Aerobic Exercise Attenuated Bleomycin-Induced Lung Fibrosis in Th2-Dominant Mice

Introduction The aim of this study was to investigate the effect of aerobic exercise (AE) in reducing bleomycin- induced fibrosis in mice of a Th2-dominant immune background (BALB/c). Methods BALB/c mice were distributed into: sedentary, control (CON), Exercise-only (EX), sedentary, bleomycin-treated (BLEO) and bleomycin-treated+exercised (BLEO+EX);(n = 8/group). Following treadmill adaptation, 15 days following a single, oro-tracheal administration of bleomycin (1.5U/kg), AE was performed 5 days/week, 60min/day for 4 weeks at moderate intensity (60% of maximum velocity reached during a physical test) and assessed for pulmonary inflammation and remodeling, and cytokine levels in bronchoalveolar lavage (BAL). Results At 45 days post injury, compared to BLEO, BLEO+EX demonstrated reduced collagen deposition in the airways (p<0.001) and also in the lung parenchyma (p<0.001). In BAL, a decreased number of total leukocytes (p<0.01), eosinophils (p<0.001), lymphocytes (p<0.01), macrophages (p<0.01), and neutrophils (p<0.01), as well as reduced pro-inflammatory cytokines (CXCL-1;p<0.01), (IL-1 beta;p<0.001), (IL-5;p<0.01), (IL-6;p<0.001), (IL-13;p<0.01) and pro-fibrotic growth factor IGF-1 (p<0.001) were observed. Anti-inflammatory cytokine IL-10 was increased (p<0.001). Conclusion AE attenuated bleomycin-induced collagen deposition, inflammation and cytokines accumulation in the lungs of mice with a predominately Th2-background suggesting that therapeutic AE (15-44 days post injury) attenuates the pro-inflammatory, Th2 immune response and fibrosis in the bleomycin model

Aerobic exercise inhibits acute lung injury: from mouse to human evidence Exercise reduced lung injury markers in mouse and in cells

Acute respiratory distress syndrome (ARDS) is defined as hypoxemic respiratory failure with intense pulmonary inflammation, involving hyperactivation of endothelial cells and neutrophils. Given the anti-inflammatory effects of aerobic exercise (AE), this study investigated whether AE performed daily for 5 weeks would inhibit extra-pulmonary LPS-induced ARDS. C57Bl/6 mice were distributed into Control, Exercise, LPS and Exercise+ LPS groups. AE was performed on a treadmill for 5x/week for four weeks before LPS administration. 24hours after the final AE physical test, animals received 100ug of LPS intra-peritoneally. In addition, whole blood cell culture, neutrophils and human endothelial cells were pre-incubated with IL-10, an anti-inflammatory cytokine induced by exercise. AE reduced total protein levels (p<0.01) and neutrophil accumulation in bronchoalveolar lavage (BAL) (p<0.01) and lung parenchyma (p<0.01). AE reduced BAL inflammatory cytokines IL-1 beta, IL-6 and GM-CSF (p<0.001), CXCL1/KC, IL-17, TNF-alpha and IGF-1 (p<0.01). Systemically, AE reduced IL-1 beta, IL-6 and IFN-gamma (p<0.001), CXCL1/KC (p<0.01) and TNF-alpha (p<0.05). AE increased IL-10 levels in serum (p<0.001) and BAL (p<0.001). Furthermore, AE increased superoxide dismutase SOD (p<0.01) and decreased superoxide anion accumulation in the lungs (p<0.01). Lastly, pre-incubation with IL-10 significantly reduced LPS-induced activation of whole blood cells, neutrophils and HUVECs, as observed by reduced production of IL-1 beta, IL-6, IL-8 and TNF-alpha. Our data suggest that AE inhibited LPS-induced lung inflammation by attenuating inflammatory cytokines and oxidative stress markers in mice and human cell culture via enhanced IL-10 production.Sao Paulo Research Foundation (FAPESP) [2012/15165-2]Conselho Nacional de Pesquisa e Desenvolvimento (CNPq) [311335-2015-2]Comissao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) [12804/13-4, 1303/13-9]FAPESP [2013/24076-6, 2014/23196-0, 2012/14604-8, 2012/25435-7, 2012/24880-7]CAPESNove Julho Univ, Sao Paulo, SP, BrazilBrazilian Inst Teaching & Res Pulm & Exercise Imm, Sao Jose Dos Campos, SP, BrazilFed Univ Sao Paulo UNIFESP, Postgrad Program Sci Human Movement & Rehabil, Santos, SP, BrazilUniv Brasil, Sao Paulo, SP, BrazilUniv Sao Paulo, Sch Med, Dept Pathol LIM 59, Sao Paulo, SP, BrazilUniv Fed Lavras UFLA, Sci Dept Hlth, Lavras, MG, BrazilFed Univ Sao Paulo UNIFESP, Campus Sao Paulo, Sao Paulo, SP, BrazilHarbor UCLA Med Ctr, Div Resp & Crit Care Physiol & Med, Los Angeles Biomed Res Inst, Torrance, CA 90509 USAUniv Tubingen, Inst Clin & Expt Transfus Med IKET, Tubingen, GermanyFed Univ Sao Paulo UNIFESP, Postgrad Program Sci Human Movement & Rehabil, Santos, SP, BrazilFed Univ Sao Paulo UNIFESP, Campus Sao Paulo, Sao Paulo, SP, BrazilFAPESP [2012/15165-2]CNPq [311335-2015-2]CAPES [12804/13-4, 1303/13-9]FAPESP [2013/24076-6, 2014/23196-0, 2012/14604-8, 2012/25435-7, 2012/24880-7]Web of Scienc

Stereological study of the effect of gestational exposure to environmental pollution in São Paulo on kidney development in mice

A poluição atmosférica é um importante fator de risco à saúde humana, com maior vulnerabilidade em pessoas com doenças pré-existentes, idosos, crianças e fetos. A teoria da origem desenvolvimentista da saúde e doença se baseia em evidências que alterações no desenvolvimento fetal que podem levar a prematuridade, baixo peso ao nascer e predispor ao surgimento de síndrome metabólica, hipertensão e doenças renais na idade adulta. Há evidências também que alterações do ambiente intrauterino na gestação afetam o número de néfrons ao nascimento, o que predispõe à hipertensão na idade adulta. Estudos experimentais prévios comprovam que o ar de São Paulo apresenta uma concentração de poluentes capaz de desencadear, além de lesões cardio-respiratórias, alterações reprodutivas como baixo peso ao nascer e prematuridade. O objetivo deste estudo foi avaliar de maneira objetiva se a exposição aos níveis ambientais de poluição atmosférica no período gestacional tem o potencial de promover alterações de volume renal e número de glomérulos ao nascimento, o que, com base na teoria da origem fetal das doenças, poderia ser um fator predisponente para doenças renais e hipertensão no adulto. Para tanto, neste estudo, foram estudados rins fetos de camundongos Balb/c no 18º dia pós-concepção, expostos aos níveis ambientais de poluição do ar em São Paulo, em duas câmaras de exposição uma recebendo ar filtrado (F) e outra ar não filtrado (P). Os rins dos fetos foram avaliados morfologicamente por métodos estereológicos para estimativa do volume renal total e de cada compartimento (córtex e medula) e número de néfrons. A concentração do material particulado na câmara filtrada foi significantemente menor (71%, p<0.001) que na câmara não filtrada. O peso fetal e dos rins foi 30% menor no grupo NF em relação ao grupo F (p=0.007 e p=0,0112 respectivamente). iv Doutorado Nilsa Regina Damaceno-Rodrigues 2012 O córtex e a medula renais dos fetos do grupo NF apresentaram redução de volume: córtex: 4,46±0,55 x 2,44±0,79 (p=0,0003); medula: 2,35±0,43 x 1,24±0,61 (p=0,0034). O número absoluto de néfrons no rim dos fetos NF (3301,0±1720,8) foi significantemente menor (p=0,0082) que nos fetos F (7199,5±2023,5). Estes dados mostram que a exposição pré-natal aos níveis ambientais de poluição em São Paulo provoca uma alteração no desenvolvimento renal, que pode levar à doenças no adultoAir pollution is an important risk factor to human health, with greater vulnerability in people with pre-existing diseases, elderly, children and fetuses. The theory of developmental origins of health and illness proposes that changes in fetal development that can lead to prematurity, low birth weight and predisposition to chronic diseases in adulthood. There is also evidence that changes in the intrauterine environment during pregnancy affect the number of nephrons at birth, which predisposes to hypertension in adulthood. Previous experimental studies show that the air of Sao Paulo has a concentration of pollutants that can trigger cardio-respiratory lesions and reproductive hindrances as low birth weight and prematurity. Our proposal was to evaluate objectively whether exposure to ambient levels of air pollution during pregnancy has the potential to promote changes in renal volume and number of glomeruli at birth, which could be a predisposing factor for adult renal illness and hypertension based on the theory of fetal origin of the disease. Therefore, in this study, we used kidneys of fetal Balb/c mice on day 18 post-conception (dpc), exposed to ambient levels of air pollution in Sao Paulo in two exposure chambers: one receiving filtered air (F) and other non-filtered air (P). The kidneys of the fetuses were morphologically evaluated by stereological methods for estimation of total renal volume and the volume of each compartment (cortex and medulla) and the number of nephrons. The concentration of particulate matter in the filtered chamber was significantly lower (71%, p<0.001) than in the unfiltered chamber. Fetal weight and kidney weight were 30% lower in the unfiltered chamber (p=0.007 and p=0.0112 respectively). The renal cortex and medulla of exposed fetuses showed volume reduction; cortex: 4.46 ± 0.55 x 2.44 ± Doutorado Nilsa Regina Damaceno-Rodrigues 2012 0.79 (p=0.0003); medulla: 2.35 ± 0.43 x 1.24 ± 0.61 (p=0.0034). The absolute number of nephrons in the kidney of exposed fetuses (3301,0±1720,8) was significantly lower (p=0.0082) when compared to the filtered air group (7199,5±2023,5). These data show that pre-natal exposure to ambient levels of air pollution in Sao Paulo entails changes in the development of the kidney, that can lead to illness in adult age

Measurements of oxidative stress indicators and of cardiac remodeling in mice exposed to urban air pollution during embrionary and postnatal development.

A poluição atmosférica de São Paulo (SP) pode provocar alterações cardiovasculares em seres humanos e animais experimentais, com maior vulnerabilidade em crianças e fetos. O mecanismo fisiopatológico que explicaria a relação entre a exposição aos poluentes e doenças cardiovasculares não está totalmente estabelecido, sendo que o estresse oxidativo pode estar ligado ao dano e morte celular. Há evidências de que o dano oxidativo pelo mecanismo da peroxidação lipídica pode estar relacionado às causas de diversas cardiovasculopatias. Estudamos o efeito da exposição ao ar ambiental nos níveis de peroxidação lipídica no coração de camundongos nos períodos pré e pós-natal. Os animais foram mantidos em duas câmaras de exposição, uma recebendo ar ambiente e outra ar filtrado, em quatro diferentes grupos: 1) LL: gestados e crescidos em câmara com ar filtrado, 2) PP: gestados e crescidos em câmara com ar poluído de SP, 3) PL: gestados na câmara poluída e crescidos na limpa, e 4) LP: gestados na câmara limpa e crescidos na poluída. A peroxidação lipídica do miocárdio foi avaliada tanto pelo método TBA como por imunohistoquímica para 15-F2t-isoprostano. As concentrações de malondialdeído (MDA, indicador de peroxidação lipídica) foi maior nos animais PP quando comparados aos LL (p = 0,004) e PL (p = 0,026), e não mostrou diferença significativa em relação ao grupo LP (p = 0,894). Os valores de MDA para animais PL e LP mostraram-se equivalentes (p = 0,168). Chama a atenção que o grupo PL apresentou um valor de MDA maior que o LL (p = 0,026). A fração de volume de miocárdio marcada imunohistoquimicamente para 15- F2t-isoprostano apresentou valores maior em PL (p = 2,884x10-5), LP (p = 6,632x10-6) e PP (p = 5,45x10-8) que em LL. O valor de PP foi maior que os de PL e LP (p = 3,661x10-4 e 1,058x10-3, respectivamente), sendo esses últimos equivalentes entre si (p = 0,624). A análise ultra-estrutural mostrou de maneira consistente a presença de lisossomos secundários contendo estruturas lipídicas membranosas nos grupos LP e PP. A porcentagem média de arteríolas com área entre 200 e 1000 ?m² em relação ao número total de vasos de cada grupo foi maior no grupo PP do que nos grupos LL e PL (p=0,0387 e p=0,0362, respectivamente). Estes resultados sugerem que existem altos níveis de peroxidação lipídica no tecido cardíaco dos animais expostos ao ar ambiental de SP. Chama a atenção o fato de que a exposição intra-uterina ter implicado em níveis maiores de estresse oxidativo na fase adulta, mesmo com a melhoria das condições ambientais. Comparam-se estes achados no miocárdio a outros resultados da literatura.I t is well known that air pollution exposure in São Paulo can elicit cardiovascular injuries in humans and experimental animals and that children and fetuses appear to be particularly vulnerable. However, the mechanisms involved in this cardiovascular damage are not well understood. It has been suggested that the oxidative stress generated by air pollution exposure can trigger tissue injury. There is evidence supporting the idea that injury caused by lipid peroxidation may be related to the causes of several cardiovascular diseases. The aim of this study was to investigate the effects of prenatal and postnatal exposure to urban air pollution on the myocardium lipid peroxidation levels of adult mice. Myocardium lipid peroxidation was determined by the TBA method and by the detection of 15-F2t-isoprostan by immunohistochemical technique. The animals were placed in two chambers: one received air that passed through an air filter (clean) and the second received ambient air (polluted), according to four different exposure procedures: 1) Clean (CC): prenatal and postnatal in the clean chamber (control group), 2) Polluted (PP): prenatal and posnatal in the polluted chamber, 3) Polluted-clean (PC): prenatal in the polluted and posnatal in the clean chamber and 4) Clean-polluted (CP): prenatal in the clean and posnatal in the polluted chamber. The concentration of of malondialdehyde (MDA, a indicator of lipid peroxidation) was higher in group PP compared to CC (p = 0.004) and to PC (p = 0.026), and was not different of group CP (p = 0.894). The values of MDA for groups PC and CP turned to be equal (p = 0.168). Interestingly, group PC had a higher value of MDA than group CC (p = 0.026). The volume fraction of myocardium with detection of 15-F2tisoprostane is higher in PC (p = 2.884x10-5), CP (p = 6.632x10-6) and PP (p = 5.45x10-8) than in CC. The value of PP in higher than those of PC and CP (p = 3.661x10-4 and 1.058x10-3, respectively), while the latter two were equal to each other (p = 0.624). ). The mean ratio of arterioles wiht lumen area between 200 and 1000?m² to the total number of vessels in each group was higher in PP than in CC and PC (p=0.0387 and p=0.0362, respectively). These results, which suggest that exposure to air pollution is associated to higher levels of lipid peroxidation in the myocardium, are compared to other results previously published about respiratory and reproductive alterations related to pollution. Interestingly, the increased levels of lipid peroxidation in the PC group gives evidence that the prenatal exposure to urban air pollution can be linked to cardiovascular effects in adult life

Chronic exposure to fine particulate matter emitted by traffic affects reproductive and fetal outcomes in mice

Air pollution is an important environmental health risk factor that can result in many different gestational and reproductive negative outcomes. In this study, we have investigated the effects of two different times of exposure (before conception and during pregnancy) to urban ambient particulate matter on reproductive and pregnancy outcomes in mice. Using exposure chambers receiving filtered (F) and non-filtered (NF) air, we observed that exposed females exhibited changes in the length of estrus cycle and extended estrus and, therefore, a reduction in the number of cycles during the studied period (F2.6 +/- 0.22 and NF 1.2 +/- 0.29, p = 0.03). The mean number of antral follicles declined by 36% (p = 0.04) in NF mice (75 +/- 35.2) compared to F mice (118.6 +/- 18.4). our results further indicate a significant increase in time necessary for mating and decreased fertility and pregnancy indices (p = 0.003) in NF couples. Mean post-implantation loss rates were increased by 70% (p <= 0.005) in the NF2 group (exposed before and during pregnancy to NF air) compared to the F1 group (exposed before and during pregnancy to F air) and were influenced by both pre-gestational (p < 0.004) and gestational (p < 0.01) period exposure. Fetal weight was significantly higher in the F1 group when compared with the other groups (p < 0.001), at a 20% higher weight in the F1 group (0.86 +/- 0.18 g) than in the NF2 group (0.68 +/- 0.10g). Furthermore, fetal weight was influenced by both pre-gestational and gestational period exposure, and a significant interaction between these two factors was found (p < 0.001). This study demonstrated that exposure to ambient levels of urban traffic-generated particulate matter negatively affects different functions and stages of the reproductive process. Our results also reinforce the idea that maternal exposure to air pollution is linked to negative pregnancy outcomes, even if the exposure occurs only before conception. (C) 2009 Elsevier Inc. All rights reserved

Particulate urban air pollution affects the functional morphology of mouse placenta

in humans, adverse pregnancy outcomes (low birth weight, prematurity, and intrauterine growth retardation) are associated with exposure to urban air pollution. Experimental data have also shown that such exposure elicits adverse reproductive outcomes. We hypothesized that the effects of urban air pollution on pregnancy outcomes could be related to changes in functional morphology of the placenta. To test this, future dams were exposed during pregestational and gestational periods to filtered or nonfiltered air in exposure chambers. Placentas were collected from near-term pregnancies and prepared for microscopical examination. Fields of view on vertical uniform random tissue slices were analyzed using stereological methods. Volumes of placental compartments were estimated, and the labyrinth was analyzed further in terms of its maternal vascular spaces, fetal capillaries, trophoblast, and exchange surface areas. From these primary data, secondary quantities were derived: vessel calibers (expressed as diameters), trophoblast thickness (arithmetic mean), and total and mass-specific morphometric diffusive conductances for oxygen of the intervascular barrier. Two-way analysis of variance showed that both periods of exposure led to significantly smaller fetal weights. Pregestational exposure to nonfiltered air led to significant increases in fetal capillary surface area and in total and mass-specific conductances. However, the calibers of maternal blood spaces were reduced. Gestational exposure to nonfiltered air was associated with reduced volumes, calibers, and surface areas of maternal blood spaces and with greater fetal capillary surfaces and diffusive conductances. The findings indicate that urban air pollution affects placental functional morphology. Fetal weights are compromised despite attempts to improve diffusive transport across the placenta

Effect of pre- and postnatal exposure to urban air pollution on myocardial lipid peroxidation levels in adult mice

Exposure to air pollution can elicit cardiovascular health effects. Children and unborn fetuses appear to be particularly vulnerable. However, the mechanisms involved in cardiovascular damage are poorly understood. It has been suggested that the oxidative stress generated by air pollution exposure triggers tissue injury. To investigate whether prenatal exposure can enhance oxidative stress in myocardium of adult animals, mice were placed in a clean chamber (CC, filtered urban air) and in a polluted chamber (PC, Sao Paulo city) during the gestational period and/or for 3 mo after birth, according to 4 protocols: control group-prenatal and postnatal life in CC; prenatal group-prenatal in PC and postnatal life in CC; postnatal group-prenatal in CC and postnatal life in PC; and pre-post group-prenatal and postnatal life in PC. As an indicator of oxidative stress, levels of lipid peroxidation in hearts were measured by malondialdehyde (MDA) quantification and by quantification of the myocardial immunoreactivity for 15-F2t-isoprostane. Ultrastructural studies were performed to detect cellular alterations related to oxidative stress. Concentration of MDA was significantly increased in postnatal (2.45 +/- 0.84 nmol/mg) and pre-post groups (3.84 +/- 1.39 nmol/mg) compared to the control group (0.31 +/- 0.10 nmol/mg) (p < .01). MDA values in the pre-post group were significantly increased compared to the prenatal group (0.71 +/- 0.15 nmol/mg) (p = .017). Myocardial isoprostane area fraction in the pre-post group was increased compared to other groups (p <= .01). Results show that ambient levels of air pollution elicit cardiac oxidative stress in adult mice, and that gestational exposure may enhance this effect.State of Sao Paulo Research Foundation (FAPESP)Universidade de São Paulo - Laboratories of Medical Investigation (LIMs) HCFM/US

Aerobic Exercise Attenuated Bleomycin-Induced Lung Fibrosis in Th2-Dominant Mice

Introduction The aim of this study was to investigate the effect of aerobic exercise (AE) in reducing bleomycin- induced fibrosis in mice of a Th2-dominant immune background (BALB/c). Methods BALB/c mice were distributed into: sedentary, control (CON), Exercise-only (EX), sedentary, bleomycin-treated (BLEO) and bleomycin-treated+exercised (BLEO+EX);(n = 8/group). Following treadmill adaptation, 15 days following a single, oro-tracheal administration of bleomycin (1.5U/kg), AE was performed 5 days/week, 60min/day for 4 weeks at moderate intensity (60% of maximum velocity reached during a physical test) and assessed for pulmonary inflammation and remodeling, and cytokine levels in bronchoalveolar lavage (BAL). Results At 45 days post injury, compared to BLEO, BLEO+EX demonstrated reduced collagen deposition in the airways (p<0.001) and also in the lung parenchyma (p<0.001). In BAL, a decreased number of total leukocytes (p<0.01), eosinophils (p<0.001), lymphocytes (p<0.01), macrophages (p<0.01), and neutrophils (p<0.01), as well as reduced pro-inflammatory cytokines (CXCL-1;p<0.01), (IL-1 beta;p<0.001), (IL-5;p<0.01), (IL-6;p<0.001), (IL-13;p<0.01) and pro-fibrotic growth factor IGF-1 (p<0.001) were observed. Anti-inflammatory cytokine IL-10 was increased (p<0.001). Conclusion AE attenuated bleomycin-induced collagen deposition, inflammation and cytokines accumulation in the lungs of mice with a predominately Th2-background suggesting that therapeutic AE (15-44 days post injury) attenuates the pro-inflammatory, Th2 immune response and fibrosis in the bleomycin model

Aerobic Exercise Reduces Asthma Phenotype by Modulation of the Leukotriene Pathway

Submitted by Sandra Infurna ([email protected]) on 2016-12-01T11:17:20Z No. of bitstreams: 1 hugo_farianeto_etal_IOC_2016.pdf: 2748450 bytes, checksum: 98a1c02d5f24481572e9101bed50a250 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2016-12-01T11:42:37Z (GMT) No. of bitstreams: 1 hugo_farianeto_etal_IOC_2016.pdf: 2748450 bytes, checksum: 98a1c02d5f24481572e9101bed50a250 (MD5)Made available in DSpace on 2016-12-01T11:42:37Z (GMT). No. of bitstreams: 1 hugo_farianeto_etal_IOC_2016.pdf: 2748450 bytes, checksum: 98a1c02d5f24481572e9101bed50a250 (MD5) Previous issue date: 2016Nove de Julho University (UNINOVE). Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE). Laboratory of Pulmonary and Exercise Immunology (LABPEI). São Paulo, SP, Brazil.Nove de Julho University (UNINOVE). Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE). Laboratory of Pulmonary and Exercise Immunology (LABPEI). São Paulo, SP, Brazil.Nove de Julho University (UNINOVE). Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE). Laboratory of Pulmonary and Exercise Immunology (LABPEI). São Paulo, SP, Brazil.Nove de Julho University (UNINOVE). Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE). Laboratory of Pulmonary and Exercise Immunology (LABPEI). São Paulo, SP, Brazil.Nove de Julho University (UNINOVE). Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE). Laboratory of Pulmonary and Exercise Immunology (LABPEI). São Paulo, SP, Brazil.Nove de Julho University (UNINOVE). Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE). Laboratory of Pulmonary and Exercise Immunology (LABPEI). São Paulo, SP, Brazil.Nove de Julho University (UNINOVE). Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE). Laboratory of Pulmonary and Exercise Immunology (LABPEI). São Paulo, SP, Brazil.University of São Paulo (USP). School of Medicine. Laboratory of Cellular Biology (LIM59). São Paulo, SP, Brazil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.University of São Paulo (USP). School of Medicine. Laboratory of Experimental Therapeutics (LIM 20). São Paulo, SP, Brazil.University of São Paulo (USP). School of Medicine. Laboratory of Experimental Therapeutics (LIM 20). São Paulo, SP, Brazil.University of California Irvine. Institute for Memory Impairments and Neurological Disorders (MIND Institute). Irvine, CA, USA.University of São Paulo (USP). School of Medicine. Department of Pathology (LIM 05). São Paulo, SP, Brazil.University Hospital Freiburg. Department of Pneumology. COPD and Asthma Research Group. Freiburg, Germany.Nove de Julho University (UNINOVE). Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE). Laboratory of Pulmonary and Exercise Immunology (LABPEI). São Paulo, SP, Brazil.University of Tübingen. Department of Pneumology. Institute of Clinical and Experimental Transfusion Medicine (IKET). Tübingen, Germany.Nove de Julho University (UNINOVE). Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE). Laboratory of Pulmonary and Exercise Immunology (LABPEI). São Paulo, SP, Brazil.Leukotrienes (LTs) play a central role in asthma. Low- to moderate-intensity aerobic exercise (AE) reduces asthmatic inflammation in clinical studies and in experimental models. This study investigated whether AE attenuates LT pathway activation in an ovalbumin (OVA) model of asthma