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2.
Toxicol Appl Pharmacol ; 399: 115040, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32422325

RESUMO

Radiation-induced dermatitis is a common occurrence in cancer patients undergoing radiation therapy (RT) and is caused when ionizing radiation (IR) induces DNA strand breaks in skin cells. The wide use of RT in cancer treatments makes it important to minimize RT-induced toxicities including radiodermatitis. This study sought to determine if the circadian clock plays a protective role in minimizing radiodermatitis. We treated mice in control (Day Shift), environmentally-disrupted (Rotating Shift) and genetically-disrupted (Per 1/2-/-) circadian conditions with 6 Gy of IR to the whole body. There was a significantly increased number of radiodermatitis spots on mice with circadian clock disruption compared to control mice. Additionally, circadian clock disrupted mice exhibited reduced protein levels of Bmal1, a phenomenon that sensitized circadian synchronized keratinocytes to IR-induced DNA damage. Furthermore, the skin phenotype results corresponded with significantly reduced body weights and increased genomic DNA damage in blood cells of mice with clock disruption compared to control mice. These findings suggest that the circadian clock plays a protective role in IR-induced DNA damage and skin toxicity, possibly through BMAL1-dependent mechanisms, and potentially impacts RT-associated radiodermatitis in cancer patients.


Assuntos
Relógios Circadianos/genética , Ritmo Circadiano/genética , Radiodermatite/genética , Fatores de Transcrição ARNTL/genética , Animais , Dano ao DNA/genética , Dano ao DNA/efeitos da radiação , Feminino , Queratinócitos/efeitos da radiação , Camundongos , Camundongos Pelados , Neoplasias/genética , Neoplasias/radioterapia
3.
PLoS One ; 15(4): e0232009, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32353018

RESUMO

Non-melanoma skin cancer (NMSC) has a high and increasing incidence all over the world. Solar radiation is the main aetiology for humans. Although most research into photocarcinogenesis uses UVB as a source of radiation, UVA is also carcinogenic in long term. Pomegranate (PGE) and cocoa (CE) extracts have been used for medicinal purposes for time immemorial. Recently, it has been claimed that some of their properties may be an effective preventative measure against photocarcinogenesis and photoaging, but to date in vivo models have not been tested using RUVA, the objective of the present work. A lower incidence of lesions was observed in SKH-1 mice treated with PGE (p<0.001), and lower incidence of invasive squamous carcinoma in both treatment groups (p<0.001 for PGE and p<0.05 for CE); the PGE group also showed a lower level of cell proliferation than the control group (p<0.001). Significantly greater p53 alteration was observed in the control group than the treatment groups (p<0.001 for PGE and p = 0.05 for CE). No significant differences were found in relation to TIMP-1 and MMP-9. Taken together, the results suggest that oral feeding of PGE and CE to SKH-1 mice affords substantial protection against the adverse effects of RUVA, especially PGE.


Assuntos
Quimioprevenção/métodos , Neoplasias Induzidas por Radiação/prevenção & controle , Extratos Vegetais/farmacologia , Animais , Anticarcinógenos/farmacologia , Cacau/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Pelados , Neoplasias Induzidas por Radiação/patologia , Romã (Fruta)/efeitos dos fármacos , Pele/patologia , Neoplasias Cutâneas/patologia , Raios Ultravioleta/efeitos adversos
5.
Chem Biol Interact ; 321: 109031, 2020 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-32142722

RESUMO

Reactive oxygen species (ROS) is mainly produced as a by-product from electron transport chain (ETC) of mitochondria and effectively eliminated by cellular antioxidants. However, 2-chloroethyl ethyl sulfide (CEES) exposure to keratinocytes declined antioxidant capacity and increased accumulation of ROS triggered alteration of mitochondrial activity and apoptosis is lacking. Our findings demonstrated that the electron leakage from the impaired ETC, leading to the accumulation of ROS was gradually elevating with increasing concentration of CEES exposure, which decline the activity of superoxide dismutase (SOD), manganese SOD (MnSOD) and copper-zinc SOD (Cu-ZnSOD) in keratinocytes. Further, excess accumulation of ROS, decreased the mitochondrial membrane potential (ΔΨm) and increased the mitochondrial mass with increasing dose of CEES. CEES exposure provoked the decrease in expression of transcription factor A mitochondrial (TFAM), augmented mitochondrial DNA (mtDNA) damage and altered the mtDNA-encoded oxidative phosphorylation (OXPHOS) subunits. Moreover, fragmented mtDNA translocated into cytosol, where it activated cGAS-STING and interferon regulatory factor3 (IRF3), coinciding with the increased expression of inflammatory mediators and alteration of cell-to-cell communication markers. Pre-treatment of N-acetyl-l-cysteine (NAC) or L-Nω-nitroarginine methyl ester (NAME), hydralazine hydrochloride (Hyd·HCl) or ERK1/2 or phosphoinositide3-kinase (PI3-K)/Akt inhibitors in keratinocyte cells significantly restored the CEES effect. Our findings suggest that CEES-induced mitochondrial ROS production and accumulation leads to mitochondrial dysfunction and inflammatory response in keratinocytes. However, treatment of antioxidants or ERK1/2 or PI3-K/Akt inhibitors is a novel therapeutic option for the keratinocytes complication.


Assuntos
Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Gás de Mostarda/análogos & derivados , Espécies Reativas de Oxigênio/metabolismo , Animais , Linhagem Celular , Substâncias para a Guerra Química/toxicidade , Dano ao DNA , DNA Mitocondrial/metabolismo , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Irritantes/toxicidade , Queratinócitos/patologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Pelados , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Gás de Mostarda/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
6.
J Photochem Photobiol B ; 205: 111824, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32126496

RESUMO

Excessive exposure to UVB radiation can lead to oxidative and inflammatory damage that compromises the cutaneous integrity. The application on the skin of photochemoprotective products is considered a relevant approach for the prevention of oxidative damage. In this study the in vitro and in vivo photochemoprotective effects of antioxidant plant materials obtained from the leaves of Nectandra cuspidata Nees following UVB irradiation were evaluated. The cytoprotective effect, reactive oxygen species (ROS) production and lipid peroxidation (LPO) were assessed in L-929 fibroblasts treated with the ethyl acetate fraction (EAF) or isolated compounds (epicatechin, isovitexin and vitexin) before or after irradiation with UVB (500 mJ/cm2). EAF substantially reduced the dead of cells and inhibited the UVB-induced ROS production and LPO in both treatments, compared with the irradiated untreated fibroblasts, presenting effects similar or better than pure compounds. The in vivo photochemoprotective effects of a topical emulsion containing 1% EAF (F2) were evaluated in hairless mice exposed to UVB. F2 improved all evaluated parameters in the skin of animals, inhibited ROS production, increased antioxidant defenses by decreasing reduced glutathione (GSH) and catalase depletion, reduced the activities of metalloproteinases (MMP-2 and MMP-9) and myeloperoxidase, decreased epidermal thickness and skin edema, and inhibited the appearance of sunburn cells as well as the recruitment of neutrophils and mast cell inflammatory infiltrates. These findings show that EAF presents high photochemoprotective effects, and that a topical formulation containing it may have potential for skin care.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Fibroblastos/efeitos dos fármacos , Lauraceae , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Protetores contra Radiação/farmacologia , Pele/efeitos dos fármacos , Raios Ultravioleta/efeitos adversos , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Feminino , Fibroblastos/efeitos da radiação , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Camundongos Pelados , Folhas de Planta , Espécies Reativas de Oxigênio/metabolismo , Pele/metabolismo , Pele/patologia , Pele/efeitos da radiação
7.
J Photochem Photobiol B ; 205: 111847, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32172138

RESUMO

The study of causes and cures for ultraviolet B radiation (UVB)-induced non-melanoma skin cancers (NMSC) has been greatly facilitated by use of the albino SKH-1 hairless mice. These mice develop multiple tumors of different sizes and the severity of cancer is often measured by one or more of the four criteria, namely the prevalence, multiplicity, area and volume of tumors. However, there are inherent limitations of each criterion: the prevalence and number do not account for size differences among tumors, area measurement ignores the tumor height, and volume measurement overcompensates for the height at the cost of planar dimensions. Here, using our dataset from an ongoing NMSC study, we discuss the limitations of these four criteria, and suggest refinements in measuring prevalence. We recommend the use of three more criteria, namely the Knud Thomsen tridimensional surface that apportions optimal weightage to three tumor dimensions, weekly occurrence of new tumors and tumor growth-rate to reveal initiation and growth of tumors in early and late phase of NMSC development, respectively. Together, use of this comprehensive panel of seven criteria can provide an accurate assessment of severity of NMSC and lead to a testable hypothesis whether the experimental manipulation of mice has affected the early initiation or growth phase of NMSC tumors.


Assuntos
Índice de Gravidade de Doença , Neoplasias Cutâneas/etiologia , Raios Ultravioleta/efeitos adversos , Animais , Camundongos Pelados , Neoplasias Cutâneas/patologia , Carga Tumoral
8.
Nutrients ; 12(2)2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31979027

RESUMO

The efficacy of wheat extract oil (WEO), standardized to glucosylceramides, for protecting against ultraviolet B (UVB)-induced damage of skin barrier function was assessed using the SHK-1 hairless mouse model and two human skin cell lines, namely, CCD-986sk and HeCaT. The ability of repeated oral administration of 30, 60, and 120 mg of WEO/kg/day for 12 weeks to prevent skin damage of SKH-1 hairless mice induced by UVB irradiation was evaluated. The results demonstrated that UVB-induced water evaporation (transepidermal water loss, TEWL) was significantly decreased by WEO. Similarly, UVB-induced losses in moisture and skin elasticity were improved by WEO supplementation. WEO attenuated the tissue procollagen type I, hyaluronic acid (HA), and ceramide reductions induced by UVB treatment as well. Collagen concentrations in skin tissue were increased in the WEO-treated mice, while UVB-induced epidermal thickening was reduced. In vitro studies using HeCaT human keratinocytes confirmed increased HA and collagen synthesis in response to WEO treatment. This may occur via WEO suppression of matrix metallopeptidase-1 (MMP-1), since its induction by UVB treatment was diminished in treated CCD-986sk cells. Oral administration of WEO improves skin barrier function in UVB-irradiated mice by attenuating damage typically observed in photoaging. This research further clarifies the clinical benefits previously observed by dietary WEO consumption.


Assuntos
Colágeno/biossíntese , Transtornos de Fotossensibilidade/tratamento farmacológico , Óleos Vegetais/farmacologia , Envelhecimento da Pele/efeitos dos fármacos , Triticum/química , Animais , Humanos , Queratinócitos/metabolismo , Camundongos , Camundongos Pelados , Transtornos de Fotossensibilidade/etiologia , Envelhecimento da Pele/efeitos da radiação , Raios Ultravioleta/efeitos adversos
9.
Toxicol Lett ; 319: 256-263, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31639410

RESUMO

Transcription factor activator protein (AP)-1 can be activated in nitrogen-mustard-injured mouse skin, and is thought to participate in the inflammatory response. AP-1 consists of homo- or heterodimers of Fos [c-Fos, Fos-B, fos-related antigen (Fra)-1 and Fra-2] and Jun (c-Jun, JunB and JunD) family members, and information about their expression, location and function are still unclear. In nitrogen-mustard-exposed mouse skin, we found p-ERK activation increased Fra-1 and FosB. Unlike the nucleus location of c-Fos and FosB, Fra-1 and Fra-2 were mainly expressed in the cytoplasm. In nitrogen-mustard-exposed cultured immortalized human keratinocytes (HaCaT cells), Fra-1 in the nucleus functioned as an inhibitor of inflammatory cytokine interleukin (IL)-8. Co-immunoprecipitation showed that Fra-1 formed dimers with IL-8 transcription factors c-Jun, JunB and JunD. Fra-1 depletion increased c-Fos and FosB in the nucleus, accompanied by increased heterodimers of c-Fos/c-Jun, c-Fos/JunB, c-Fos/JunD, and FosB/JunB. In conclusion, Fra-1 trapped in the cytoplasm after nitrogen mustard exposure might be a driving force for IL-8 over-expression in injured skin.


Assuntos
Substâncias para a Guerra Química/toxicidade , Epiderme/lesões , Epiderme/metabolismo , Interleucina-8/biossíntese , Mecloretamina/toxicidade , Proteínas Proto-Oncogênicas c-fos/metabolismo , Animais , Linhagem Celular , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Citoplasma/efeitos dos fármacos , Citoplasma/metabolismo , Humanos , Queratinócitos/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos , Camundongos Pelados , RNA Interferente Pequeno/farmacologia
10.
Life Sci ; 241: 117148, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31830478

RESUMO

Mitochondria are fascinating structures of the cellular compartments that generate energy to run the cells. However, inherent disorders of mitochondria due to diabetes can cause major disruption of metabolism that produces huge amount of reactive oxygen species (ROS). Here we study the elevated level of ROS provoked by high glucose (HG) environment triggered mitochondrial dysfunction, inflammatory response and apoptosis via stress signalling pathway in keratinocytes. Our results demonstrated that elevated glucose level in keratinoctes, increase the accumulations of ROS and decrease in cellular antioxidant capacities. Moreover, excess production of ROS was associated with mitochondrial dysfunction, characterized by loss of mitochondrial membrane potential (ΔΨm), increase in mitochondrial mass, alteration of mitochondrial respiratory complexes, cytochrome c (Cyt c) release, decrease in mitochondrial transcription factor A (TFAM) and increase in mitochondrial DNA (mtDNA) fragmentation. Damaged mtDNA escaped into the cytosol, where it engaged the activation of ERK1/2, PI3K/Akt, tuberin and mTOR via cGAS-STING leading to IRF3 activation. Pre-treatment of pharmacological inhibitors, ERK1/2 or PI3K/Akt suppressed the IRF3 activation. Furthermore, our results demonstrated that activation of IRF3 in HG environment coinciding with increased expression of inflammatory mediators. Excess production of ROS interfered with decreased in cell viability, increased lysosomal content and expression of FoxOs, leading to cell cycle deregulation and apoptosis. Pre-treatment of N-acetyl-l-cysteine (NAC) significantly reduced the HG-induced cell cycle deregulation and apoptosis in keratinocytes. In conclusion, increased oxidative stress underlies the decrease in antioxidant capacities and mitochondrial dysfunction in HG environment correlate with inflammation response and apoptosis via ERK1/2-PI3K/Akt-IRF3 pathway in keratinoctes.


Assuntos
Glucose/farmacologia , Queratinócitos/patologia , Mitocôndrias/patologia , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Pelados , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Edulcorantes/farmacologia
11.
Toxicol Appl Pharmacol ; 386: 114844, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31785243

RESUMO

When the human skin is chronically exposed to external stimuli such as ultraviolet (UV) radiation, the skin tissue suffers damage and the structure of the extracellular matrix (ECM) in the skin is disrupted. This eventually causes symptoms such as wrinkles loss of elasticity, skin sagging, and skin cancer. We previously found that hydrolysate extracted from pacific oyster (Crassostrea gigas) is effective in improving wrinkle formation. In this study, we selected a pentapeptide that was expected to have the most wrinkle reduction effect among the various peptides in oyster hydrolysate through preliminary in vitro screening and examined whether the pentapeptide derived from oyster hydrolysate (OHP) is effective in reducing wrinkles in vivo. We investigated the wrinkle-reducing effect of the OHP through 18-week SKH-1 hairless mice model. Our results showed that the OHP reduces wrinkles lengths, depths, and epidermal thickness which were increased by UVB radiation, and restores the amount of collagen. The OHP recovered the activity of antioxidant enzymes and regulated the expression of proinflammatory cytokines. We also found that OHP increases the expression of type I collagen through stimulating the TGFß/Smad signaling pathway and inhibits the MMPs expression by regulating the MAPK/AP-1 signaling pathway. This study has shown that the OHP plays crucial roles in collagen production and wrinkle reduction in hairless mice and we proved the possibility of the OHP as a component for inhibiting wrinkle formation which was induced by photoaging.


Assuntos
Crassostrea/química , Peptídeos/farmacologia , Envelhecimento da Pele/efeitos dos fármacos , Animais , Colágeno Tipo I/metabolismo , Citocinas/metabolismo , Epiderme/efeitos dos fármacos , Epiderme/metabolismo , Epiderme/patologia , Feminino , Hidrólise , Hylobatidae , Camundongos , Camundongos Pelados , Peptídeos/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real , Envelhecimento da Pele/patologia
12.
Biol Pharm Bull ; 42(12): 2102-2108, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31787725

RESUMO

The poultice formulation is a patch containing a large amount of water. It is known that the water contained in the adhesive polymer layer (ADPL) of poultice affects the cooling sensation and skin permeability of the active pharmaceutical ingredient (API). In this study, we evaluated the relationship between the water content in a ketoprofen poultice formulation and the amount of time the poultice was left out at room temperature after removal from the airtight container, as well as the influence of the decreasing water content on the skin permeability of the API. After removing the poultice from the container for 1 h, the mass of the ADPL decreased by approximately 40%. When the near-infrared (NIR) spectrum of the ADPL of poultice was measured, the peaks reflecting the hydroxyl group were attenuated depending on the time left out at room temperature. It is suggested that the changes in the mass and NIR spectrum of the ADPL are caused by the change in the water content. Moreover, when the permeability of API was evaluated on hairless mouse skin, the cumulative skin permeation amount and flux decreased, while the lag time was prolonged as the time left out increased. These results suggest that the skin permeability of the API is impaired by water evaporation and that maintaining the water in the ADPL in poultice is very important from not only the viewpoint of cooling sensation, tackiness and moisturizing but also the skin permeability of the API.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Cetoprofeno/administração & dosagem , Cetoprofeno/química , Pele/metabolismo , Adesivo Transdérmico , Água/análise , Animais , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Técnicas In Vitro , Camundongos Pelados , Permeabilidade , Absorção Cutânea , Temperatura
13.
Zhongguo Zhong Yao Za Zhi ; 44(21): 4677-4684, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31872664

RESUMO

Chinese herbal medicine ultrafine powder has become a research hotspot for the addition of cosmetic raw materials. Dendrobium candidum is a traditional Chinese herbal medicine. Its extract and stem extract are already cosmetic raw materials and its water extract has the effect of preventing photoaging,but D. candidum ultrafine powder has not been accepted as a raw material for cosmetics,and no relevant research on photoaging prevention has been reported. In this experiment,the ultra-fine powder and fine powder of D. candidum to prevent photoaging were observed and compared,and its mechanism of action was discussed to provide a basis for the prevention of skin photoaging products. Seventy-two female ICR mice were randomly divided into normal group,model group,solvent group,titanium dioxide(Ti O2) group,isooctyl salicylate(2-ES) group,D. candidum ultrafine powder 1(DP1),ultrafine powder 2(DP2) and fine powder(DP3) groups. The photoaging model was established by ultraviolet irradiation for 8 weeks,and the model was intervened while modeling. The skin wrinkle grade,elastic parameters,skin microcirculation blood flow,skin structure and pathological changes(skin thickness,skin collagen fiber,elastic fiber) were observed,the skin transforming growth factor-ß1(TGF-ß1),Smad3 levels were determined,and the type Ⅰ and type Ⅲ collagen,matrix metalloproteinase-1(MMP-1),activated protein-1(AP-1),VEGF expression were detected. The results showed that ultrafine powder(DP1,DP2) significantly reduced the wrinkle level and skin blood flow of the model mice(P<0. 05,P<0. 01); DP1,DP2 and DP3 could significantly reduce the thickness of the epidermis(P<0. 001),improve collagen fiber,elastic fiber hyperplasia,and distortion and decrease VEGF expression,and DP1 is better than DP2 and DP3; each group could up-regulate type Ⅰ collagen,down-regulate type Ⅲ collagen,AP-1,MMP-1 protein expression,and DP1 improvement optimal. However,it has no obvious effect on TGF-ß1 and Smad3. The ultrafine powder and fine powder of D. candidum have certain preventive effect on photoaging,and the effect of ultrafine powder is better than that of fine powder. Ultrafine powder may down-regulate the expression of type Ⅲ collagen,AP-1 and MMP-1 by up-regulating type Ⅰ collagen. Inhibition of collagen degradation plays a role in preventing photoaging.


Assuntos
Dendrobium , Envelhecimento da Pele , Animais , Feminino , Camundongos , Camundongos Pelados , Camundongos Endogâmicos ICR , Pele , Raios Ultravioleta
14.
J Drugs Dermatol ; 18(12): 1244-1254, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31860213

RESUMO

Lycopene, an acyclic hydrocarbon, non-provitamin A carotenoid, is a potent antioxidant with well-documented anticancer properties. In this study, we investigated the effects of dietary lycopene on sub-acute and chronic ultraviolet B (UVB)-induced skin carcinogenesis in SKH-1 mice. Groups of three mice were fed with a nonsupplemented or 1% lycopene diet for two weeks before and throughout two weeks of UVB irradiation (30 mJ/cm2 UVB, thrice weekly). The lycopene diet significantly reduced the formation of pyrimidine dimers (PDs) and the expression of proliferative cellular nuclear antigen (PCNA) in UVB-irradiated skin. Then groups of eighteen mice were each fed with control diet or with a 0.25% or 1% (w/w) lycopene-supplemented diet for 40 weeks, beginning one week before UVB irradiation (30 mJ/cm2 UVB, thrice weekly for 23 weeks) and continuing after termination of UVB. Lycopene significantly inhibited the onset and decreased the incidence, multiplicity, and tumor weights of UVB-induced skin tumors. UVB-induced epidermal hyperplasia and PCNA expression were still remarkably inhibited by dietary lycopene, even up to 40 weeks. No significant difference in protection was detected between the low and high concentrations of lycopene. These results demonstrate that dietary lycopene does protect against UVB-induced epidermal hyperplasia and carcinogenesis. J Drugs Dermatol. 2019;18(12):1244-1254.


Assuntos
Antioxidantes/administração & dosagem , Suplementos Nutricionais , Licopeno/administração & dosagem , Neoplasias Cutâneas/prevenção & controle , Animais , Antioxidantes/farmacologia , Feminino , Licopeno/farmacologia , Camundongos , Camundongos Pelados , Antígeno Nuclear de Célula em Proliferação/metabolismo , Dímeros de Pirimidina/metabolismo , Raios Ultravioleta/efeitos adversos
15.
Sci Rep ; 9(1): 19229, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31848391

RESUMO

Our aim was to develop a method to detect extramitochondrial Ca2+ movement and O2 fluxes simultaneously. Using High-Resolution FluoRespirometry, we also tested whether mitochondrial permeability transition pore (mPTP) inhibition or anoxia affects the mitochondrial Ca2+ flux. Ca2+ movement evoked by CaCl2 or anoxia was assessed with CaGreen-5N dye using Blue-Fluorescence-Sensor in isolated liver mitochondria, liver homogenates and duodenal biopsies. Exogenous CaCl2 (50 µM) resulted in an abrupt elevation in CaGreen-5N fluorescence followed by a decrease (Ca2+ uptake) with simultaneous elevation in O2 consumption in liver preparations. This was followed by a rapid increase in the fluorescence signal, reaching a higher intensity (Ca2+ efflux) than that of the initial CaCl2-induced elevation. Chelation of Ca2+ with EGTA completely abolished the fluorescence of the indicator. After pre-incubation with cyclosporin A, a marked delay in Ca2+ movement was observed, not only in isolated liver mitochondria, but also in tissue homogenates. In all samples, the transition to anoxia resulted in immediate increase in the level of extramitochondrial Ca2+. The results demonstrate that the CaGreen-5N method is suitable to monitor simultaneous O2 and Ca2+ fluxes, and the opening of mPTP in various biological samples. In this system the duration of stimulated Ca2+ fluxes may provide a novel parameter to evaluate the efficacy of mPTP blocker compounds.


Assuntos
Sinalização do Cálcio , Cálcio/metabolismo , Mitocôndrias Hepáticas/metabolismo , Consumo de Oxigênio , Animais , Corantes Fluorescentes/química , Masculino , Camundongos , Camundongos Pelados , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Ratos , Ratos Sprague-Dawley
16.
BMC Complement Altern Med ; 19(1): 286, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31660950

RESUMO

BACKGROUND: Edible insects, including Oxya chinensis sinuosa Mishchenko (Oc), which is consumed as food in Asia, are considered as a human food shortage alternative, and also as a preventive measure against environmental destruction. Ultraviolet B (UVB) irradiation, which causes skin photodamage, is considered as an extrinsic skin aging factor. It reduces skin hydration, and increases wrinkle formation and reactive oxygen species (ROS) and inflammatory cytokine expression. Thus, the objective of this study was to investigate the anti-aging effects of an ethanol extract of Oc (Oc.Ex). METHODS: A UVB-irradiated hairless mouse model was used to examine relevant changes in skin hydration, wrinkle formation, and skin epidermal thickness. Also, antioxidant markers such as superoxide dismutase (SOD) and catalase (CAT) were analyzed, and Oc. Ex skin protective effects against UVB irradiation-induced photoaging were examined by determining the levels of skin hydration factors. RESULTS: Oc.Ex improved epidermal barrier dysfunctions such as increased transepidermal water loss (TEWL) and capacitance reduction in UVB-irradiated mice. It upregulated skin hydration-related markers, including hyaluronic acid (HA), transforming growth factor (TGF)-ß, and pro-collagen, in UVB-irradiated mice, compared with the vehicle control group. It also reduced UVB-induced wrinkle formation, collagen degradation, and epidermal thickness. Additionally, it remarkably suppressed the increased expression of matrix metalloproteinases (MMPs), and restored the activity of SOD and CAT in UVB-irradiated mice, compared with the vehicle control group. Furthermore, Oc. Ex treatment downregulated the production of inflammatory cytokines and phosphorylation of the mitogen-activated protein kinases (MAPKs) signaling pathway activated by UVB irradiation. CONCLUSION: This study revealed that Oc. Ex reduced skin thickness and the degradation of collagen fibers by increasing hydration markers and collagen-regulating factors in the skin of UVB-irradiated mice. It also inhibited UVB-induced antioxidant enzyme activity and inflammatory cytokine expression via MAPK signaling downregulation, suggesting that it prevents UVB-induced skin damage and photoaging, and has potential for clinical development in skin disease treatment.


Assuntos
Gafanhotos/química , Protetores contra Radiação/farmacologia , Envelhecimento da Pele/efeitos dos fármacos , Envelhecimento da Pele/efeitos da radiação , Animais , Catalase/metabolismo , Colágeno/metabolismo , Epiderme/efeitos dos fármacos , Epiderme/metabolismo , Humanos , Masculino , Metaloproteinases da Matriz/metabolismo , Camundongos , Camundongos Pelados , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Superóxido Dismutase/metabolismo , Raios Ultravioleta/efeitos adversos
17.
Nutrients ; 11(10)2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31614689

RESUMO

Chronic and extensive exposure of ultraviolet (UV)-irradiation causes human skin sunburn, inflammation, or photoaging, which is associated with downregulated collagen synthesis. This study investigated the effects of fermented blackberry (Rubus fruticosus B., FBB) by Lactobacillus plantarum JBMI F5 (LP) on UVB-induced photoaging in human foreskin fibroblast (Hs68) as well as in SKH-1 hairless mice. FBB pretreatment inhibited UVB-mediated type-1 procollagen degradation, matrix metalloproteinase (MMP)-1 and MMP-2 protein expression, and suppressed nuclear factor-κB (NF-κB) activation as well as mitogen-activated protein kinase (MAPK) phosphorylation in Hs68. In addition, FBB administration diminished the wrinkle formation in dorsal skin and epidermal thickening in UVB-irradiated hairless mice. Moreover, UVB-induced Type-1 procollagen reduction and antioxidant enzyme inactivation were reversed by FBB administration. These results suggest that FBB may have antiphotoaging effects on UVB-induced wrinkle formation by maintaining the extracellular matrix density in the dermis, which occurs via regulation of reactive oxygen species and related MAPK and NF-κB signaling. Therefore, FBB can be a potential candidate for protecting skin aging against UV irradiation.


Assuntos
Fibroblastos/efeitos dos fármacos , Lactobacillus plantarum/metabolismo , Extratos Vegetais/farmacologia , Rubus/química , Envelhecimento da Pele/efeitos dos fármacos , Raios Ultravioleta/efeitos adversos , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Feminino , Fermentação , Fibroblastos/efeitos da radiação , Prepúcio do Pênis/citologia , Frutas/química , Masculino , Camundongos , Camundongos Pelados , Extratos Vegetais/química , Envelhecimento da Pele/efeitos da radiação
18.
Int J Biol Sci ; 15(10): 2100-2109, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31592145

RESUMO

To evaluate the photoprotective effect of 5-aminolaevulinic acid-based photodynamic therapy (ALA-PDT) on ultraviolet B (UVB)-induced skin photodamage. In vivo experiments, the dorsal skin of hairless mice were treated with ALA-PDT or saline-PDT, and then exposed to 180 mJ/m2 UVB. Results showed that the number of sunburn cells and apoptotic cells in the epidermis of ALA-PDT-treated groups at 24 h after UVB irradiation were significantly decreased compared with those in the UVB groups. And the removal rate of CPDs was obviously higher in ALA-PDT-treated groups. At 48 h, the number of Ki67 positive nuclei in ALA-PDT-UVB group was significantly fewer than that in UVB group. Further in vitro experiments, human keratinocyte cell line (HaCaT) cells of two groups (one treated with ALA-PDT, the other untreated), were exposed to 60 mJ/m2 UVB irradiation. We found 0.5 mmol/L of ALA and 3 J/cm2 of red light did not affect the vitality of cells, and could reduce UVB induced apoptosis, accelerate the clearance of CPDs, inhibit proliferation and activate p53. Thus, our data demonstrate that ALA-PDT pretreatment can induce a protective DNA damage response that protects skin cells from UVB-induced photodamages.


Assuntos
Dano ao DNA/efeitos da radiação , Ácidos Levulínicos/uso terapêutico , Fotoquimioterapia/métodos , Pele/metabolismo , Pele/efeitos da radiação , Raios Ultravioleta/efeitos adversos , Animais , Apoptose/efeitos da radiação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos da radiação , Feminino , Citometria de Fluxo , Humanos , Camundongos , Camundongos Pelados , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
19.
Nutrients ; 11(10)2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31581754

RESUMO

Our previous study showed that hydrangenol isolated from Hydrangea serrata leaves exerts antiphotoaging activity in vitro. In this study, we determined its antiphotoaging effect in UVB-irradiated HR-1 hairless mice. We evaluated wrinkle formation, skin thickness, histological characteristics, and mRNA and protein expression using qRT-PCR and Western blot analysis in dorsal skins. Hydrangenol mitigated wrinkle formation, dorsal thickness, dehydration, and collagen degradation. Hydrangenol increased the expression of involucrin, filaggrin, and aquaporin-3 (AQP3) as well as hyaluronic acid (HA) production via hyaluronidase (HYAL)-1/-2 downregulation. Consistent with the recovery of collagen composition, the expression of Pro-COL1A1 was increased by hydrangenol. Matrix metalloproteinase (MMP)-1/-3, cyclooxygenase-2 (COX-2), and interleukin-6 (IL-6) expression was reduced by hydrangenol. Hydrangenol attenuated the phosphorylation of mitogen-activated protein kinases (MAPKs) including ERK and p38, activator protein 1 (AP-1) subunit, and signal transduction and activation of transcription 1 (STAT1). Hydrangenol upregulated the expression of nuclear factor-E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO-1), glutamate cysteine ligase modifier subunit (GCLM), and glutamate cysteine ligase catalysis subunit (GCLC). Taken together, our data suggest that hydrangenol can prevent wrinkle formation by reducing MMP and inflammatory cytokine levels and increasing the expression of moisturizing factors and antioxidant genes.


Assuntos
Fármacos Dermatológicos/farmacologia , Hydrangea/química , Isocumarinas/farmacologia , Extratos Vegetais/farmacologia , Folhas de Planta/química , Envelhecimento da Pele/efeitos dos fármacos , Pele/efeitos dos fármacos , Raios Ultravioleta/efeitos adversos , Água/metabolismo , Animais , Antioxidantes/metabolismo , Colágeno Tipo I/metabolismo , Citocinas/metabolismo , Fármacos Dermatológicos/isolamento & purificação , Mediadores da Inflamação/metabolismo , Isocumarinas/isolamento & purificação , Masculino , Metaloproteinase 13 da Matriz/metabolismo , Metaloproteinase 3 da Matriz/metabolismo , Camundongos Pelados , Extratos Vegetais/isolamento & purificação , Proteólise , Transdução de Sinais , Pele/metabolismo , Pele/patologia , Pele/efeitos da radiação , Envelhecimento da Pele/efeitos da radiação
20.
J Microbiol Biotechnol ; 29(9): 1349-1360, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31474086

RESUMO

Chronic exposure to ultraviolet (UV) radiation, regarded as a major cause of extrinsic aging or photoaging characterized by wrinkle formation and skin dehydration, exerts adverse effects on skin by causing the overproduction of reactive oxygen species. Agastache rugosa Kuntze, known as Korean mint, possesses a wide spectrum of biological properties including antioxidation, anti-inflammation, and anti-atherosclerosis. Previous studies have reported that A. rugosa protected human keratinocytes against UVB irradiation by restoring the anti-oxidant defense system. However, the anti-photoaging effect of A. rugosa extract (ARE) in animal models has not yet been evaluated. ARE was orally administered to hairless mice at doses of 100 or 250 mg/kg/day along with UVB exposure for 12 weeks. ARE histologically improved UVB-induced wrinkle formation, epidermal thickening, erythema, and hyperpigmentation. In addition, ARE recovered skin moisture by improving skin hydration and transepidermal water loss (TEWL). Along with this, ARE increased hyaluronic acid levels by upregulating HA synthase genes. ARE markedly increased the density of collagen and the amounts of hydroxypoline via two pathways. First, ARE significantly downregulated the mRNA expression of matrix metalloproteinases responsible for collagen degradation by inactivating the mitogen-activated protein kinase/activator protein 1 pathway. Second, ARE stimulated the transforming growth factor beta/Smad signaling, consequently raising the mRNA levels of collagen-related genes. In addition, ARE not only increased the mRNA expression of antioxidant enzymes but also decreased inflammatory cytokines by blocking the protein expression of nuclear factor kappa B. Collectively, our findings suggest that A. rugosa may be a potential preventive and therapeutic agent for photoaging.


Assuntos
Agastache/química , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Envelhecimento da Pele/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo , Raios Ultravioleta/efeitos adversos , Animais , Antioxidantes/metabolismo , Colágeno/biossíntese , Colágeno/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Camundongos Pelados , Proteínas Quinases Ativadas por Mitógeno/genética , Fosforilação/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Pele/efeitos da radiação , Envelhecimento da Pele/patologia , Envelhecimento da Pele/efeitos da radiação , Proteínas Smad/genética , Proteínas Smad/metabolismo , Fator de Transcrição AP-1/genética , Fator de Transcrição AP-1/metabolismo , Fator de Crescimento Transformador beta/genética
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