significantly improved the skin barrier function. CONCLUSION: Supplementation particularly with the PPARα agonist WY14643 improved the homeostasis and barrier function of filaggrin deficient skin models by normalization of the free fatty acid profile underlining the potential of PPAR agonists for the treatment of filaggrin-associated skin diseases.
- MeSH
- časové faktory MeSH
- fenotyp MeSH
- fibroblasty účinky léků metabolismus MeSH
- genotyp MeSH
- kožní absorpce účinky léků MeSH
- kultivované buňky MeSH
- kůže účinky léků metabolismus MeSH
- kyseliny dokosahexaenové farmakologie MeSH
- kyseliny mastné neesterifikované metabolismus MeSH
- lidé MeSH
- membránové proteiny genetika metabolismus MeSH
- metabolismus lipidů účinky léků MeSH
- permeabilita MeSH
- PPAR alfa agonisté metabolismus MeSH
- PPAR gama agonisté metabolismus MeSH
- proteinové prekurzory genetika metabolismus MeSH
- proteiny intermediálních filament nedostatek genetika MeSH
- pyrimidiny farmakologie MeSH
- RNA interference MeSH
- signální transdukce účinky léků MeSH
- testosteron metabolismus MeSH
- thiazolidindiony farmakologie MeSH
- transfekce MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Search for new substances with antiproliferative activity towards melanoma cells is important since malignant melanoma is notoriously resistant to conventional chemotherapy. Benzo[c]phenanthridine alkaloids (BAs) are natural products with significant anti-proliferative activities, therefore they are considered as agents promising for cancer therapy. OBJECTIVES: The effects of five BAs (sanguinarine, chelerythrine, chelidonine, sanguilutine, and chelilutine) on human malignant melanoma cell lines were compared. The study focused on BAs effects on DNA, anti-apoptotic and p53 protein levels; and the involvement of p53 in cellular responses to alkaloids treatment. METHODS: Melanoma cell lines, two wild types and two with dysfunctional p53 derived from one of them were used. The mechanism of anti-proliferative and pro-apoptotic effects and the effect on DNA was investigated using MTT assay, flow cytometry, Western blot analysis, fluorescence and electron microscopy. RESULTS: All tested alkaloids exhibit strong anti-proliferative activity. CHL, CHE and SA induced apoptosis, which was probably mediated by decreasing levels of anti-apoptotic proteins (Bcl-xL, Mcl-1, XIAP) and was accompanied by mitochondrial membrane potential decrease as well as caspase-3 and PARP cleavage. Although all alkaloids caused DNA damage, which was demonstrated by induction of H2AX phosphorylation, none of the tested alkaloids stabilised p53 and their toxicity in cells with non-functional p53 was comparable to wild type cells. CONCLUSION: Despite the profound similarity of BAs molecular structures, it is clear that the mechanism of cell death induction is different for each alkaloid. Our results indicate that BAs could be effective in malignant melanoma treatment, including tumours which have lost wild type p53.
- MeSH
- alkaloidy chemie metabolismus farmakologie MeSH
- apoptóza MeSH
- benzofenantridiny farmakologie MeSH
- biologické modely MeSH
- chemické modely MeSH
- chloromethylketony aminokyselin farmakologie MeSH
- DNA metabolismus MeSH
- geny p53 MeSH
- kaspasy metabolismus MeSH
- lidé MeSH
- melanom genetika metabolismus MeSH
- nádorový supresorový protein p53 metabolismus MeSH
- nádory kůže genetika metabolismus MeSH
- poškození DNA MeSH
- proliferace buněk MeSH
- viabilita buněk MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Benign and malignant fibrous histiocytoma present with a considerable difference concerning cellular organization in their vicinity. OBJECTIVE: Normally appearing epithelium covers the malignant form in contrast to hyperplastic epidermis for benign tumors. It is an open question as to whether the tumor-associated fibroblasts are capable to affect phenotypic features of normal keratinocytes, prompting this comparative analysis. METHODS: Fibroblasts were isolated from benign and malignant fibrous histiocytomas, respectively, and also from normal dermis. The resulting cell populations were thoroughly characterized immunocytochemically using a large panel of antibodies. The three fibroblast preparations were cocultured with normal interfollicular keratinocytes. Their phenotype was characterized for distinct properties including differentiation and proliferation. RESULTS: Fibroblasts prepared from both tumor types were phenotypically practically identical with normal dermal fibroblasts. Their activities on keratinocytes were different. Cells prepared from benign fibrous histiocytoma were capable to effect strong expression of keratin 19 and production of a galectin-1-rich extracellular matrix. Fibroblasts isolated from malignant fibrous histiocytoma led to a phenotype very similar to that when keratinocytes were cocultured with normal dermal fibroblasts. CONCLUSION: Fibroblasts prepared from benign fibrous histiocytoma were biologically active on keratinocytes in a particular manner. Our results on fibroblast activity are suggested to be relevant for morphologic differences observed in vivo between normal epidermis and epidermis adjacent to the studied tumor types.
- MeSH
- benigní fibrózní histiocytom metabolismus patologie MeSH
- biologické markery metabolismus MeSH
- epidermis metabolismus patologie MeSH
- fibroblasty metabolismus patologie MeSH
- galektin 1 metabolismus MeSH
- keratin-19 metabolismus MeSH
- keratinocyty metabolismus patologie MeSH
- kokultivační techniky MeSH
- kultivované buňky MeSH
- lidé MeSH
- maligní fibrózní histiocytom metabolismus patologie MeSH
- nádory kůže metabolismus patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- srovnávací studie MeSH
BACKGROUND: Sunlight is a very potent environmental factor in skin pathogenesis and can induce skin cancer. UVB irradiation is known to cause oxidative stress, inflammation and especially DNA damage. Topical application of agents with UV absorbing, antioxidant and anti-inflammatory activities is a successful strategy in the protection of the skin against UV-caused damage. OBJECTIVE: To examine the ability of the phenolic fraction of Lonicera caerulea and Vaccinum myrtillus fruits to moderate UVB-induced damage. METHODS: HaCaT keratinocytes, a well-established in vitro system for investigations on UV radiation induced cell damage, were used to assess the effects of pre- and post-treatment with L. caerulea (LCE) and V. myrtillus (VME) phenolic fractions (5-50 mg/l) on keratinocyte damage induced by a solar simulator (295-315 nm). RESULTS: In this study, a model of UVB-induced damage to HaCaT was established. LCE and VME efficiently reduced the extent of DNA breakage (especially at concentrations of 25 and 10 mg/l) together with caspase-3 and -9 activity and DNA laddering induced by UVB (100 or 200 mJ/cm(2)). LCE and VME significantly decreased RONS generation and partially diminished IL-6 expression. LCE pre-treatment also prevented keratinocytes proliferation. CONCLUSION: The results suggest that the phenolic fraction of L. caerulea and V. myrtillus fruits suppress UVB-caused injury to keratinocytes. These results now need to be demonstrated in vivo.
- MeSH
- apoptóza fyziologie účinky léků MeSH
- buněčné linie MeSH
- fenoly farmakologie chemie MeSH
- flavonoidy farmakologie chemie MeSH
- fototoxická dermatitida prevence a kontrola MeSH
- fragmentace DNA účinky léků MeSH
- interleukin-1beta agonisté metabolismus MeSH
- interleukin-6 agonisté metabolismus MeSH
- jednořetězcové zlomy DNA účinky léků MeSH
- kaspasy metabolismus účinky léků MeSH
- keratinocyty účinky léků účinky záření MeSH
- L-laktátdehydrogenasa analýza MeSH
- lidé MeSH
- Lonicera MeSH
- ovoce chemie MeSH
- polyfenoly MeSH
- přípravky chránící proti slunci farmakologie chemie MeSH
- proliferace buněk účinky léků MeSH
- rostlinné extrakty farmakologie MeSH
- ultrafialové záření škodlivé účinky MeSH
- Vaccinium chemie MeSH
- viabilita buněk fyziologie účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
BACKGROUND: UV radiation from sunlight is a very potent environmental risk factor in the pathogenesis of skin cancer. Exposure to UV light, especially the UVA part, provokes the generation of reactive oxygen species (ROS), which induce oxidative stress in exposed cells. Topical application of antioxidants is a successful strategy for protecting the skin against UV-caused oxidative damage. OBJECTIVE: In this study, silybin (SB) and 2,3-dehydrosilybin (DS) (1-50 micromol/l), flavonolignan components of Silybum marianum, were tested for their ability to moderate UVA-induced damage. METHODS: Human keratinocytes HaCaT were used as an appropriate experimental in vitro model, to monitor the effects of SB and DS on cell viability, proliferation, intracellular ATP and GSH level, ROS generation, membrane lipid peroxidation, caspase-3 activation and DNA damage. RESULTS: Application of the flavonolignans (1-50 micromol/l) led to an increase in cell viability of irradiated (20 J/cm(2)) HaCaT keratinocytes. SB and DS also suppressed intracellular ATP and GSH depletion, ROS production and peroxidation of membrane lipids. UVA-induced caspases-3 activity/activation was suppressed by treatment with SB and DS. Lower concentrations of both compounds (10 micromol/l) significantly reduced cellular DNA single strand break formation. CONCLUSION: Taken together, the results suggest that these flavonolignans suppress UVA-caused oxidative stress and may be useful in the treatment of UVA-induced skin damage.
- MeSH
- antioxidancia farmakologie terapeutické užití terapeutické užití MeSH
- financování organizované MeSH
- kaspasa 3 metabolismus MeSH
- keratinocyty účinky léků účinky záření MeSH
- kůže patologie účinky záření MeSH
- lidé MeSH
- ostropestřec mariánský MeSH
- oxidační stres účinky léků účinky záření účinky záření MeSH
- peroxidace lipidů účinky léků MeSH
- poškození DNA účinky léků MeSH
- proliferace buněk účinky léků MeSH
- radiační poranění prevence a kontrola MeSH
- radioprotektivní látky farmakologie terapeutické užití terapeutické užití MeSH
- reaktivní formy kyslíku metabolismus MeSH
- silymarin farmakologie terapeutické užití MeSH
- transformované buněčné linie MeSH
- ultrafialové záření škodlivé účinky MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
BACKGROUND: UV radiation from sunlight is a potent environmental risk factor in skin cancer pathogenesis. UVA is the major portion of UV light reaching the earth surface ( approximately 95%) and it is reported to lead to benign and malignant tumor formation. UVA-mediated cellular damage occurs primarily through the release of reactive oxygen species (ROS) and it is responsible for inflammation, immunosuppression, photoaging and photocarcinogenesis. OBJECTIVE: The aim of our study was to investigate the potency of silymarin, the polyphenol fraction from the seeds of Silybum marianum, to modulate UVA-induced oxidative damage to human keratinocytes. METHODS: Skin epidermal cell line HaCaT, extensively used for studying the influence of UV radiation, was chosen as an experimental model. Silymarin's effect on UVA-disrupted cell viability, proliferation, mitochondrial function, and intracellular ATP and GSH level was measured. Furthermore, silymarin's potency to reduce UVA-induced ROS generation, membrane lipid peroxidation, caspase-3 activation and DNA damage was monitored. RESULTS: Treatment of irradiated HaCaT (20 J/cm(2)) with silymarin (0.7-34 mg/l; 4h) resulted in concentration-dependent diminution of UVA-caused oxidative stress on all studied parameters. Silymarin application extensively reduced GSH depletion and ROS production as well as lipid peroxidation in irradiated cells. Formation of UVA-induced DNA single strand breaks and caspase-3 activity was also significantly decreased by silymarin. CONCLUSION: The results suggest that silymarin may be beneficial in the treatment of UVA-induced skin oxidative injury and inflammation. However, further studies especially whose using human systems are needed to determine efficacy of silymarin in vivo.
- MeSH
- antioxidancia farmakologie chemie toxicita MeSH
- apoptóza účinky záření účinky záření MeSH
- buněčné dělení účinky léků účinky záření MeSH
- energetický metabolismus účinky léků účinky záření MeSH
- financování organizované MeSH
- keratinocyty cytologie metabolismus účinky léků MeSH
- lidé MeSH
- oxidační stres účinky záření účinky záření MeSH
- poškození DNA účinky léků MeSH
- silymarin farmakologie chemie toxicita MeSH
- transformované buněčné linie MeSH
- ultrafialové záření škodlivé účinky MeSH
- viabilita buněk účinky léků účinky záření MeSH
- Check Tag
- lidé MeSH
