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1.
Environ Monit Assess ; 193(12): 840, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34822005

RESUMO

UV-filters are widely used in cosmetics and personal care products to protect users' skin from redamage caused by ultraviolet (UV) radiation from the sun. Globally, an estimated 16,000 to 25,000 tonnes of products containing UV-filters were used in 2014 with modern consumption likely to be much higher. Beyond this use in cosmetics and personal care products, UV-filters are also widely used to provide UV-stability in industrial products such as paints and plastics. This review discusses the main routes by which UV-filters enter aquatic environments and summarises the conclusions of studies from the past 10 years that have investigated the effects of UV-filters on environmentally relevant species including corals, microalgae, fish, and marine mammals. Safety data regarding the potential impact of UV-filters on human health are also discussed. Finally, we explore the challenges surrounding UV-filter removal and research on more environmentally friendly alternatives to current UV-filters.


Assuntos
Cosméticos , Protetores Solares , Animais , Monitoramento Ambiental , Peixes , Humanos , Protetores Solares/análise , Protetores Solares/toxicidade , Raios Ultravioleta/efeitos adversos
2.
Vet Dermatol ; 32(6): 605-e161, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34796565

RESUMO

BACKGROUND: In human medicine, narrow-band ultraviolet B (NB-UVB) phototherapy has been used to treat various T-cell-mediated skin diseases. However, the effect of NB-UVB on inflamed canine skin remains uncertain. OBJECTIVES: To investigate the effect of NB-UVB phototherapy on the skin of dogs with hapten-induced contact dermatitis. ANIMALS: Seven healthy beagles without skin problems. METHODS AND MATERIALS: Dogs were irradiated with varying doses of NB-UVB to determine the minimal erythema dose (MED). After determining the MEDs of six dogs (excluding one of the seven whose skin did not show a visible reaction), we investigated the effect of NB-UVB on their inflamed skin by topically applying 2,4-dinitrochlorobenzene (DNCB), which causes type 1 helper T cell (Th1)- and cytotoxic T-cell (Tc)1-induced skin inflammation. We then irradiated the skin with NB-UVB. We analysed the treated skin samples via histopathological and immunohistochemical methods, and TdT-mediated dUTP nick-end labelling (TUNEL) to demonstrate apoptotic cells. We also analysed the cytokine gene transcription via real-time quantitative reverse transcription PCR. RESULTS: The NB-UVB MEDs caused mild inflammatory changes yet no severe epidermal exfoliations in the irradiated skin. In DNCB-treated skin irradiated by the NB-UVB MEDs, TUNEL-positive dermal apoptotic cells were increased significantly compared with those of DNCB-treated, nonirradiated skin. INF-γ and TNF-α transcription levels in DNCB-treated, irradiated skin were significantly lower than those in the DNCB-treated, nonirradiated skin. CONCLUSION AND CLINICAL RELEVANCE: Phototherapy using NB-UVB MEDs attenuated cutaneous Th1 and Tc1 cytokine responses with minimal skin damage in a canine model of hapten-induced contact dermatitis.


Assuntos
Dermatite de Contato , Doenças do Cão , Terapia Ultravioleta , Animais , Dermatite de Contato/veterinária , Doenças do Cão/radioterapia , Cães , Haptenos , Pele , Linfócitos T , Raios Ultravioleta/efeitos adversos , Terapia Ultravioleta/efeitos adversos , Terapia Ultravioleta/veterinária
3.
Clin Dermatol ; 39(5): 865-872, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34785014

RESUMO

Indoor tanning continues to remain common, despite evidence of an increased risk of skin cancer from artificial ultraviolet (UV) radiation. In the hopes of gaining customers, the tanning bed industry has marketed health benefits of indoor tanning such as increased vitamin D production, development of a base tan, enhanced mood, and treatment of certain dermatologic conditions. To better educate their patients, providers need a comprehensive reference reviewing the evidence that support or oppose these claims. In this work, we conducted an evidence-based review of the literature to identify and grade studies that investigate health claims related to UV exposure. Results indicate that there is little evidence to support each of these proposed health benefits. Tanning beds emit primarily UVA radiation, which is relatively ineffective at activating vitamin D or mood enhancing pathways, and the effects are minimal in regard to tanning beds generating a protective base tan or treating dermatologic conditions compared with the increased risk of skin cancer. Health care providers must continue to warn and educate patients about the misleading information propagated by the tanning bed industry as well as about the dangers of artificial UV radiation.


Assuntos
Neoplasias Cutâneas , Banho de Sol , Humanos , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/prevenção & controle , Raios Ultravioleta/efeitos adversos , Vitamina D
4.
Ecotoxicol Environ Saf ; 227: 112892, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34649141

RESUMO

Exposure to ultraviolet B (UVB) has been demonstrated to induce DNA damage as well as angiogenesis-related photo-damages, which are implicated in a variety of medical problems, including sunburn, photo-aging and skin cancers. However, the molecular mechanism related to UVB-induced photo-injuries remained fully elucidated. Here we revealed that one of the catalytic subunits of the IKK complex, IKKα, played a critical role in mediating UVB-induced apoptotic responses in two kinds of UVB sensitive cells, human keratinocyte (HaCat) and mouse embryonic fibroblasts (MEFs). This function of IKKα was unrelated to NF-κB activity, but was delivered by inducing phosphorylation and acetylation of p53 and upregulating the expression of the pro-apoptotic p53 target gene, PERP. Although IKKα kinase activity was required for mediating post-translational modifications and transactivation of 53 and PERP induction, IKKα did not show direct binding ability toward p53. Instead, IKKα could interact with CHK1, the protein kinase leading to p53 phosphorylation, and trigger CHK1 activation and CHK1/p53 complex formation. At the same time, IKKα could also interact with p300 and CBP, the acetyltransferases responsible for p53 acetylation, and trigger p300/CBP activation and p300/p53 or CBP/p53 complex formation under UVB exposure. Taken together, we have identified a novel NF-κB-independent role of IKKα in mediating UVB-induced apoptosis by regulating p53 pathway activation. Targeting IKKα/p53/PERP pathway might be helpful to prevent skin photo-damages induced by sunlight.


Assuntos
Proteína Supressora de Tumor p53 , Raios Ultravioleta , Animais , Apoptose , Fibroblastos/metabolismo , Genes Supressores de Tumor , Humanos , Quinase I-kappa B , Queratinócitos , Proteínas de Membrana , Camundongos , NF-kappa B/genética , NF-kappa B/metabolismo , Proteína Supressora de Tumor p53/genética , Raios Ultravioleta/efeitos adversos
6.
J Cosmet Laser Ther ; 23(1-2): 1-7, 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-34669525

RESUMO

Social distancing is conducive to grow the impact of artificial light in the daily life of the worldwide population with reported consequences to the skin. Sunlight is also essential for human development, indeed, solar radiation is composed of different types of wavelengths, which generate different skin effects. It can be divided into ultraviolet (UV), infrared (IR), and visible. UV radiation (UVA and UVB) has cutaneous biological effects ranging from photoaging, immunosuppression to melanoma formation, through the production of reactive oxygen species (ROS), inflammation and elevation of the energy state of organic molecules, changing the DNA structure. IR radiation reaches deeper layers of the skin and is also related to the generation of ROS, photoaging and erythema while visible light is responsible for generating ROS, pigmentation, cytokine formation, and matrix metallopeptidases (MMPs). Furthermore, artificial light could be harmful to the skin, as it can generate ROS, hyperpigmentation, and stimulate photoaging. Currently, we briefly summarized the cutaneous biological effects of sunlight, as well as artificial light on skin and remarked the opportunity of the evolution of current photoprotective formulas through new strategies with broad spectrum protection.


Assuntos
Pele , Protetores Solares , Humanos , Raios Infravermelhos , Luz Solar , Raios Ultravioleta/efeitos adversos
8.
Arch Environ Contam Toxicol ; 81(3): 507-516, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34545442

RESUMO

Coastal marine microalgae are exposed to anthropogenic pollutants, including pesticides from aquaculture/agriculture/household uses. Some microalgae species, such as Phaeodactylum tricornutum, can induce and accumulate UV-absorbing compounds (UACs) upon ultraviolet radiation (UVR) exposure to prevent deleterious effects. Tolerance mechanisms activated by natural stressors might also protect organisms from anthropogenic stressors. This work assesses the effects of the insecticide cypermethrin (Cyp) and UVR in the marine microalgae P tricornutum. Considering the pro-oxidant properties of both stressors and UACs' induction in P tricornutum, lethal and sublethal effects of Cyp were tested in cultures with and without UVR acclimation. After a 24-h exposure to 10 µg L-1 of technical Cyp or culture medium, UACs, growth, glutathione-S-transferase activity (GST), sulfhydryl groups (SH-g), and lipid peroxidation (LPO) were analyzed. Results showed differences in terms of growth between Cyp and Cyp + UVR pre-exposure. UACs' content was induced after UVR acclimation and diminished after 24 h of growth in control and UVR pre-treated cultures, while levels remained constant under Cyp exposure. A single Cyp exposure exerted GST induction, SH-g depletion, and LPO increments. In UVR-acclimatized treatments, oxidative stress responses showed similar or more pronounced effects than the single chemical exposure, suggesting a potential additive effect of the UVR acclimation. The contrasting effects of Cyp + UVR observed between growth and biochemical responses suggest different compensatory mechanisms that need to be further investigated. Also, it highlights the need to include both lethal and sublethal endpoints to understand microalgae's tolerance and its significance in the multiple stressors' context.


Assuntos
Diatomáceas , Microalgas , Piretrinas , Piretrinas/toxicidade , Raios Ultravioleta/efeitos adversos
9.
Clin Plast Surg ; 48(4): 543-550, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34503715

RESUMO

In the Western population, 1 out of every 50 individuals will develop melanoma. The incidence of melanoma is increasing faster than any other malignancy. The development of melanoma is multifactorial arising from an interaction between genetic susceptibility and environmental exposures. Sixty to seventy percent of melanomas are thought to be caused by ultraviolet radiation. Most cutaneous melanomas are of increased risk. Prevention strategies involve mitigating the environmental risk factors and identifying individuals with phenotypic risk factors for increased surveillance.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Incidência , Melanoma/epidemiologia , Melanoma/etiologia , Melanoma/prevenção & controle , Fatores de Risco , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/prevenção & controle , Raios Ultravioleta/efeitos adversos
10.
Redox Biol ; 47: 102143, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34592565

RESUMO

The ultraviolet B radiation (UVB) causes skin inflammation, which contributes to the causality and the exacerbation of a number of cutaneous diseases. However, the mechanism of UVB-driven inflammation in the skin remains poorly understood. We show that ferroptosis, a non-apoptotic programmed cell death pathway that is promoted by an excessive phospholipid peroxidation, is activated in the epidermal keratinocytes after their exposure to UVB. The susceptibility of the keratinocytes to UVB-induced ferroptosis depends on the extent of pro-ferroptosis death signal generation and the dysregulation of the glutathione system. Inhibition of ferroptosis prevents the release of HMGB1 from the human epidermal keratinocytes, and blocks necroinflammation in the UVB-irradiated mouse skin. We show that while apoptosis and pyroptosis are also detectable in the keratinocytes after UVB exposure, ferroptosis plays a significant role in initiating UVB-induced inflammation in the skin. Our results have important implications for the prevention and the treatment of a broad range of skin diseases which are fostered by UVB-induced inflammation.


Assuntos
Ferroptose , Animais , Apoptose , Inflamação , Queratinócitos , Camundongos , Pele , Raios Ultravioleta/efeitos adversos
11.
Dev Cell ; 56(18): 2547-2561.e8, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34473941

RESUMO

Ultraviolet (UV) radiation is a prime environmental stressor that our epidermis is exposed to on a daily basis. To avert UV-induced damage, epidermal stem cells (EpSCs) become pigmented via a process of heterotypic interaction between melanocytes and EpSCs; however, the molecular mechanisms of this interaction are not well understood. In this study, we show that the function of a key chromatin regulator, the Polycomb complex, was reduced upon UV exposure in human and mouse epidermis. Genetic ablation of key Polycomb subunits in murine EpSCs, mimicking depletion upon UV exposure, results in an increased number of epidermal melanocytes and subsequent epidermal pigmentation. Genome-wide transcriptional and chromatin studies show that Polycomb regulates the expression of UV-responsive genes and identifies type II collagen (COL2A1) as a critical secreted regulator of melanogenesis and epidermal pigmentation. Together, our findings show how UV exposure induces Polycomb-mediated changes in EpSCs to affect melanocyte behavior and promote epidermal pigmentation.


Assuntos
Células Epidérmicas/citologia , Epiderme/metabolismo , Melanócitos/metabolismo , Células-Tronco/citologia , Animais , Células Cultivadas , Epiderme/patologia , Queratinócitos/metabolismo , Camundongos Transgênicos , Pigmentação/fisiologia , Pigmentação da Pele/fisiologia , Raios Ultravioleta/efeitos adversos
12.
Front Public Health ; 9: 666528, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34368047

RESUMO

Ultraviolet radiation (UVR) is a known carcinogen participated for the development of skin cancers. Solar UVR exposure, particularly ultraviolet B (UVB), is the mostly significant environmental risk factor for the occurrence and progress of basal cell carcinoma(BCC). Both cumulative and intermittent high-grade UVR exposure could promote the uncontrolled replication of skin cells. There are also exsiting other contributing environmental factors that combine with the UVR exposure to promote the development of BCC. DNA damage in formation of skin cancers is considered to be a result of UVR toxicity. It is UVR that could activate a series of oncogenes simultaneously inactivating tumor suppressor genes and aberrant proliferation and survival of keratinocytes that repair these damages. Furthermore, mounting evidence demonstrates that inflammatory responses of immune cells in the tumor microenvironment plays crucial role in the skin tumorigenesis as well. In this chapter, we will follow the function of UVR in the onset and development of BCC. We describe the factors that influence BCC induced by UVR, and also review the recent advances of pathogenesis of BCC induced by UVR from the genetic and inflammatory aspects.


Assuntos
Carcinoma Basocelular , Neoplasias Cutâneas , Carcinoma Basocelular/epidemiologia , Humanos , Pele , Neoplasias Cutâneas/epidemiologia , Luz Solar , Microambiente Tumoral , Raios Ultravioleta/efeitos adversos
13.
Am J Hum Genet ; 108(9): 1611-1630, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34343493

RESUMO

Genome-wide association studies (GWASs) have identified a melanoma-associated locus on chromosome band 7p21.1 with rs117132860 as the lead SNP and a secondary independent signal marked by rs73069846. rs117132860 is also associated with tanning ability and cutaneous squamous cell carcinoma (cSCC). Because ultraviolet radiation (UVR) is a key environmental exposure for all three traits, we investigated the mechanisms by which this locus contributes to melanoma risk, focusing on cellular response to UVR. Fine-mapping of melanoma GWASs identified four independent sets of candidate causal variants. A GWAS region-focused Capture-C study of primary melanocytes identified physical interactions between two causal sets and the promoter of the aryl hydrocarbon receptor (AHR). Subsequent chromatin state annotation, eQTL, and luciferase assays identified rs117132860 as a functional variant and reinforced AHR as a likely causal gene. Because AHR plays critical roles in cellular response to dioxin and UVR, we explored links between this SNP and AHR expression after both 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and ultraviolet B (UVB) exposure. Allele-specific AHR binding to rs117132860-G was enhanced following both, consistent with predicted weakened AHR binding to the risk/poor-tanning rs117132860-A allele, and allele-preferential AHR expression driven from the protective rs117132860-G allele was observed following UVB exposure. Small deletions surrounding rs117132860 introduced via CRISPR abrogates AHR binding, reduces melanocyte cell growth, and prolongs growth arrest following UVB exposure. These data suggest AHR is a melanoma susceptibility gene at the 7p21.1 risk locus and rs117132860 is a functional variant within a UVB-responsive element, leading to allelic AHR expression and altering melanocyte growth phenotypes upon exposure.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Carcinoma de Células Escamosas/genética , Cromossomos Humanos Par 7 , Loci Gênicos , Melanócitos/metabolismo , Melanoma/genética , Receptores de Hidrocarboneto Arílico/genética , Neoplasias Cutâneas/genética , Alelos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinogênese/patologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Cromatina/química , Cromatina/metabolismo , Regulação da Expressão Gênica , Predisposição Genética para Doença , Genoma Humano , Estudo de Associação Genômica Ampla , Humanos , Melanócitos/efeitos dos fármacos , Melanócitos/patologia , Melanócitos/efeitos da radiação , Melanoma/metabolismo , Melanoma/patologia , Dibenzodioxinas Policloradas/toxicidade , Polimorfismo de Nucleotídeo Único , Cultura Primária de Células , Regiões Promotoras Genéticas , Receptores de Hidrocarboneto Arílico/metabolismo , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Banho de Sol , Raios Ultravioleta/efeitos adversos
14.
Invest Ophthalmol Vis Sci ; 62(10): 6, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34369985

RESUMO

Purpose: Toll-like receptor 3 (TLR3), as a damage-associated molecular pattern sensor, can detect self-RNA released from necrotic cells induced by ultraviolet B (UVB) radiation exposure. Pterygium formation is believed to be a tumorigenesis-like process induced by UVB exposure. In this study, we aimed to investigate the expression pattern of TLR3 in pterygium specimens and cultured pterygial epithelial cells (PECs). Methods: Human pterygium and ipsilateral pterygium-free conjunctiva from the same patients were used in this study. The expression of TLR3 and nuclear factor-kappa B (NF-κB) was investigated in these specimens. PECs were exposed to UVB radiation to determine the effect of UVB on the expression of TLR3 and the activation of NF-κB. Results: The immunofluorescence study showed stronger TLR3 expression in superficial epithelial cells in the pterygial epithelium in comparison with the normal conjunctival epithelium. The expression of TLR3 decreased in intensity from the superficial epithelium toward the basal cell layer, implying a correlation between UVB exposure and TLR3 expression. Differential TLR3 expression patterns in pterygial and conjunctival tissues were also found in quantitative PCR analyses. PECs after UVB irradiation had higher protein levels of TLR3 and phospho-NF-κB than those of the PECs without irradiation. Immunofluorescence studies showed that UVB irradiation induced the nuclear translocation of NF-κB in the PECs. In PECs with the targeted TLR3 gene silencing, the expression of phospho-NF-κB was not induced by UVB irradiation. Conclusions: Our results indicate that UVB exposure, TLR3 expression, and NF-κB activation may be a critical sequence that leads to the formation of pterygium.


Assuntos
Túnica Conjuntiva/metabolismo , Regulação da Expressão Gênica , Pterígio/genética , RNA/genética , Receptor 3 Toll-Like/genética , Células Cultivadas , Túnica Conjuntiva/patologia , Seguimentos , Humanos , Imuno-Histoquímica , Pterígio/etiologia , Pterígio/patologia , Estudos Retrospectivos , Transdução de Sinais , Receptor 3 Toll-Like/biossíntese , Raios Ultravioleta/efeitos adversos
15.
Photochem Photobiol Sci ; 20(9): 1229-1238, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34449075

RESUMO

Photoaging induced by both ultraviolet and visible light has been shown to lead to increased inflammation and dysregulation of the extracellular matrix. Standardized extract of the Polypodium leucotomos fern, PLE, possesses anti-inflammatory and antioxidant properties, and has been shown to potentially mitigate photoaging through various mechanisms. This comprehensive review presents the data available on the effects of P. leucotomos extract on UV and VL-induced photoaging in vitro as well as in vivo in murine and human models.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Extratos Vegetais/farmacologia , Polypodium , Envelhecimento da Pele/efeitos dos fármacos , Protetores Solares/farmacologia , Animais , Anti-Inflamatórios/química , Antioxidantes/química , Humanos , Luz/efeitos adversos , Extratos Vegetais/química , Polypodium/química , Pele/efeitos dos fármacos , Pele/efeitos da radiação , Protetores Solares/química , Raios Ultravioleta/efeitos adversos
16.
Int J Mol Sci ; 22(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34360928

RESUMO

Xeroderma Pigmentosum protein C (XPC) is involved in recognition and repair of bulky DNA damage such as lesions induced by Ultra Violet (UV) radiation. XPC-mutated cells are, therefore, photosensitive and accumulate UVB-induced pyrimidine dimers leading to increased cancer incidence. Here, we performed a high-throughput screen to identify chemicals capable of normalizing the XP-C phenotype (hyper-photosensitivity and accumulation of photoproducts). Fibroblasts from XP-C patients were treated with a library of approved chemical drugs. Out of 1280 tested chemicals, 16 showed ≥25% photo-resistance with RZscore above 2.6 and two drugs were able to favor repair of 6-4 pyrimidine pyrimidone photoproducts (6-4PP). Among these two compounds, Isoconazole could partially inhibit apoptosis of the irradiated cells especially when cells were post-treated directly after UV irradiation while Clemizole Hydrochloride-mediated increase in viability was dependent on both pre and post treatment. No synergistic effect was recorded following combined drug treatment and the compounds exerted no effect on the proliferative capacity of the cells post UV exposure. Amelioration of XP-C phenotype is a pave way towards understanding the accelerated skin cancer initiation in XP-C patients. Further examination is required to decipher the molecular mechanisms targeted by these two chemicals.


Assuntos
Benzimidazóis/farmacologia , Miconazol/análogos & derivados , Dermatopatias/tratamento farmacológico , Raios Ultravioleta/efeitos adversos , Xeroderma Pigmentoso/tratamento farmacológico , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Reposicionamento de Medicamentos , Humanos , Miconazol/farmacologia
17.
J Vis Exp ; (173)2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34369925

RESUMO

This article describes the methods of measuring the toxicity of ultraviolet (UV) radiation and ocular toxins on primary (pHCEC) and immortalized (iHCEC) human corneal epithelial cell cultures. Cells were exposed to UV radiation and toxic doses of benzalkonium chloride (BAK), hydrogen peroxide (H2O2), and sodium dodecyl sulfate (SDS). Metabolic activity was measured using a metabolic assay. The release of inflammatory cytokines was measured using a multi-plex interleukin (IL)-1ß, IL-6, IL-8, and tumor necrosis factor-alpha (TNF-α) assay, and cells were evaluated for viability using fluorescent dyes. The damaging effects of UV on cell metabolic activity and cytokine release occurred at 5 min of UV exposure for iHCEC and 20 min for pHCEC. Similar percent drops in metabolic activity of the iHCEC and pHCEC occurred after exposure to BAK, H2O2, or SDS, and the most significant changes in cytokine release occurred for IL-6 and IL-8. Microscopy of fluorescently stained iHCEC and pHCEC BAK-exposed cells showed cell death at 0.005% BAK exposure, although the degree of ethidium staining was greater in the iHCECs than pHCECs. Utilizing multiple methods of assessing toxic effects using microscopy, assessments of metabolic activity, and cytokine production, the toxicity of UV radiation and chemical toxins could be determined for both primary and immortalized cell lines.


Assuntos
Epitélio Corneano , Raios Ultravioleta , Compostos de Benzalcônio , Células Epiteliais , Humanos , Peróxido de Hidrogênio , Raios Ultravioleta/efeitos adversos
18.
Molecules ; 26(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34361703

RESUMO

Matrix metalloproteinases (MMPs) are the family of proteases that are mainly responsible for degrading extracellular matrix (ECM) components. In the skin, the overexpression of MMPs as a result of ultraviolet radiation triggers an imbalance in the ECM turnover in a process called photoaging, which ultimately results in skin wrinkling and premature skin ageing. Therefore, the inhibition of different enzymes of the MMP family at a topical level could have positive implications for photoaging. Considering that the MMP catalytic region is mostly conserved across different enzymes of the MMP family, in this study we aimed to design a virtual screening (VS) workflow to identify broad-spectrum MMP inhibitors that can be used to delay the development of photoaging. Our in silico approach was validated in vitro with 20 VS hits from the Specs library that were not only structurally different from one another but also from known MMP inhibitors. In this bioactivity assay, 18 of the 20 compounds inhibit at least one of the assayed MMPs at 100 µM (with 5 of them showing around 50% inhibition in all the tested MMPs at this concentration). Finally, this VS was used to identify natural products that have the potential to act as broad-spectrum MMP inhibitors and be used as a treatment for photoaging.


Assuntos
Inibidores de Metaloproteinases de Matriz/farmacologia , Metaloproteinases da Matriz/química , Pele/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/farmacologia , Produtos Biológicos/química , Domínio Catalítico , Ensaios Enzimáticos , Ensaios de Triagem em Larga Escala , Humanos , Inibidores de Metaloproteinases de Matriz/química , Metaloproteinases da Matriz/metabolismo , Simulação de Acoplamento Molecular , Ligação Proteica , Conformação Proteica , Domínios e Motivos de Interação entre Proteínas , Sensibilidade e Especificidade , Pele/enzimologia , Pele/patologia , Pele/efeitos da radiação , Envelhecimento da Pele/efeitos dos fármacos , Envelhecimento da Pele/efeitos da radiação , Bibliotecas de Moléculas Pequenas/química , Eletricidade Estática , Relação Estrutura-Atividade , Raios Ultravioleta/efeitos adversos , Interface Usuário-Computador
19.
Redox Biol ; 46: 102110, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34418602

RESUMO

Ultraviolet (UV) B irradiation of keratinocytes results in the formation of the tryptophan photoproduct 6-formylindolo[3,2-b]carbazole (FICZ) which is a high-affinity ligand for the aryl hydrocarbon receptor (AHR). The resulting activation of AHR signaling induces the expression of cytochrome P450 (CYP) 1A1 which subsequently metabolizes FICZ. Importantly, FICZ is also a nanomolar photosensitizer for UVA radiation. Here, we assess whether a manipulation of the AHR-CYP1A1 axis in human epidermal keratinocytes affects FICZ/UVA-induced phototoxic effects and whether this interaction might be mechanistically relevant for the phototoxicity of the BRAF inhibitor vemurafenib. Treatment of keratinocytes with an AHR agonist enhanced the CYP1A1-catalyzed metabolism of FICZ and thus prevented UVA photosensitization, whereas an inhibition of either AHR signaling or CYP1A1 enzyme activity resulted in an accumulation of FICZ and a sensitization to UVA-induced oxidative stress and apoptosis. Exposure of keratinocytes to vemurafenib resulted in the same outcome. Specifically, CYP phenotyping revealed that vemurafenib is primarily metabolized by CYP1A1 and to a lesser degree by CYP2J2 and CYP3A4. Hence, vemurafenib sensitized keratinocytes to UVA-induced apoptosis by interfering with the CYP1A1-mediated oxidative metabolism of FICZ. In contrast to this pro-apoptotic effect, a treatment of UVB-damaged keratinocytes with vemurafenib suppressed apoptosis, a process which might contribute to the skin carcinogenicity of the drug. Our results provide insight into the mechanisms responsible for the photosensitizing properties of vemurafenib and deliver novel information about its metabolism which might be relevant regarding potential drug-drug interactions. The data emphasize that the AHR-CYP1A1 axis contributes to the pathogenesis of cutaneous adverse drug reactions.


Assuntos
Queratinócitos , Receptores de Hidrocarboneto Arílico , Apoptose , Carbazóis , Humanos , Raios Ultravioleta/efeitos adversos , Vemurafenib
20.
Glob Chang Biol ; 27(22): 5681-5683, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34392574

RESUMO

The Montreal Protocol and its Amendments have been highly effective in protecting the stratospheric ozone layer, preventing global increases in solar ultraviolet-B radiation (UV-B; 280-315 nm) at Earth's surface, and reducing global warming. While ongoing and projected changes in UV-B radiation and climate still pose a threat to human health, food security, air and water quality, terrestrial and aquatic ecosystems, and construction materials and fabrics, the Montreal Protocol continues to play a critical role in protecting Earth's inhabitants and ecosystems by addressing many of the United Nations Sustainable Development Goals.


Assuntos
Perda de Ozônio , Ozônio , Mudança Climática , Ecossistema , Humanos , Ozônio Estratosférico , Raios Ultravioleta/efeitos adversos
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