Bioaccessible heavy metals-sediment particles from Reconquista River induce lung inflammation in mice

The Reconquista River (RR), one of the most polluted watercourses in Argentina, receives effluent discharges from heavily industrialized and highly populated settlements. During winter and summer, the floodplain remains dry, producing the oxidation of sulfide and organic matter present in the sediment, making heavy metals more bioaccessible. Dispersion of this sediment occurs, and thus harmful effects on the pulmonary health of residents and workers inhabiting the RR bank may take place. The authors characterized the sediment particles of the RR (RR-PM) morphologically by scanning electron microscopy and its elemental composition by energy dispersive X-ray spectroscopy (EDX) and Community Bureau of Reference (BCR) sequential extraction. Furthermore, the authors evaluated its biological impact on the respiratory system of BALB/c mice, generating four groups: control healthy, sensibilized with ovalbumin, exposed to particles, and sensibilized and exposed to particles. Sediment particles of the Reconquista River contained fine particulate matter, with a high concentration of bioaccessible Cu and Zn. The authors found that animal exposure to RR-PM caused polymorphonuclear cell lung infiltration, augmentation of O2-, increase of proinflammatory cytokines (tumor necrosis factor alpha [TNFα], interleukin-6 [IL-6]) and apoptosis. This adverse response was more dramatic in the sensibilized and exposed to particles group. Even more, they proved the bioaccessible fraction present in the RR-PM to be responsible for these harmful effects. The authors conclude that RR-PM produces an adverse biological impact on the airways of healthy animals, which is largely aggravated in previously sensibilized animals.Fil: Ferraro, Sebastián Ariel. Universidad Nacional de San Martín. Instituto de Investigación e Ingeniería Ambiental. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación e Ingeniería Ambiental; ArgentinaFil: Curutchet, Gustavo Andres. Universidad Nacional de San Martín. Instituto de Investigación e Ingeniería Ambiental. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación e Ingeniería Ambiental; ArgentinaFil: Tasat, Deborah Ruth. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Histología y Embriología; Argentin

Systemic and Local Tissue Response to Titanium Corrosion

No metal or alloy is completely inert in vivo. Whether noble or passivated, all metals willsuffer a slow removal of ions from the surface, largely because of local and temporalvariations in microstructure and environment. The potential risk of corrosion and thepossible detrimental consequences of corrosion byproducts to tissues are issues of clinicalimportance. The biologic effect of corrosion is a public health concern for the community of patients who have a prosthesis (orthopedic and/or dental), since these prostheses remain inside the body over long periods of time. Evaluation of tissues around metallic devices is important since the presence of ions/particles and their potential local biological effects might affect implant outcome.Corrosion is one of the possible causes of implant failure after initial success. Metalcorrosion can affect close contact between the implant and the bone tissue(osseointegration).The issue of corrosion is not only a local problem since particles resulting from this processcould migrate systemically and deposit in target organs. The long term effects of thesedeposits are yet to be clarified. Mineral elements play a critical role in the physiology andpathology of biological systems. Titanium is a nonessential element; thus, the presence oftitanium in the body, titanium biokinetics, and the potential biological effects of titanium areof great interest to researchers. “In situ” degradation of a metallic implant is an unwanted event since it alters the structural integrity of the implant. Implant manufacturers must attempt to develop methods that reduce the diffusion of metal into the tissues in order to minimize the deleterious effects of corrosion.We believe further investigation, in particular long-term research, is necessary to advance inthe understanding of the factors involved in implant corrosion and establish basicguidelines for their use in clinical implantology. Handling and controlling corrosion of aSystemic and Local Tissue Response to Titanium Corrosion 109biomedical implant is essential from a biological, sanitary, metallurgic, economic, and socialviewpoint. Lastly, it is important to highlight that the adverse effects of corrosion described in thepresent chapter will not invariably occur in all patients with implants since biologicalresponse varies among individuals.Fil: Olmedo, Daniel Gustavo. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Anatomía Patológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Tasat, Deborah. Universidad de Buenos Aires; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; ArgentinaFil: Duffó, Gustavo Sergio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Cabrini, Rómulo. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Anatomía Patológica; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Guglielmotti, Maria Beatriz. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Anatomía Patológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin

Particulate matter cytotoxicity in cultured SH-SY5Y cells is modulated by simvastatin: Toxicological assessment for oxidative damage

Epidemiological studies have shown a positive correlation between environmental particulate matter and adverse health effects. In particular, residual oil fly ash (ROFA) induces inflammation and reactive oxygen species (ROS), exerting not only local, but also systemic adverse effects. Previously, in an experimental animal model, we found that simvastatin (Sv) pretreatment was effective in preventing ROFA induced lung inflammation. Herein, using the human neuroblastoma SH-SY5Y cell line as a neurotoxicity in vitro model, we studied the potential Sv protective effect on ROFA cytotoxicity. We evaluated cell viability by the MTT assay, superoxide anion generation by NBT test, Nrf2 activation by immunofluorescence, apoptosis by cleaved-PARP and active-caspase 3 expressions, and senescence by b-galactosidase activity. SH-SY5Y cells exposed to ROFA (10 and 50mg/ml) for 24 h showed decreased cell viability, increased superoxide anion generation, apoptosis and senescence. Pretreatment with Sv (1mM) for 6 days, restored cell viability to basal levels, reduced ROFA-induced O2 generation as well as the number of apoptotic and senescent cells. Sv pretreatment stimulated the basal and ROFA-induced levels of Nrf2 nuclear translocation suggesting that activation of the cellular antioxidant defense system prevented particle-induced oxidative stress. In parallel, rescue experiments with mevalonate did not modify the effects of SV pretreatment in any of the parameters evaluated in this study. We conclude that simvastatin may provide neuroprotection against air particulate matter-induced neurotoxicity independently of its ability to inhibit cholesterol synthesis.Fil: Ferraro, Sebastián Ariel. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología. Centro de Estudios en Salud y Medio Ambiente; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Astort, Francisco. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología. Centro de Estudios en Salud y Medio Ambiente; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Yakisich, Juan Sebastian. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología. Centro de Estudios en Salud y Medio Ambiente; ArgentinaFil: Tasat, Deborah Ruth. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología. Centro de Estudios en Salud y Medio Ambiente; Argentina. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Histología y Embriología; Argentin

Direct and indirect air particle cytotoxicity in human alveolar epithelial cells

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 24h 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 (TNF α, 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.Fil: Orona, Nadia Soledad. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Astort, Francisco. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Maglione, Guillermo Alberto. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Saldiva, P. H. N.. Iira, National Research Council, Brazil; . Institute of Integrated Risk Analysis; BrasilFil: Yakisich, J. S.. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Tasat, Deborah Ruth. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Universidad de Buenos Aires. Facultad de Odontología; Argentin

Nanotecnología: ¿Revolución científico-tecnológica de pequeños riesgos?

La nanotecnología es un campo de las ciencias aplicadas dedicado al control y manipulación de la materia a nivel de átomos y moléculas, en un rango comprendido entre uno y cien nanómetros. Permite la creación de materiales, dispositivos y sistemas mediante el control de la materia a esa escala. En el campo de la Odontología se han desarrollado bio-sensores altamente especializados, que permitirían la identificación de enfermedades en la saliva. En un futuro cercano será clave su uso en el diagnóstico de enfermedades de alto impacto como el cáncer de mama, ovario y páncreas, enfermedad de Alzheimer, SIDA, diabetes y osteoporosis.Fil: Olmedo, Daniel Gustavo. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Anatomía Patologica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Tasat, Deborah R.. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Odontología; ArgentinaFil: Cabrini, Rómulo L.. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Anatomía Patologica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Audebert, Fernando Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ingeniería. Departamento de Ingeniería Mecánica; ArgentinaFil: Guglielmotti, Maria Beatriz. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Anatomía Patologica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Volcanic ash from Puyehue-Cordón Caulle Volcanic Complex and Calbuco promote a differential response of pro-inflammatory and oxidative stress mediators on human conjunctival epithelial cells

Volcanic ash could pose a hazard to the ocular surface as it is constantly exposed to environmental particles. We exposed conjunctival cells to Puyehue-Cordón Caulle volcanic complex (PCCVC) or Calbuco ash particles and evaluated proliferation, viability, apoptosis, MUC1 expression, pro-inflammatory cytokines, and oxidative stress markers. Ash particles from these volcanoes vary in size, composition, and morphology. Our results demonstrate that PCCVC but not Calbuco ash particles induce cytotoxicity on human conjunctival epithelial cells viewed as a decrease in cell proliferation and the transmembrane mucin MUC1 expression; a pro-inflammatory response mediated by IL-6 and IL-8; and an imbalance of the redox environment leading to protein oxidative damage. This is the first in vitro study that assesses the biological effect of volcanic ash particles on human conjunctival epithelial cells and the involvement of inflammatory mediators and oxidative stress as the mechanisms of damage. Our results could provide a better understanding of the ocular symptoms manifested by people living near volcanic areas.Fil: Tesone, Agustina I.. Universidad de Buenos Aires; ArgentinaFil: Lasagni Vitar, Romina Mayra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Tau, Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Maglione, Guillermo Alberto. Universidad de Buenos Aires; Argentina. Universidad Nacional de San Martín; ArgentinaFil: Llesuy, Susana Francisca. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Tasat, Deborah Ruth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina. Universidad Nacional de San Martín; ArgentinaFil: Berra, Alejandro. Universidad de Buenos Aires; Argentin

Bisphosphonates as Chelating Agents in Uranium Poisoning

The study of uranium toxicity is very important for public health in general and especially for workers involved in the processes of uranium mining and milling because of the immediate and/or mediate risks of exposure. Most available studies show unsuccessful attempts to eliminate uranium from target organs once the poisoning has occurred. Our group has managed to avoid damage to target organs (short-term kidney and long-term bone damage) in a high percentage of animals treated with lethal doses of uranyl nitrate through the effective chelating action of a single dose of bisodic etidronate. In this context, the contributions of our team and other groups working on chelating therapies provide a starting point for progress in the search for agents for preventing and/or reducing the toxic effects of uranium

NADPH oxidase and mitochondria are relevant sources of superoxide anion in the oxinflammatory response of macrophages exposed to airborne particulate matter

Exposure to ambient air particulate matter (PM) is associated with increased cardiorespiratory morbidity and mortality. In this context, alveolar macrophages exhibit proinflammatory and oxidative responses as a result of the clearance of particles, thus contributing to lung injury. However, the mechanisms linking these pathways are not completely clarified. Therefore, the oxinflammation phenomenon was studied in RAW 264.7 macrophages exposed to Residual Oil Fly Ash (ROFA), a PM surrogate rich in transition metals. While cell viability was not compromised under the experimental conditions, a proinflammatory phenotype was observed in cells incubated with ROFA 100 μg/mL, characterized by increased levels of TNF-α and NO production, together with PM uptake. This inflammatory response seems to precede alterations in redox metabolism, characterized by augmented levels of H2O2, diminished GSH/GSSG ratio, and increased SOD activity. This scenario resulted in increased oxidative damage to phospholipids. Moreover, alterations in mitochondrial respiration were observed following ROFA incubation, such as diminished coupling efficiency and spare respiratory capacity, together with augmented proton leak. These findings were accompanied by a decrease in mitochondrial membrane potential. Finally, NADPH oxidase (NOX) and mitochondria were identified as the main sources of superoxide anion ([Formula presented]) in our model. These results indicate that PM exposure induces direct activation of macrophages, leading to inflammation and increased reactive oxygen species production through NOX and mitochondria, which impairs antioxidant defense and may cause mitochondrial dysfunction

Monitoring human genotoxicity risk associated to urban and industrial Buenos Aires air pollution exposure

The quality of life in large megacities is directly affected by its air quality. In urban environments, suspended particles from anthropogenic origin is one of the main air contaminants identified as highly genotoxic, mutagenic, or carcinogenic. Atmospheric monitoring is therefore imperative, and bioassays to detect the effects of genotoxic agents give usually excellent results. Analysis of micronucleus (MN) in exfoliated oral mucosa cells is a sensitive non-invasive method for monitoring genetic damage in human populations. The first aim of this study was to analyze and characterize levels of volatile organic compounds (VOCs), particulate matter (PM), and polycyclic aromatic hydrocarbons (PAHs) in two areas from Buenos Aires: La Plata city, an urban (U) area and Ensenada, an industrial (I) area. Secondly, we evaluated the possible health risk of its inhabitants through a simple genotoxic assay on exfoliated oral mucosa cells. Whole blood cell count and nuclear abnormalities frequencies were evaluated in the exfoliated oral mucosa cells from urban and industrial inhabitants. Smoking habit represented a significant factor increasing MN percentage while, age did not increase the production of any of the nuclear aberrations assayed (micronuclei, binucleated, karyorrhexis) when the inhabitants from the urban and the industrial areas were compared. In addition, changes in MN and binucleated cell percentages in males and females were found to be area-dependent. We suggest that regardless PM concentration, PM-specific characteristics (size, shape, chemical elements, etc.) and VOCs levels could be responsible for the different harmful genotoxic effects seen in the two areas. Although this is a preliminary study, our results allowed to recognize that individuals living in both the urban and the industrial areas could be considered susceptible groups and should periodically undergo biological monitoring and appropriate care.Centro de Investigaciones del MedioambienteCentro de Investigación y Desarrollo en Ciencias Aplicada

Acute exposure to air pollution particulate matter aggravates experimental myocardial infarction in mice by potentiating cytokine secretion from lung macriphages

Clinical, but not experimental evidence has suggested that air pollution particulate matter (PM) aggravates myocardial infarction (MI). Here, we aimed to describe mechanisms and consequences of PM exposure in an experimental model of MI. C57BL/6J mice were challenged with a PM surrogate (Residual Oil Fly Ash, ROFA) by intranasal installation before MI was induced by permanent ligation of the left anterior descending coronary artery. Histological analysis of the myocardium 7 days after MI demonstrated an increase in infarct area and enhanced inflammatory cell recruitment in ROFA-exposed mice. Mechanistically, ROFA exposure increased levels of the circulating pro-inflammatory cytokines TNF-α, IL-6, and MCP-1, activated myeloid and endothelial cells, and enhanced leukocyte recruitment to the peritoneal cavity and the vascular endothelium. Notably, these effects on endothelial cells and circulating leukocytes could be reversed by neutralizing anti-TNF-α treatment. We identified alveolar macrophages as the primary source of elevated cytokine production after PM exposure. Accordingly, in vivo depletion of alveolar macrophages by intranasal clodronate attenuated inflammation and cell recruitment to infarcted tissue of ROFA-exposed mice. Taken together, our data demonstrate that exposure to environmental PM induces the release of inflammatory cytokines from alveolar macrophages which directly worsens the course of MI in mice. These findings uncover a novel link between air pollution PM exposure and inflammatory pathways, highlighting the importance of environmental factors in cardiovascular disease.Fil: Marchini, Timoteo Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Wolf, Dennis. University Of Freiburg; AlemaniaFil: Anto Michel, Nathaly. University Of Freiburg; AlemaniaFil: Mauler, Maximilian. University Of Freiburg; AlemaniaFil: Dufner, Bianca. University Of Freiburg; AlemaniaFil: Hoppe, Natalie. University Of Freiburg; AlemaniaFil: Beckert, Jessica. University Of Freiburg; AlemaniaFil: Jäekel, Markus. University Of Freiburg; AlemaniaFil: Magnani, Natalia Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Duerschmied, Daniel. University Of Freiburg; AlemaniaFil: Tasat, Deborah Ruth. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología. Centro de Estudios en Salud y Medio Ambiente; ArgentinaFil: Alvarez, Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Reinöhl, Jochen. University Of Freiburg; AlemaniaFil: von zur Muhlen, Constantin. University Of Freiburg; AlemaniaFil: Idzko, Marco. University Of Freiburg; AlemaniaFil: Bode, Christoph. University Of Freiburg; AlemaniaFil: Hilgendorf, Ingo. University Of Freiburg; AlemaniaFil: Evelson, Pablo Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Zirlik, Andreas. University Of Freiburg; Alemani