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

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

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

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

Efecto de la inhalación de las partículas aéreas de la Ciudad de Buenos Aires: Alteraciones histomorfológicas, metabólicas y bioquímicas a nivel pulmonar y extra pulmonar en ratones jóvenes y adultos mayores

Introducción: Numerosos estudios han demostrado que la contaminación del aire se asocia a efectos adversos para la salud. Específicamente, datos epidemiológicos muestran asociación entre la exposición al material partículado aéreo (MP) e incrementos en la morbo-mortalidad por enfermedades cardiopulmonares. Las partículas de menor tamaño pueden ser traslocadas desde los pulmones a la circulación y afectar órganos extrapulmonares como corazón e hígado. Sin embargo, el MP no afecta de igual manera a todas las personas, siendo la edad un parámetro que puede influir en los efectos del MP sobre la salud. Objetivo: Estudiar in vivo en dos poblaciones etarias (ratones jóvenes y envejecidos) los mecanismos biológicos mediante los cuales las partículas aéreas de la Ciudad de Buenos Aires (UAP-BA) podrían inducir efectos adversos en el sistema respiratorio y en órganos extrapulmonares. Materiales y Métodos: Se emplearon ratones BALB/c jóvenes (3 meses de edad) o envejecidos (9 meses de edad) y se expusieron mediante instilación intranasal a UAP-BA o ROFA (sucedáneo de la contaminación aérea). Se analizó la respuesta biológica en pulmón, corazón e hígado a nivel metabólico (parámetros oxidativos e inflamatorios), bioquímico (biomarcadores séricos) e histomorfológicos a las 3, 24 y 48 hs post-instilación. Resultados: Ambos MP provocaron una respuesta inflamatoria local y sistémica. En el pulmón, histológicamente se observó una reducción del área alveolar, en el corazón inflamación epicárdica y en el hígado inflamación y esteatosis con aumento en los niveles de enzimas transaminasas séricas en ambos grupos etarios. Conclusión: Demostramos que UAP-BA, en un modelo experimental murino, altera no sólo el sistema respiratorio sino también órganos extrapulmonares como corazón e hígado. Por ello, hipotetizamos que UAP-BA podría potencialmente provocar una respuesta biológica adversa similar en individuos jóvenes y adultos que habitan la Ciudad de Buenos Aires.Introduction: Numerous studies have shown that air pollution is consistently associated with adverse health effects. Epidemiological data have specifically shown an association between the exposure to air particulate matter (PM) and an increase in cardiorespiratory morbidity/mortality. Smaller particles can be translocated from the lungs into the circulation and affect extrapulmonary organs such as the heart and liver. However, PM does not equally impact all the population, since the effects of MP on health may be influenced by age. Objective: to study in vivo the biological mechanisms by which Buenos Aires Urban Air Particles (UAP-BA) could induce adverse effects on the respiratory system and extrapulmonary organs of young and adult mice. Materials and Methods: young (3 months d) and adult (9 months old) BALB/c mice were exposed to UAP-BA or ROFA (surrogate of airborne contamination) by intranasal instillation. In the lung, heart and liver, the biological response was assessed metabolically (oxidative and inflammatory parameters), biochemically (serum biomarkers), and histomorphologically at 3, 24 and 48 h post-instillation. Results: both types of PM caused local and systemic inflammatory response. Histologically, we observed a reduction of the alveolar area in the lung, heart epicardial inflammation, and liver inflammation and steatosis with an increase in the levels of serum transaminases in both age groups. Conclusions: we showed in a murine experimental model that UAP-BA altered not only the respiratory system but also extrapulmonary organs such as the heart and liver. Therefore, we hypothesized that UAP-BA could potentially induce similar adverse biological effects on young and adult individuals living in the City of Buenos Aires.Fil: Orona, Nadia Soledad. 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: 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: Maglione, Guillermo Alberto. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología. Centro de Estudios en Salud y Medio Ambiente; ArgentinaFil: Kurtz, Melisa Lidia Amelia. 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: Agosta, Eduardo Germán. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología. Centro de Estudios en Salud y Medio Ambiente; ArgentinaFil: Mandalunis, Patricia Mónica. Universidad de Buenos Aires; ArgentinaFil: Morales, Celina. Universidad de Buenos Aires; ArgentinaFil: Tasat, Deborah Ruth. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología. Centro de Estudios en Salud y Medio Ambiente; Argentin

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

In vivo short-term exposure to residual oil fly ash impairs pulmonary innate immune response against environmental mycobacterium infection

Epidemiological studies have shown that pollution derived from industrial and vehicular transportation induces adverse health effects causing broad ambient respiratory diseases. Therefore, air pollution should be taken into account when microbial diseases are evaluated. Environmental mycobacteria (EM) are opportunist pathogens that can affect a variety of immune compromised patients, which impacts significantly on human morbidity and mortality. The aim of this study was to evaluate the effect of residual oil fly ash (ROFA) pre-exposure on the pulmonary response after challenge with opportunistic mycobacteria by means of an acute short-term in vivo experimental animal model. We exposed BALB/c mice to ROFA and observed a significant reduction on bacterial clearance at 24 h post infection. To study the basis of this impaired response four groups of animals were instilled with (a) saline solution (Control), (b) ROFA (1 mg kg21 BW), (c) ROFA and EM-infected (Mycobacterium phlei, 8 3 106 CFU), and (d) EMinfected. Animals were sacrificed 24 h postinfection and biomarkers of lung injury and proinflammatory madiators were examined in the bronchoalveolar lavage. Our results indicate that ROFA was able to produce an acute pulmonary injury characterized by an increase in bronchoalveolar polymorphonuclear (PMN) cells influx and a rise in O2 2 generation. Exposure to ROFA before M. phlei infection reduced total cell number and caused a significant decline in PMN cells recruitment (p<0.05), O2 2 generation, TNFa (p<0.001), and IL-6 (p<0.001) levels. Hence, our results suggest that, in this animal model, the acute short-term pre-exposure to ROFA reduces early lung response to EM infectionInstituto de BiotecnologíaFil: Delfosse, Verónica Cecilia. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; ArgentinaFil: Tasat, Deborah Ruth. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Histología y Embriología; ArgentinaFil: Gioffre, Andrea. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentin

In vivo short-term exposure to residual oil fly ash impairs pulmonary innate immune response against environmental mycobacterium infection

Epidemiological studies have shown that pollution derived from industrial and vehicular transportation induces adverse health effects causing broad ambient respiratory diseases. Therefore, air pollution should be taken into account when microbial diseases are evaluated. Environmental mycobacteria (EM) are opportunist pathogens that can affect a variety of immune compromised patients, which impacts significantly on human morbidity and mortality. The aim of this study was to evaluate the effect of residual oil fly ash (ROFA) pre-exposure on the pulmonary response after challenge with opportunistic mycobacteria by means of an acute short-term in vivo experimental animal model. We exposed BALB/c mice to ROFA and observed a significant reduction on bacterial clearance at 24 h post infection. To study the basis of this impaired response four groups of animals were instilled with (a) saline solution (Control), (b) ROFA (1 mg kg−1 BW), (c) ROFA and EM-infected (Mycobacterium phlei, 8 × 106 CFU), and (d) EM-infected. Animals were sacrificed 24 h postinfection and biomarkers of lung injury and proinflammatory madiators were examined in the bronchoalveolar lavage. Our results indicate that ROFA was able to produce an acute pulmonary injury characterized by an increase in bronchoalveolar polymorphonuclear (PMN) cells influx and a rise in O2− generation. Exposure to ROFA before M. phlei infection reduced total cell number and caused a significant decline in PMN cells recruitment (p < 0.05), O2− generation, TNFα (p < 0.001), and IL-6 (p < 0.001) levels. Hence, our results suggest that, in this animal model, the acute short-term pre-exposure to ROFA reduces early lung response to EM infection.Fil: Delfosse, Verónica Cecilia. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; ArgentinaFil: Tasat, Deborah Ruth. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Histología y Embriología; ArgentinaFil: Gioffré, Andrea Karina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentin