RESUMO
Ultraviolet radiation is an environmental carcinogenic agent that enhances inflammation and immunological reactions in the exposed human skin cells leading to oxidative photoaging of the epidermal and dermal segment. In the present study, we investigated the protective role of ursolic acid (UA) against ultraviolet B (UVB) radiation- induced photoaging an in vitro model of human skin dermal fibroblasts. UA-pretreated human skin dermal fibroblast (HDF) cells were exposed to UVB radiation to evaluated cell viability, reactive oxygen species (ROS), mitochondrial membrane potential, lipid peroxidation, antioxidant status, DNA damage, proinflammatory response, apoptotic induction, and matrix metalloproteinase (MMP) alteration. The UA pretreatment of HDFs mitigated the UVB irradiation-induced cytotoxicity, ROS generation, and mitochondrial membrane potential alteration and lipid peroxidation, depletion of antioxidant status, DNA damage, and apoptotic induction. UA pretreatment of HDFs also attenuated the UVB-induced expression of inflammatory (TNF-α and NF-κB) and apoptotic (p53, Bax, and caspase-3) and MMPs (MMP-2 and MMP-9) and enhanced the Bcl-2 protein levels in 20 µM UA treatment, when compared to concentrations. Hence, these results revealed that UA has the potential to mitigate UVB-induced extracellular damage by interfering with the ROS-mediated apoptotic induction and photoaging senescence and thus is a potential therapeutic agent to protect the skin against UVB-irradiation induced photooxidative damage.
Assuntos
Senescência Celular , Derme/patologia , Fibroblastos/patologia , Inflamação/patologia , Estresse Oxidativo/efeitos dos fármacos , Triterpenos/farmacologia , Raios Ultravioleta , Caspase 3/metabolismo , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Núcleo Celular/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Senescência Celular/efeitos da radiação , Dano ao DNA , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos da radiação , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Triterpenos/química , Fator de Necrose Tumoral alfa/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/metabolismo , Ácido UrsólicoRESUMO
The present study, we investigate the preventive role of naringin, a dietary flavonoid, against ultraviolet-B (UVB) radiation (280-320 nm) induced oxidative damage and inflammatory responses in mouse embryonic fibroblast cell lines (NIH-3T3). In this study, 20 mJ/cm 2 of UVB radiation induces cell cytotoxicity, reactive oxygen species (ROS) generation, DNA damage, and antioxidants depletion in NIH-3T3 cells. Treatment with naringin (60 µM) prior UVB exposure prevented the cell cytotoxicity, ROS generation, DNA damage, and antioxidants depletion in NIH-3T3 cells. Furthermore, naringin prevents UVB-induced mitogen-activated protein kinase families and nuclear factor-κB (NF-κB)-mediated activation of inflammatory factors, that is TNF-α, IL-6, IL-10, and COX-2 in NIH-3T3 cells. Peroxisome proliferator-activated receptor γ (PPARγ) is an anti-inflammatory agent and it suppressed the UVB-mediated oxidative and inflammatory responses. In this study, naringin activates PPARγ and prevents inflammatory biomarkers in NIH-3T3 cells. Thus, naringin prevents UVB-mediated inflammation and oxidative damage in NIH-3T3 cells probably over controlling NF-κB expression and activation of PPARγ.
Assuntos
Flavanonas/farmacologia , Inflamação/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , PPAR gama/metabolismo , Raios Ultravioleta , Animais , Anti-Inflamatórios/farmacologia , Dano ao DNA , Camundongos , NF-kappa B/metabolismo , Células NIH 3T3 , Estresse Oxidativo/efeitos da radiação , Transdução de SinaisRESUMO
We investigated the effect of apigenin, a dietary flavonoid, on isoproterenol hydrochloride (ISO)-induced apoptotic signaling in cardiomyoblast H9C2 cells. The results showed that apigenin treatment (10 µM) prevented ISO (31.25 µM)-induced lipid peroxidative levels and antioxidants status in H9C2 cells. Furthermore, apigenin inhibited expression of inflammatory markers in ISO-treated cells. In addition, apigenin prevented ISO-induced DNA damage and apoptotic signaling through modulating the expression of Bax, caspase-3, -8 and -9, cytochrome c, and Fas proteins in H9C2 cells. It is concluded that apigenin prevents ISO-induced antioxidants depletion, oxidative DNA damage, inflammatory, and apoptotic signaling in H9C2 cells. Thus, the present results demonstrated that apigenin has a cardioprotective effect on cardiomyoblasts cells.
Assuntos
Antioxidantes/farmacologia , Apigenina/farmacologia , Apoptose/efeitos dos fármacos , Cardiotônicos/efeitos adversos , Isoproterenol/efeitos adversos , Mioblastos Cardíacos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Biomarcadores/metabolismo , Cardiotônicos/antagonistas & inibidores , Linhagem Celular , Dano ao DNA/efeitos dos fármacos , Mediadores da Inflamação/agonistas , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Isoproterenol/antagonistas & inibidores , Peroxidação de Lipídeos/efeitos dos fármacos , Potencial da Membrana Mitocondrial , Mitocôndrias Cardíacas/efeitos dos fármacos , Mitocôndrias Cardíacas/imunologia , Mitocôndrias Cardíacas/metabolismo , Membranas Mitocondriais/efeitos dos fármacos , Membranas Mitocondriais/imunologia , Membranas Mitocondriais/metabolismo , Mioblastos Cardíacos/citologia , Mioblastos Cardíacos/imunologia , Mioblastos Cardíacos/metabolismo , Ratos , Proteína X Associada a bcl-2/agonistas , Proteína X Associada a bcl-2/antagonistas & inibidores , Proteína X Associada a bcl-2/metabolismo , Receptor fas/agonistas , Receptor fas/antagonistas & inibidores , Receptor fas/metabolismoRESUMO
Previously, we proved that caffeic acid (CA), a major dietary phenolic acid, prevents skin carcinogenesis by modulating inflammatory signaling in mouse skin. However, the actual mechanisms of CA against UVB (280-320â¯nm) induced photocarcinogenesis remains unclear. The present results confirms that CA significantly inhibits single UVB-induced CPDs formation, oxidative DNA damage, ROS generation and frequency of apoptotic cell death in human dermal fibroblasts (HDFa). Furthermore, CA prevents UVB-induced expression of PI3K and AKT kinases through activation of PTEN which subsequently promotes XPC dependant NER proteins such as XPC, XPE, TFIIH (p44) and ERCC1 in HDFa cells and mouse skin tissue. Further, CA directly activates PTEN through hydrogen bond and hydrophobic interactions. Taken together, these findings suggest that CA prevents UVB-induced photodamage through the activation of PTEN expression in human dermal fibroblasts and mouse skin.