RESUMO
OBJECTIVES: To evaluate the effects of a topical emulsion containing pyrrolidine dithiocarbamate (PDTC) (EcPDTC) in skin oxidative stress and inflammation triggered by ultraviolet B (UVB) irradiation (dose of 4.14 J/cm2 ). METHODS: Hairless mouse received treatment with 0.5 g of EcPDTC or control emulsion (CTRLE) on the dorsal surface skin 12 h, 6 h and 5 min before and 6 h after the irradiation. Oxidative stress was evaluated by ferric reducing antioxidant power (FRAP), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radical (ABTS) scavenging capacity, reduced glutathione quantitation, catalase activity, superoxide anion production and lipid peroxidation products. Inflammation parameters were as follows: skin oedema, myeloperoxidase activity (neutrophil marker), matrix metalloproteinase-9 activity, collagen fibre damage, mast cell and sunburn cell counts, and cytokine production. KEY FINDINGS: Topical treatment with EcPDTC protected from UVB-induced skin injury by maintaining the antioxidant capacity levels similar to non-irradiated control group. Furthermore, EcPDTC inhibited UVB irradiation-induced superoxide anion production, lipid peroxidation and reduced skin inflammation by inhibiting skin oedema, neutrophil recruitment, metalloproteinase-9 activity, collagen fibre damage, mast cell and sunburn cell counts, and cytokine (TNF-α and IL-1ß) production. CONCLUSIONS: Topical treatment with EcPDTC improves antioxidant systems and inhibits inflammation, protecting the skin from the damaging effects of UVB irradiation.
Assuntos
Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Pirrolidinas/administração & dosagem , Pele/efeitos dos fármacos , Queimadura Solar/prevenção & controle , Tiocarbamatos/administração & dosagem , Raios Ultravioleta , Administração Cutânea , Animais , Anti-Inflamatórios/química , Antioxidantes/química , Citocinas/metabolismo , Modelos Animais de Doenças , Composição de Medicamentos , Emulsões , Mediadores da Inflamação/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos Pelados , Estresse Oxidativo/efeitos dos fármacos , Pirrolidinas/química , Pele/metabolismo , Pele/patologia , Queimadura Solar/metabolismo , Queimadura Solar/patologia , Tiocarbamatos/químicaRESUMO
Plants rich in antioxidant substances may be a promising strategy for preventing UV-induced oxidative and inflammatory damage of the skin. Pimenta pseudocaryophyllus is native to Brazil and presents flavonoids and other polyphenolic compounds in high concentration. Thus, the present study evaluated the possible effects of topical formulations containing P. pseudocaryophyllus ethanolic extract (PPE) at inhibiting UV-B irradiation-induced oxidative stress and inflammation. PPE was administered on the dorsal skin of hairless mice using two formulations: F1 (non-ionic emulsion with high lipid content) and F2 (anionic emulsion with low lipid content) before and after UV-B irradiation. The following parameters were evaluated in skin samples: edema, myeloperoxidase activity, cytokines levels, matrix metalloprotease-9 (MMP-9) secretion/activity, reduced glutathione (GSH), superoxide anion and lipid peroxidation levels, and mRNA expression for glutathione reductase and gp91phox. The UV-B irradiation increased all parameters, except for IL-10 levels and glutathione reductase mRNA expression, which were not altered, and GSH levels, which were reduced by exposure to UV-B light. Treatments with F1 and F2 containing PPE inhibited UV-B-induced edema formation (89% and 86%), myeloperoxidase activity (85% and 81%), IL-1ß production (62% and 82%), MMP-9 activity (71% and 74%), GSH depletion (73% and 85%), superoxide anion (83% and 66%) and TBARS (100% and 100%) levels, increased glutathione reductase (2.54 and 2.55-fold) and reduced gp91phox (67% and 100%) mRNA expression, respectively. F2 containing PPE also increased IL-10 levels. Therefore, this study demonstrates the effectiveness of topical formulations containing PPE in inhibiting UV-B irradiation-induced inflammation and oxidative stress of the skin.
Assuntos
Estresse Oxidativo/efeitos dos fármacos , Pimenta/química , Extratos Vegetais/farmacologia , Raios Ultravioleta/efeitos adversos , Administração Tópica , Animais , Química Farmacêutica , Citocinas/metabolismo , Edema/etiologia , Edema/prevenção & controle , Etanol/química , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos da radiação , Glutationa Redutase/genética , Inflamação/etiologia , Inflamação/prevenção & controle , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Glicoproteínas de Membrana/genética , Camundongos , Camundongos Pelados , NADPH Oxidase 2 , NADPH Oxidases/genética , Estresse Oxidativo/efeitos da radiação , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Pele/efeitos dos fármacos , Pele/metabolismoRESUMO
Solar ultraviolet (UV) radiation, particularly its UVB (280-320 nm) spectrum, is the primary environmental stimulus leading to skin carcinogenesis. Several botanical species with antioxidant properties have shown photochemopreventive effects against UVB damage. Costa Rica's tropical highland blackberry (Rubus adenotrichos) contains important levels of phenolic compounds, mainly ellagitannins and anthocyanins, with strong antioxidant properties. In this study, we examined the photochemopreventive effect of R. adenotrichos blackberry juice (BBJ) on UVB-mediated responses in human epidermal keratinocytes and in a three-dimensional (3D) reconstituted normal human skin equivalent (SE). Pretreatment (2 h) and posttreatment (24 h) of normal human epidermal keratinocytes (NHEKs) with BBJ reduced UVB (25 mJ cm(-2))-mediated (1) cyclobutane pyrimidine dimers (CPDs) and (2) 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) formation. Furthermore, treatment of NHEKs with BBJ increased UVB-mediated (1) poly(ADP-ribose) polymerase cleavage and (2) activation of caspases 3, 8 and 9. Thus, BBJ seems to alleviate UVB-induced effects by reducing DNA damage and increasing apoptosis of damaged cells. To establish the in vivo significance of these findings to human skin, immunohistochemistry studies were performed in a 3D SE model, where BBJ was also found to decrease CPDs formation. These data suggest that BBJ may be developed as an agent to ameliorate UV-induced skin damage.