RESUMO
AIM: To evaluate the cytotoxicity and the mechanism of cell aggression of peracetic acid (PA) in comparison with sodium hypochlorite (NaOCl). METHODOLOGY: L929 fibroblasts were exposed to 1% PA and 2.5% NaOCl, at several dilutions for 10 min. The following parameters were evaluated: cell metabolism by methylthiazol tetrazolium assay, external morphology by scanning electron microscopy, ultrastructure by transmission electron microscopy, the cytoskeleton by means of actin and α-tubulin labelling, and the type of cell death by flow cytometry (apoptosis/necrosis). The data were analysed by two-way anova and the Bonferroni post-test (α = 0.05). RESULTS: The PA group had lower cell viability and a higher percentage of necrotic cells than the NaOCl group (P < 0.05). Both solutions diminished cell metabolism, led to destructuring of the cytoskeleton, created changes in the external morphology, resulted in the accumulation of proteins in the rough endoplasmic reticulum and induced cell death predominantly by necrosis. However, these changes were observed in lower doses of PA when compared with NaOCl. CONCLUSIONS: Although they had the same mechanism of cytotoxicity, 1% PA had greater cytotoxic potential than 2.5% NaOCl.
Assuntos
Apoptose/efeitos dos fármacos , Desinfetantes/toxicidade , Fibroblastos/efeitos dos fármacos , Ácido Peracético/toxicidade , Animais , Técnicas de Cultura de Células , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citoesqueleto/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/ultraestrutura , Citometria de Fluxo , Camundongos , Microscopia Eletrônica , Necrose , Hipoclorito de Sódio/toxicidadeRESUMO
Garlic (Allium sativum L.) is grown all over the world as seasoning and medicinal vegetable since 3,000 BC. Allicin is the main component of garlic, being attributed to it the most of its biological activities, such as bactericidal, antifungal and antiviral actions. However, other compounds of garlic present antioxidant, hypocholesterolemic, vasodilator activities, protective action against different types of cancer, and immunomodulatory. Fungal infections are important causes of morbidity and mortality in people mainly in immunosuppressed ones. Sporothrix schenckii, the causing agent of Sporotrichosis (most common subcutaneous mycosis in Latin America), is dimorphic fungus, of saprophytic life in soil or plants, infecting people and animals mainly through skin injuries and bruises. The main of this work was to evaluate the influence of garlic consuming on immune modulation of healthy and infected Swiss mice in induced way by S. schenckii, since these animals functioning of peritoneal macrophages as well as the nitric oxide and cytokines production (IL-1β, IL-10 and IL-12) and to evaluate the antifungal potential of garlic with S. schenckii through minimum inhibitory concentration test and colony-forming units. The results showed that garlic offers antifungal potential with S. schenckii. The oral taking of garlic extracts influences the releasing of cytokines by macrophages, regular consuming shows anti-inflammatory effect, and its acute use may take to an inflammatory response. Mice that consumed garlic responded more effectively to fight against the infection.(AU)
O alho (Allium sativum L.) é cultivado em todo o mundo como hortaliça condimentar e medicinal desde 3.000 a. C. A alicina é o principal componente do alho, sendo atribuída a ela a maior parte das suas atividades biológicas, dentre elas as ações bactericida, antifúngica e antiviral. Porém, outros compostos do alho apresentam atividade antioxidante, hipocolesterolemiante, vasodilatadora, ação protetora contra diversos tipos de câncer e imunomoduladora. As infecções por fungos são causas importantes de morbidade e mortalidade no homem principalmente em indivíduos imunossuprimidos. O Sporothrix schenckii, agente causal da esporotricose (micose subcutânea mais comum na América Latina), é fungo dimórfico, de vida saprofítica no solo ou em vegetais, infectando homens e os animais principalmente através de lesões e arranhões na pele. O objetivo desse trabalho foi avaliar a influência do consumo de alho na imunomodulação de camundongos Swiss saudáveis e infectados de forma induzida por S. schenckii, a partir do estado funcional dos macrófagos peritoneais desses animais quanto à produção de óxido nítrico e das citocinas (IL-1β, IL-10 and IL-12) e avaliar o potencial antifúngico do alho frente ao S. schenckii por meio de teste de concentração inibitória mínima e unidades formadoras de colônia. Os resultados demonstraram que o alho apresenta potencial antifúngico frente S. schenckii. A administração oral de extratos de alho influencia a liberação de citocinas por macrófagos, o consumo regular apresenta efeito anti-inflamatório, e seu uso agudo pode gerar uma resposta inflamatória. Camundongos que consumiram alho responderam de forma mais efetiva no combate da infecção.(AU)
Assuntos
Animais , Masculino , Adulto , Camundongos , Alho , Esporotricose/terapia , Imunomodulação , Macrófagos Peritoneais/imunologia , Modelos Animais de DoençasRESUMO
Abstract Garlic (Allium sativum L.) is grown all over the world as seasoning and medicinal vegetable since 3,000 BC. Allicin is the main component of garlic, being attributed to it the most of its biological activities, such as bactericidal, antifungal and antiviral actions. However, other compounds of garlic present antioxidant, hypocholesterolemic, vasodilator activities, protective action against different types of cancer, and immunomodulatory. Fungal infections are important causes of morbidity and mortality in people mainly in immunosuppressed ones. Sporothrix schenckii, the causing agent of Sporotrichosis (most common subcutaneous mycosis in Latin America), is dimorphic fungus, of saprophytic life in soil or plants, infecting people and animals mainly through skin injuries and bruises. The main of this work was to evaluate the influence of garlic consuming on immune modulation of healthy and infected Swiss mice in induced way by S. schenckii, since these animals functioning of peritoneal macrophages as well as the nitric oxide and cytokines' production (IL-1β, IL-10 and IL-12) and to evaluate the antifungal potential of garlic with S. schenckii through minimum inhibitory concentration test and colony-forming units. The results showed that garlic offers antifungal potential with S. schenckii. The oral taking of garlic extracts influences the releasing of cytokines by macrophages, regular consuming shows anti-inflammatory effect, and its acute use may take to an inflammatory response. Mice that consumed garlic responded more effectively to fight against the infection.
Resumo O alho (Allium sativum L.) é cultivado em todo o mundo como hortaliça condimentar e medicinal desde 3.000 a. C. A alicina é o principal componente do alho, sendo atribuída a ela a maior parte das suas atividades biológicas, dentre elas as ações bactericida, antifúngica e antiviral. Porém, outros compostos do alho apresentam atividade antioxidante, hipocolesterolemiante, vasodilatadora, ação protetora contra diversos tipos de câncer e imunomoduladora. As infecções por fungos são causas importantes de morbidade e mortalidade no homem principalmente em indivíduos imunossuprimidos. O Sporothrix schenckii, agente causal da esporotricose (micose subcutânea mais comum na América Latina), é fungo dimórfico, de vida saprofítica no solo ou em vegetais, infectando homens e os animais principalmente através de lesões e arranhões na pele. O objetivo desse trabalho foi avaliar a influência do consumo de alho na imunomodulação de camundongos Swiss saudáveis e infectados de forma induzida por S. schenckii, a partir do estado funcional dos macrófagos peritoneais desses animais quanto à produção de óxido nítrico e das citocinas (IL-1β, IL-10 e IL-12) e avaliar o potencial antifúngico do alho frente ao S. schenckii por meio de teste de concentração inibitória mínima e unidades formadoras de colônia. Os resultados demonstraram que o alho apresenta potencial antifúngico frente S. schenckii. A administração oral de extratos de alho influencia a liberação de citocinas por macrófagos, o consumo regular apresenta efeito anti-inflamatório, e seu uso agudo pode gerar uma resposta inflamatória. Camundongos que consumiram alho responderam de forma mais efetiva no combate da infecção.
Assuntos
Animais , Masculino , Camundongos , Esporotricose/tratamento farmacológico , Sporothrix/efeitos dos fármacos , Extratos Vegetais/farmacologia , Macrófagos Peritoneais/imunologia , Alho/química , Antifúngicos/farmacologia , Citocinas/metabolismo , Macrófagos Peritoneais/efeitos dos fármacos , ImunomodulaçãoRESUMO
Garlic (Allium sativum L.) is grown all over the world as seasoning and medicinal vegetable since 3,000 BC. Allicin is the main component of garlic, being attributed to it the most of its biological activities, such as bactericidal, antifungal and antiviral actions. However, other compounds of garlic present antioxidant, hypocholesterolemic, vasodilator activities, protective action against different types of cancer, and immunomodulatory. Fungal infections are important causes of morbidity and mortality in people mainly in immunosuppressed ones. Sporothrix schenckii, the causing agent of Sporotrichosis (most common subcutaneous mycosis in Latin America), is dimorphic fungus, of saprophytic life in soil or plants, infecting people and animals mainly through skin injuries and bruises. The main of this work was to evaluate the influence of garlic consuming on immune modulation of healthy and infected Swiss mice in induced way by S. schenckii, since these animals functioning of peritoneal macrophages as well as the nitric oxide and cytokines' production (IL-1ß, IL-10 and IL-12) and to evaluate the antifungal potential of garlic with S. schenckii through minimum inhibitory concentration test and colony-forming units. The results showed that garlic offers antifungal potential with S. schenckii. The oral taking of garlic extracts influences the releasing of cytokines by macrophages, regular consuming shows anti-inflammatory effect, and its acute use may take to an inflammatory response. Mice that consumed garlic responded more effectively to fight against the infection.
Assuntos
Antifúngicos/farmacologia , Alho/química , Macrófagos Peritoneais/imunologia , Extratos Vegetais/farmacologia , Sporothrix/efeitos dos fármacos , Esporotricose/tratamento farmacológico , Animais , Citocinas/metabolismo , Imunomodulação , Macrófagos Peritoneais/efeitos dos fármacos , Masculino , CamundongosRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Vismia guianensis (Aubl.) Pers. is traditionally used in North and Northeast of Brazil for the treatment of dermatomycoses. Since the strategy associating immunomodulators with antifungal drugs seems to be promissory to improve the treatment efficacy in fungal infections, we aimed to investigate the antifungal activity of V. guianensis ethanolic extract of leaves (VGL) and bark (VGB) against Sporothrix schenckii ATCC 16345 and their antinflammatory activities. MATERIAL AND METHODS: The extracts were analyzed by HPLC-DAD-IT MS/MS for in situ identification of major compounds. Antifungal activity was evaluated in vitro (microdilution test) and in vivo using a murine model of S. schenckii infection. The production of TNF-α, IFN-γ, IL-4, IL-10 and IL-12 by measured by ELISA, as well as measured the production and inhibition of the NO after treatment with the plant extracts or itraconazole (ITR). RESULTS: Two O-glucosyl-flavonoids and 16 prenylated benzophenone derivatives already described for Vismia were detected. Both VGL and VGB showed significant antifungal activity either in in vitro assay of microdilution (MIC=3.9µg/mL) and in vivo model of infection with reduction of S. schenckii load in spleen. It was also observed a predominance of reduction in the production of NO and the proinflammatory cytokines evaluated except TNFα, but with stimulation of IL-10, as evidence of a potential anti-inflammatory effect associated. CONCLUSION: The results showed that both VGL and VGB have a significant antifungal against S. schenckii and an anti-inflammatory activity. These results can support the use of these extracts for alternative treatment of sporotrichosis.
Assuntos
Anti-Inflamatórios/farmacologia , Antifúngicos/farmacologia , Clusiaceae/química , Extratos Vegetais/farmacologia , Sporothrix/efeitos dos fármacos , Esporotricose/prevenção & controle , Animais , Anti-Inflamatórios/isolamento & purificação , Antifúngicos/isolamento & purificação , Células Cultivadas , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Etanol/química , Interferon gama/metabolismo , Interleucina-10/metabolismo , Interleucina-12/metabolismo , Interleucina-4/metabolismo , Itraconazol/farmacologia , Masculino , Camundongos Endogâmicos BALB C , Óxido Nítrico/metabolismo , Fitoterapia , Casca de Planta/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Plantas Medicinais , Solventes/química , Sporothrix/imunologia , Esporotricose/imunologia , Esporotricose/metabolismo , Esporotricose/microbiologia , Espectrometria de Massas em Tandem , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Sporothrix schenckii is a complex of various species of fungus found in soils, plants, decaying vegetables and other outdoor environments. It is the aetiological agent of sporotrichosis in humans and several animals. Humans and animals can acquire the disease through traumatic inoculation of the fungus into subcutaneous tissue. Despite the importance of sporotrichosis, it being currently regarded as an emergent disease in several countries, the factors driving its increasing medical importance are still largely unknown. There have only been a few studies addressing the influence of the environment on the virulence of these pathogens. However, recent studies have demonstrated that adverse conditions in its natural habitats can trigger the expression of different virulence factors that confer survival advantages both in animal hosts and in the environment. In this review, we provide updates on the important advances in the understanding of the biology of Spor. schenckii and the modification of its virulence linked to demonstrated or putative environmental factors.
Assuntos
Sporothrix/patogenicidade , Esporotricose/microbiologia , Animais , Microbiologia Ambiental , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Humanos , Sporothrix/genética , Sporothrix/fisiologia , VirulênciaRESUMO
Sporotrichosis is a disease caused by the dimorphic fungus Sporothrix schenckii. The main clinical manifestations occur in the skin, however the number of systemic and visceral cases has increased, especially in immunocompromised patients. Dendritic cells (DCs) are highly capable to recognize the fungus associated data and translate it into differential T cells responses both in vivo and in vitro. Although, the mechanisms involved in the interaction between DCs and S. schenckii are not fully elucidated. The present study investigated the phenotypic and functional changes in bone marrow dendritic cells (BMDCs) stimulated in vitro with the yeast form of S. schenckii or exoantigen (ExoAg) and its ability to trigger a cellular immune response in vitro. Our results demonstrated that the live yeast of S. schenckii and its exoantigen, at a higher dose, were able to activate BMDCs and made them capable of triggering T cell responses in vitro. Whereas the yeast group promoted more pronounced IFN-γ production rather than IL-17, the Exo100 group generated similar production of both cytokines. The exoantigen stimulus suggests a capability to deviate the immune response from an effector Th1 to an inflammatory Th17 response. Interestingly, only the Exo100 group promoted the production of IL-6 and a significant increase of TGF-ß, in addition to IL-23 production. Interestingly, only Exo100 group was capable to promote the production of IL-6 and a significant increase on TGF-ß, in addition with IL-23 detection. Our results demonstrated the plasticity of DCs in translating the data associated with the fungus S. schenckii and ExoAg into differential T cell responses in vitro. The possibility of using ex vivo-generated DCs as vaccinal and therapeutic tools for sporotrichosis is a challenge for the future.
Assuntos
Antígenos de Fungos/imunologia , Células Dendríticas/imunologia , Sporothrix/imunologia , Esporotricose/imunologia , Células Th1/imunologia , Células Th17/imunologia , Animais , Células da Medula Óssea/imunologia , Células da Medula Óssea/metabolismo , Antígeno CD11c/imunologia , Antígeno CD11c/metabolismo , Diferenciação Celular/imunologia , Células Cultivadas , Técnicas de Cocultura , Citocinas/imunologia , Citocinas/metabolismo , Células Dendríticas/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Interações Hospedeiro-Patógeno/imunologia , Humanos , Interleucina-23/imunologia , Interleucina-23/metabolismo , Interleucina-6/imunologia , Interleucina-6/metabolismo , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Sporothrix/fisiologia , Esporotricose/metabolismo , Esporotricose/microbiologia , Células Th1/metabolismo , Células Th17/metabolismo , Fator de Crescimento Transformador beta/imunologia , Fator de Crescimento Transformador beta/metabolismoRESUMO
Dois biomarcadores do estresse oxidativo foram avaliados em indivíduos saudáveis que receberam doses diárias de suco de laranja, notadamente uma fonte de vitamina C e de flavanonas, que têm sido associadas aos efeitos antioxidante, anti-inflamatório e hipolipidêmico. A capacidade antioxidante do soro sanguíneo foi avaliada através da redução do radical 2,2-difenil-1-picril-hidrazila (DPPH) e a peroxidação lipídica foi avaliada pela presença de substâncias reativas ao ácido tiobarbitúrico (TBARS). Os resultados mostraram que após o período de suplementação com o suco de laranja houve um aumento 150% na capacidade antioxidante no soro das mulheres e 200% no soro dos homens (p<0,001), mas não houve alteração na peroxidação lipídica no sangue dos voluntários. Concluindo, o aumento das reservas de flavanonas e de vitamina C, decorrente da ingestão regular de suco de laranja, melhorou expressivamente a capacidade antioxidante no sangue, sem, entretanto, apresentar efeito sobre a peroxidação lipídica.
Two biomarkers of oxidative stress were evaluated in healthy volunteers treated with daily doses of orange juice that is well known source of vitamin C and citric flavanones, which have been associated with antioxidant, anti-inflammatory and hypolipidemic effects. The antioxidant capacity in the blood serum was evaluated by studying the scavenging of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical, and also lipid peroxidation was evaluated by the thiobarbituric acid reacting substances (TBARS) assay. The results have shown that the regular consumption of orange juice increased 150% and 200% the serum antioxidant capacity for women and men respectively, but it was no significant change in the serum lipid peroxidation. In conclusion, the increase of flavonones and vitamin C in the body due to the regular intake of orange juice expressively improved the antioxidant capacity, but without significant effect on the lipid peroxidation.
Assuntos
Humanos , Ácido Ascórbico/sangue , Bebidas Gaseificadas , Citrus sinensis , Flavonas/sangue , Peroxidação de Lipídeos , Estresse OxidativoRESUMO
Complexes of the type [PdX2(tdmPz)] {X=Cl-(1), Br-(2); I-(3); SCN-(4); tdmPz=1-thiocarbamoyl-3,5-dimethylpyrazole} have been synthesized and characterized. Compound 1 was formed from the reaction between [PdCl2(CH3CN)2] and 1-thiocarbamoyl-3,5-dimethylpyrazole. Complexes 2, 3 and 4 were obtained by metathesis of the chloro groups from 1 by bromide, iodide and thiocyanate ions, respectively. All the compounds and cisplatin have been tested in vitro by MTT assay for their cytotoxicity against three murine cancer cell lines: mammary adenocarcinoma (LM3 and LMM3) and lung adenocarcinoma (LP07) as well towards normal murine peritoneal exudate cells (PEC). Promising cytotoxic effect against LM3 has been found for 3 showing IC50 equal to 24.5 microM which is comparable to the value obtained for cisplatin (30.3 microM).