RESUMEN

Air particulate matter has been associated with adverse effects in the cardiorespiratory system leading to cytotoxic and pro-inflammatory effects. Particulate matter-associated cardiac effects may be direct or indirect. While direct interactions may occur when inhaled ultrafine particles and/or particle components cross the air-blood barrier reaching the cardiac tissue, indirect interactions may occur as the result of pulmonary inflammation and consequently the release of inflammatory and oxidative mediators into the blood circulation. The aim of the study is to investigate the direct or indirectly the effect of Urban Air particles from downtown Buenos Aires (UAP-BA) and residual oil fly ash (ROFA), a surrogate of ambient air pollution, on cardiomyocytes (HL-1 cells). HL-1 cultured cells were directly exposed to particulate matter [UAP-BA (10-200 µg/ml), ROFA (1-100 µg/ml)] or indirectly exposed to conditioned media (CM) from particle-exposed alveolar macrophages (AM). Metabolic activity, reactive oxygen species (ROS), and Nrf2 expression were assessed by MTT, DHR 123, and immunocytochemistry techniques, respectively. We found that direct exposure of cardiomyocytes to UAP-BA or ROFA increased ROS generation but the oxidative damage did not alter metabolic activity likely by a concomitant increase in the cytoplasmic and nuclear Nrf2 expression. However, indirect exposure through CM caused a marked reduction on cardiac metabolic activity probably due to the rise in ROS generation without Nrf2 translocation into the cell nuclei. In this in vitro model, our results indicate both direct and indirect PM effects on cardiomyocytes cells in culture. Our findings employing lung and cardiomyocytes cells provide support to the hypothesis that particle-induced cardiac alteration may possibly involve lung-derived mediators.

Asunto(s)

Contaminantes Atmosféricos/toxicidad , Miocitos Cardíacos/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , Material Particulado/toxicidad , Animales , Argentina , Línea Celular , Medios de Cultivo Condicionados/metabolismo , Macrófagos Alveolares/efectos de los fármacos , Macrófagos Alveolares/metabolismo , Masculino , Ratones Endogámicos BALB C , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Estrés Oxidativo/efectos de los fármacos , Comunicación Paracrina/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal

RESUMEN

Epidemiological studies have associated air particulate matter (PM) inhalation with a decline in lung function and increased morbo-mortality due to cardiorespiratory diseases, particularly in susceptible populations. Sjögren's Syndrome (SS) is a chronic autoimmune disease characterized by cellular infiltration in exocrine glands and extraglandular tissue, being the respiratory tract an important target. We evaluated the effect of PM on the airways of NOD mice, which develop SS and BALB/c mice. BALB/c or NOD mice (2-3 months) were randomized in two groups and exposed to intranasal instillation either with saline (control) or ROFA solution (1mg/kg body weight). After 24h, mice were euthanized in order to perform lung histology, or measure total cell number (TCN), differential cell count (DCC) and superoxide anion generation in the bronchoalveolar lavage (BAL) fluid. BALB/c mice showed normal histoarchitecture, while NOD mice showed lymphocytic peribronchial infiltrates. ROFA exposure affected the respiratory tract from both BALB/c and NOD mice, with a significant increase in the TCN (p<0.05) and generation of O2(-) (p<0.05), as well as an imbalance in the DCC (p<0.05). All histological observations correlated with the cellular parameters evaluated. Lesions in NOD mice were more severe than those of BALB/c, showing cellular infiltration in the alveoli and leading to a greater decrease in the alveolar space. We have proved that in this experimental Sjögren's Syndrome animal model (NOD mice); airborne pollution exacerbates pre-existing pulmonary lesions. These findings show experimental evidence on the harmful effects of airborne pollution on the airways of patients with Sjögren's Syndrome.

Asunto(s)

Contaminantes Atmosféricos/toxicidad , Pulmón/efectos de los fármacos , Material Particulado/toxicidad , Síndrome de Sjögren/inducido químicamente , Animales , Diferenciación Celular , Modelos Animales de Enfermedad , Exposición por Inhalación , Pulmón/patología , Masculino , Ratones Endogámicos BALB C , Ratones Endogámicos NOD , Síndrome de Sjögren/patología

RESUMEN

Air particulate matter has been associated with adverse impact on the respiratory system leading to cytotoxic and proinflammatory effects. The biological mechanisms behind these associations may be initiated by inhaled small size particles, particle components (soluble fraction) and/or mediators released by particle-exposed cells (conditioned media). The effect of Urban Air Particles from Buenos Aires (UAP-BA) and Residual Oil Fly Ash (ROFA) a surrogate of ambient air pollution, their Soluble Fractions (SF) and Conditioned Media (CM) on A549 lung epithelial cells was examined. After 24 h exposure to TP (10 and 100 µg/ml), SF or CM, several biological parameters were assayed on cultured A549 cells. We tested cell viability by MTT, superoxide anion (O2(-)) generation by NBT and proinflammatory cytokine (TNFα, IL-6 and IL-8) production by ELISA. UAP-BA particles or its SF (direct effect) did not modify cell viability and generation of O2(-) for any of the doses tested. On the contrary, UAP-BA CM (indirect effect) reduced cell viability and increased both generation of O2(-) and IL-8 production. Exposure to ROFA particles, SF or ROFA CM reduced proliferation and O2(-) but, stimulated IL-8. It is worth to note that UAP-BA and ROFA depicted distinct effects on particle-exposed A549 cells implicating morphochemical dependence. These in vitro findings support the hypothesis that particle-induced lung inflammation and disease may involve lung-derived mediators.

Asunto(s)

Contaminantes Atmosféricos/toxicidad , Células Epiteliales/efectos de los fármacos , Material Particulado/toxicidad , Alveolos Pulmonares/citología , Argentina , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Ciudades , Medios de Cultivo Condicionados/toxicidad , Citocinas/metabolismo , Células Epiteliales/metabolismo , Humanos , Superóxidos/metabolismo

RESUMEN

Epidemiological studies have shown that air particulate matter (PM) can increase respiratory morbidity and mortality being the lungs the main target organ to PM body entrance. Even more, several in vivo and in vitro studies have shown that air PM has a wide toxicity spectra depending among other parameters, on its size, morphology, and chemical composition. The Reconquista River is the second most polluted river from Buenos Aires, and people living around its basin are constantly exposed to its contaminated water, soil and air. However, the air PM from the Reconquista River (RR-PMa) has not been characterized, and its biological impact on lung has yet not been assessed. Therefore, the present investigation was undertaken to study (1) RR-PMa morphochemical characteristic and (2) RR-PMa lung acute effects after intranasal instillation exposure through the analysis of three end points: oxidative stress, inflammation, and apoptosis. A single acute exposure of RR-PMa (1 mg/kg body weight) after 24 h caused significant (p < 0.05) enrichment in bronchoalveolar total cell number and polymorphonuclear (PNM) fraction, superoxide anion generation, production of pro-inflammatory cytokines TNF-α and IL-6, and induction of apoptosis. It was also observed that in lung homogenates, none of the antioxidant enzymes assayed showed differences between exposed RR-PMa and control mice. These data demonstrate that air PM from the Reconquista River induce lung oxidative stress, inflammation, and cell death therefore represents a potential hazard to human health.

Asunto(s)

Contaminantes Atmosféricos/toxicidad , Material Particulado/toxicidad , Neumonía/inducido químicamente , Animales , Argentina , Muerte Celular , Monitoreo del Ambiente , Masculino , Ratones

RESUMEN

Uranium compounds are widely used in the nuclear fuel cycle, military and many other diverse industrial processes. Health risks associated with uranium exposure include nephrotoxicity, cancer, respiratory, and immune disorders. Macrophages present in body tissues are the main cell type involved in the internalization of uranium particles. To better understand the pathological effects associated with depleted uranium (DU) inhalation, we examined the metabolic activity, phagocytosis, genotoxicity and inflammation on DU-exposed rat alveolar macrophages (12.5-200 µM). Stability and dissolution of DU could differ depending on the dissolvent and in turn alter its biological action. We dissolved DU in sodium bicarbonate (NaHCO3 100 mM) and in what we consider a more physiological vehicle resembling human internal media: sodium chloride (NaCl 0.9%). We demonstrate that uranyl nitrate in NaCl solubilizes, enters the cell, and elicits its cytotoxic effect similarly to when it is diluted in NaHCO3. We show that irrespective of the dissolvent employed, uranyl nitrate impairs cell metabolism, and at low doses induces both phagocytosis and generation of superoxide anion (O2⁻). At high doses it provokes the secretion of TNFα and through all the range of doses tested, apoptosis. We herein suggest that at DU low doses O2⁻ may act as the principal mediator of DNA damage while at higher doses the signaling pathway mediated by O2⁻ may be blocked, prevailing damage to DNA by the TNFα route. The study of macrophage functions after uranyl nitrate treatment could provide insights into the pathophysiology of uranium-related diseases.

Asunto(s)

Mediadores de Inflamación/fisiología , Macrófagos Alveolares/efectos de los fármacos , Superóxidos/metabolismo , Factor de Necrosis Tumoral alfa/fisiología , Nitrato de Uranilo/toxicidad , Animales , Apoptosis , Compuestos Azo , Caspasa 3/metabolismo , Muerte Celular/efectos de los fármacos , Núcleo Celular/efectos de los fármacos , Núcleo Celular/ultraestructura , Células Cultivadas , Colorantes , Inmunohistoquímica , Macrófagos Alveolares/metabolismo , Masculino , Fagocitosis/efectos de los fármacos , Poli(ADP-Ribosa) Polimerasas/metabolismo , Ratas , Ratas Wistar , Transducción de Señal/efectos de los fármacos , Sales de Tetrazolio , Tiazoles

RESUMEN

Exposure to uranium is an occupational hazard to workers who continually handle uranium and an environmental risk to the population at large. Since the cellular and molecular pathways of uranium toxicity in osteoblast cells are still unknown, the aim of the present work was to evaluate the adverse effects of uranyl nitrate (UN) on osteoblasts both in vivo and in vitro. Herein we studied the osteoblastic ultrastructural changes induced by UN in vivo and analyzed cell proliferation, generation of reactive oxygen species (ROS), apoptosis, and alkaline phosphatase (APh) activity in osteoblasts exposed to various UN concentrations (0.1, 1, 10, and 100 microM) in vitro. Cell proliferation was quantified by means of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, ROS was determined using the nitro blue tetrazolium test, apoptosis was morphologically determined using Hoechst 3332 and APh activity was assayed spectrophotometrically. Electron microscopy revealed that the ultrastructure of active and inactive osteoblasts exposed to uranium presented cytoplasmic and nuclear alterations. In vitro, 1-100 microM UN failed to modify cell proliferation ratio and to induce apoptosis. ROS generation increased in a dose-dependent manner in all tested doses. APh activity was found to decrease in 1-100 microM UN-treated cells vs. controls. Our results show that UN modifies osteoblast cell metabolism by increasing ROS generation and reducing APh activity, suggesting that ROS may play a more complex role in cell physiology than simply causing oxidative damage.

Asunto(s)

Osteoblastos/efectos de los fármacos , Osteoblastos/ultraestructura , Nitrato de Uranilo/farmacología , Fosfatasa Alcalina/metabolismo , Animales , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Retículo Endoplásmico Rugoso/ultraestructura , Femenino , Investigación Fetal , Humanos , Inyecciones Intraperitoneales , Masculino , Microscopía Electrónica , Osteoblastos/metabolismo , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Acetato de Tetradecanoilforbol/administración & dosificación , Acetato de Tetradecanoilforbol/farmacología , Acetato de Tetradecanoilforbol/toxicidad , Tibia/citología , Tibia/metabolismo , Tibia/ultraestructura , Factores de Tiempo , Nitrato de Uranilo/administración & dosificación , Nitrato de Uranilo/toxicidad

RESUMEN

Objetivo. Describir las tendencias en el uso de fármacos antihipertensivos y comprobar la adecuación del tratamiento antihipertensivo en función de las condiciones asociadas según criterios del JNC-VI. Diseño. Se realizó un estudio prospectivo y retrospectivo sobre una muestra de la totalidad de la población hipertensa. Emplazamiento. Centro de salud urbano de Zaragoza. Pacientes. El estudio se desarrolló en un centro de salud urbano de Zaragoza que atiende una población de 23.332 personas. De los 3.820 hipertensos registrados en el fichero informático, se hizo un muestreo aleatorio sistemático y se seleccionaron 376 casos. Mediciones y resultados principales. Se obtuvieron datos sobre la evolución de la presión arterial, los fármacos utilizados y las patologías asociadas. La hipercolesterolemia y la obesidad fueron los factores de riesgo más frecuentes en los hipertensos. La enfermedad vascular periférica y la insuficiencia cardíaca fueron las enfermedades cardiovasculares de mayor prevalencia. Sólo un 7,7 por ciento de los hipertensos no presentó patología asociada. Los inhibidores de la enzima de conversión de la angiotensina y los bloqueantes de los canales del calcio han sido los fármacos que han experimentado mayor crecimiento en los últimos 12 años. El uso de diuréticos y betabloqueantes permanece estable en este centro. En el 36,13 por ciento de casos (n = 129) el tratamiento farmacológico no fue adecuado. En 30 pacientes el tratamiento prescrito no estaba indicado y en 99 el tratamiento indicado no fue prescrito. Conclusiones. El uso de los fármacos antihipertensivos no se corresponde completamente con la patología asociada. El tratamiento farmacológico de la hipertensión arterial puede optimizarse mejor si se tienen en cuenta las condiciones asociadas en todos los casos (AU)

Asunto(s)

Adulto , Anciano , Femenino , Masculino , Persona de Mediana Edad , Humanos , Antihipertensivos/uso terapéutico , Utilización de Medicamentos , Estudios Prospectivos , Estudios Retrospectivos , Resultado del Tratamiento