RESUMO
Surfacen® is a clinical surfactant preparation of porcine origin. In the present study, we have evaluated the effect of Surfacen® in the modulation of oxidative burst in monocytes and neutrophils in human blood and pro-inflammatory cytokine production in peripheral blood mononuclear cells (PBMC). Reactive oxygen species (ROS) level was measured in monocytes and neutrophils by flow cytometry using 2,7-dichlorofluorescein diacetate (DCFH-DA) as substrate, while, tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels were estimated in PBMC supernatant by enzyme-linked immunosorbent assays (ELISA). Our results show that Staphylococcus aureus-induced ROS level was slightly affected by Surfacen® added to whole blood monocytes and neutrophils. The time course experiments of pre-incubation with Surfacen® showed no significant increase of ROS level at 2h; however, the ROS level decreased when pre incubated for 4h and 6h with Surfacen®. Pre-incubation of PBMC cells with Surfacen® at 0.125 and 0.5mg/mL showed a dose-dependent suppression of TNF-α levels measured after 4h of S. aureus stimulation, an effect less impressive when cells were stimulated for 24h. A similar behavior was observed in IL-6 release. In summary, the present study provides experimental evidence supporting an anti-inflammatory role of Surfacen® in human monocytes and neutrophils in vitro.
Assuntos
Citocinas/imunologia , Inflamação/tratamento farmacológico , Monócitos/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Espécies Reativas de Oxigênio/imunologia , Staphylococcus aureus/imunologia , Tensoativos/farmacologia , Adulto , Animais , Feminino , Humanos , Inflamação/imunologia , Interleucina-6/imunologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Masculino , Monócitos/imunologia , Neutrófilos/imunologia , Fosfolipídeos/imunologia , Fosfolipídeos/farmacologia , Proteínas Associadas a Surfactantes Pulmonares/imunologia , Proteínas Associadas a Surfactantes Pulmonares/farmacologia , Explosão Respiratória/efeitos dos fármacos , Explosão Respiratória/imunologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/imunologia , Suínos , Fator de Necrose Tumoral alfa/imunologiaRESUMO
SURFACEN(®) is a biological product produced from pig lungs. Since these animals can be potential sources of microbial pathogens such as viruses, the manufacturing process of this product should guarantee safety from health hazards. The SURFACEN(®) production procedure is capable of effective viral clearance (inactivation/removal) by involving two stages of organic solvent extraction followed by acetone precipitation and heat treatment. In this study, we evaluated the clearance capacity of these four stages for a wide range of viruses by performing spiking experiments. Residual contamination was assessed using a Tissue Culture Infectious Dose assay (log10 TCID50). The validation study demonstrated that, for all viruses tested, the TCID50 titers were reduced by more than 2 log10 in each stage. Total log reduction values achieved were between ≥17.82 log10 and ≥27.93 log10, depending on the virus physical properties, titer, and the number of processing stages applied. Results indicated that the production procedure of SURFACEN(®) can inactivate or remove contaminant viruses from the raw material.
Assuntos
Desinfecção/métodos , Fosfolipídeos/farmacologia , Proteínas Associadas a Surfactantes Pulmonares/farmacologia , Inativação de Vírus/efeitos dos fármacos , Vírus , Animais , Bovinos , Humanos , Pulmão/química , Fosfolipídeos/química , Proteínas Associadas a Surfactantes Pulmonares/química , SuínosRESUMO
Leishmaniasis is caused by a parasite of the Leishmania genus, affecting more than 12 million people in 98 countries. The control of leishmaniasis remains a serious problem. There are currently no vaccines for leishmaniasis. The drugs available are toxic, expensive and frequently ineffective. The in vitro activity of SURFACEN® and SP-A against Leishmania amazonensis was evaluated. The combination of both products resulted in a synergic pharmacology effect, demonstrated by a fractional inhibitory concentration index <0.5. A more effective combination was a SURFACEN/SP-A ratio of 4:1, using a method of fixed ratio. The therapeutic effect of SURFACEN and SP-A as antileishmanial compounds was demonstrated, with a potentiation of activity when they were incubated in conjunction. Our results propose an exploration of these products in order to design new formulations against the Leishmania parasite.
Assuntos
Leishmania/efeitos dos fármacos , Fosfolipídeos/farmacologia , Proteína A Associada a Surfactante Pulmonar/farmacologia , Proteínas Associadas a Surfactantes Pulmonares/farmacologia , Animais , Antiparasitários/farmacologia , Sinergismo Farmacológico , Leishmania/isolamento & purificação , Macrófagos/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , SuínosRESUMO
Surfacen® is an exogenous natural lung surfactant, composed by phospholipids and hydrophobic proteins, which is applied successfully in Newborn Respiratory Distress Syndrome. In this paper, in vitro activity of Surfacen® against Leishmania amazonensis is described. The product showed activity against the amastigote form found in peritoneal macrophages from BALB/c mice, with an IC50 value of 17.9 ± 3.0 µg/mL; while no toxic effect on host cell was observed up to 200 µg/mL. This is the first report about the antileishmanial activity of Surfacen®.
Assuntos
Antiprotozoários/farmacologia , Leishmania mexicana/efeitos dos fármacos , Fosfolipídeos/farmacologia , Proteínas Associadas a Surfactantes Pulmonares/farmacologia , Animais , Dose Letal Mediana , Macrófagos Peritoneais/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Parasitária , Surfactantes Pulmonares/farmacologiaRESUMO
Surfacen® is an exogenous natural lung surfactant, composed by phospholipids and hydrophobic proteins, which is applied successfully in Newborn Respiratory Distress Syndrome. In this paper, in vitro activity of Surfacen® against Leishmania amazonensis is described. The product showed activity against the amastigote form found in peritoneal macrophages from BALB/c mice, with an IC50 value of 17.9 ± 3.0 µg/mL; while no toxic effect on host cell was observed up to 200 µg/mL. This is the first report about the antileishmanial activity of Surfacen®.
Surfacen® es un surfactante natural exógeno extraído del pulmón, formado por fosfolípidos y proteínas hidrofóbicas, el cual es aplicado con éxito en el Síndrome de Distrés Respiratorio en Niños Recién Nacidos. En este trabajo, se describe la actividad in vitro del Surfacen® contra Leishmania amazonensis. El producto mostró actividad frente a amastigotes que se encuentran en macrófagos peritoneales de ratón BALB/c, con una CI50 de 17.9 ± 3.0 µg/mL, mientras no se observaron efectos tóxicos sobre la célula hospedera hasta 200 µg/mL. Este estudio constituye el primer reporte sobre la actividad antileishmania del Surfacen®.