RESUMO
Acute and chronic lung injuries are among the leading causes of mortality worldwide. Lung injury can affect several components of the respiratory system, including the airways, parenchyma, and pulmonary vasculature. Although acute and chronic lung injuries represent an enormous economic and clinical burden, currently available therapies primarily focus on alleviating disease symptoms rather than reversing and/or preventing lung pathology. Moreover, some supportive interventions, such as oxygen and mechanical ventilation, can lead to (further) deterioration of lung function and even the development of permanent injuries. Lastly, sepsis, which can originate extrapulmonary or in the respiratory system itself, contributes to many cases of lung-associated deaths. Considering these challenges, we aim to summarize molecular and cellular mechanisms, with a particular focus on airway inflammation and oxidative stress that lead to the characteristic pathophysiology of acute and chronic lung injuries. In addition, we will highlight the limitations of current therapeutic strategies and explore new antioxidant-based drug options that could potentially be effective in managing acute and chronic lung injuries.
RESUMO
Inhalation of harmful particles appears as a primary factor for the onset and establishment of chronic obstructive pulmonary disease (COPD). Cigarette smoke acutely promotes an exacerbated inflammatory response with oxidative stress induction with DNA damage. Administration of Gold Nanoparticles (GNPs) with 20 nm in different concentrations can revert damages caused by external aggravations. The effects of GNPs in a COPD process have not been observed until now. The objective of this work was to evaluate the therapeutic effects of intranasal administration of different doses of GNPs after acute exposure to industrial cigarette smoke. Thirty male Swiss mice were randomly divided into five groups: Sham; cigarette smoke (CS); CS + GNPs 2.5 mg/L; CS + GNPs 7.5 mg/L and CS + GNPs 22.5 mg/L. The animals were exposed to the commercial cigarette with filter in an acrylic inhalation chamber and treated with intranasal GNPs for five consecutive days. The results demonstrate that exposure to CS causes an increase in inflammatory cytokines, histological changes, oxidative and nitrosive damage in the lung, as well as increased damage to the DNA of liver cells, blood plasma and lung. Among the three doses of GNPs (2.5, 7.5, and 22.5 mg/L) used, the highest dose had better anti-inflammatory effects. However, GNPs at a dose of 7.5 mg/L showed better efficacies in reducing ROS formation, alveolar diameter, and the number of inflammatory cells in histology, in addition to significantly reduced rate of DNA damage in lung cells without additional systemic genotoxicity already caused by cigarette smoke.
Assuntos
Fumar Cigarros , Nanopartículas Metálicas , Doença Pulmonar Obstrutiva Crônica , Administração Intranasal , Animais , Líquido da Lavagem Broncoalveolar , Ouro/farmacologia , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/patologia , NicotianaRESUMO
This study aimed to verify possible alterations involving histological and oxidative stress parameters in the lungs of wild bats in the Carboniferous Basin of Santa Catarina (CBSC) state, Southern Brazil, as a means to evaluate the impact of coal dust on the health of wildlife. Specimens of frugivorous bat species Artibeus lituratus and Sturnira lilium were collected from an area free of coal dust contamination and from coal mining areas. Chemical composition, histological parameters, synthesis of oxidants and antioxidant enzymes, and oxidative damage in the lungs of bats were analyzed. Levels of Na, Cl, Cu, and Br were higher in both species collected in the CBSC than in the controls. Levels of K and Rb were higher in A. lituratus, and levels of Si, Ca, and Fe were higher in S. lilium collected in the carboniferous basin. Both bat species inhabiting the CBSC areas exhibited an increase in the degree of pulmonary emphysema compared to their counterparts collected from control areas. Sturnira lilium showed increased reactive oxygen species (ROS) and 2',7'-dichlorofluorescein (DCF) levels, while A. lituratus showed a significant decrease in nitrite levels in the CBSC samples. Superoxide dismutase (SOD) activity did not change significantly; however, the activity of catalase (CAT) and levels of glutathione (GSH) decreased in the A. lituratus group from CBSC compared to those in the controls. There were no differences in NAD(P)H quinone dehydrogenase 1 protein (NQO1) abundance or nitrotyrosine expression among the different groups of bats. Total thiol levels showed a significant reduction in A. lituratus from CBSC, while the amount of malondialdehyde (MDA) was higher in both A. lituratus and S. lilium groups from coal mining areas. Our results suggested that bats, especially A. lituratus, living in the CBSC could be used as sentinel species for harmful effects of coal dust on the lungs.
Assuntos
Quirópteros , Minas de Carvão , Carvão Mineral/toxicidade , Pulmão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Brasil , Catalase/metabolismo , Quirópteros/anatomia & histologia , Quirópteros/metabolismo , Poeira , Glutationa/metabolismo , Pulmão/anatomia & histologia , Pulmão/química , Pulmão/metabolismo , Malondialdeído/metabolismo , Metais/análise , Modelos Biológicos , Enfisema Pulmonar/veterinária , Espécies Reativas de Oxigênio/metabolismoRESUMO
Studies have shown the benefits of gold nanoparticles (GNPs) in muscle and epithelial injury models. In physiotherapy, the use of the microcurrent apparatus is associated with certain drugs (Iontophoresis) to increase the topical penetration and to associate the effects of both therapies. Therefore, the objective of this study was to investigate the effects of iontophoresis along with GNPs in the skeletal muscle of rats exposed to a traumatic muscle injury. We utilised 50 Wistar rats randomly divided in to five experimental groups (n = 10): Control group (CG); Muscle injury group (MI); MI + GNPs (20 nm, 30 mg kg-1); MI + Microcurrent (300 µA); and MI + Microcurrent + GNPs. The treatment was performed daily for 7 days, with the first session starting at 24 h after the muscle injury. The animals were sacrificed and the gastrocnemius muscle was surgically removedand stored for the proper evaluations. The group that received iontophoresis with GNPs showed significant differences in inflammation and oxidative stress parameters and in the histopathological evaluation showed preserved morphology. In addition, we observed an improvement in the locomotor response and pain symptoms of these animals. These results suggest that the association of boththerapies accelerates the inflammatory response of the injured limb.
Assuntos
Ouro/química , Iontoforese/métodos , Nanopartículas Metálicas/administração & dosagem , Músculo Esquelético/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Inflamação/patologia , Masculino , Músculo Esquelético/lesões , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
Duchenne muscular dystrophy (DMD) is an X-linked recessive hereditary myopathy characterised by progressive muscle degeneration in male children. As a consequence of DMD, increased inflammation and oxidative stress occur in muscle tissue along with morphological changes. Several studies have reported anti-inflammatory and antioxidant effects of gold nanoparticles (GNP) in muscle injury models. The objective of this study was to evaluate these effects along with the impacts of the disease on histopathological changes following chronic administration of GNP to Mdx mice. Two-month-old Mdx mice were separated into five groups of eight individuals each, as follows: wild-type (WT), Mdx-modified without treatment, Mdx + 2.5 mg/kg GNP, Mdx + 7.0 mg/kg GNP and Mdx + 21 mg/kg GNP. GNP with a mean diameter of 20 nm were injected subcutaneously at concentrations of 2.5, 7.0 and 21 mg/kg. Treatments continued for 30 d with injections administered at 48-h intervals. Twenty-four hours after the last injection, the animals were killed and the central region of the gastrocnemius muscle was surgically removed. Chronic administration of GNP reduced inflammation in the gastrocnemius muscle of Mdx mice and reduced morphological alterations due to inflammatory responses to muscular dystrophy. In addition, GNP also demonstrated antioxidant potential by reducing the production of reactive oxygen and nitrogen species, reducing oxidative damage and improving antioxidant activity.
Assuntos
Ouro/farmacologia , Mediadores da Inflamação/metabolismo , Nanopartículas Metálicas/química , Estresse Oxidativo/efeitos dos fármacos , Animais , Biomarcadores , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Inflamação/tratamento farmacológico , Camundongos , Camundongos Endogâmicos mdx , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Distrofia Muscular de Duchenne/patologia , Espécies Reativas de Nitrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
The bacterial lipopolysaccharide (LPS) is a highly toxic molecule derived from the outer membrane of gram-negative bacteria. LPS endotoxin affects the lungs and is used as a model of acute pulmonary inflammation affecting the cellular morphology of the organ. Previously, gold nanoparticles (GNPs) have been shown to demonstrate anti-inflammatory and antioxidative activity in muscle and epithelial injury models. The objective of this study was to investigate the effect of the intraperitoneal treatment using GNPs on the inflammatory response and pulmonary oxidative stress induced by LPS. Wistar rats were divided into four groups (N = 10): Sham; Sham + GNPs 2.5 mg/kg; LPS; and LPS + GNPs 2.5 mg/kg. Treatment with LPS upregulated the levels of markers of cellular and hepatic damage (CK, LDH, AST, and alanine aminotransferase); however, the group treated with only GNPs exhibited no toxicity. Treatment with GNPs reversed LPS-induced changes with respect to total peritoneal leukocyte count and the pulmonary levels of pro-inflammatory cytokines (IFN-γ and IL-6). Histological analysis revealed that treatment with GNPs reversed the increase in alveolar septum thickness due to LPS-induced fibrosis. In addition, treatment with GNPs decreased production of oxidants (nitrite and DCFH), reduced oxidative damage (carbonyl and sulfhydryl), and downregulated activities of superoxide dismutase and catalase. Treatment with GNPs did not showed toxicity; however, it exhibited anti-inflammatory and antioxidative activity that reversed morphological alterations induced by LPS.
Assuntos
Ouro/uso terapêutico , Nanopartículas Metálicas/uso terapêutico , Pneumonia/patologia , Pneumonia/terapia , Doença Aguda , Animais , Antioxidantes/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos , Pulmão/patologia , Masculino , Nanopartículas Metálicas/ultraestrutura , Estresse Oxidativo , Pneumonia/enzimologia , Ratos Wistar , Espectrofotometria UltravioletaRESUMO
The present study sought to evaluate the effects of physical training on histological parameters and oxidative stress in the myocardium of mice chronically exposed to hand-rolled cornhusk cigarette (HRCC) smoke. Male Swiss mice (60 days old, 30-35â¯g) were either exposed to ambient air or passively exposed to the smoke of 12 cigarettes daily over 3 sessions (4 cigarettes per session) for 60 consecutive days with or without physical training for 8 weeks. Forty-eight hours after the last training session, the heart was surgically removed for histological analysis and measurement of oxidative stress parameters. Histological imaging revealed cell disruption, with poorly defined nuclei, in the mice exposed to HRCC smoke, but not in the control group. However, mice exposed to HRCC smoke with physical training displayed signs of tissue repair and improved tissue integrity. Biochemical analysis revealed decreased production of superoxide, 2',7'-dichlorofluorescein (DCF), and nitrite, as well as decreased protein carbonylation, in the physical training groups, likely due to the exercise-induced increase in glutathione peroxidase (GPX) activity and glutathione (GSH) content. Taken together, our results suggest that physical exercise exerts cardioprotective effects by modulating the redox responses in animals exposed to HRCC smoke.
Assuntos
Glutationa Peroxidase/metabolismo , Glutationa/metabolismo , Miocárdio/metabolismo , Condicionamento Físico Animal , Carbonilação Proteica , Fumar/metabolismo , Animais , Masculino , Camundongos , Miocárdio/patologia , Fumar/patologiaRESUMO
Asthma is an allergic inflammation driven by the Th2 immune response with release of cytokines such as IL-4 and IL-13, which contribute to the airflow limitations and airway hyperresponsiveness (AHR). The involvement of oxidative stress in this process is well-established, but the specific role of the superoxide anion and nitric oxide in asthma are poorly understood. Thus, the aim of this study was to investigate the mechanisms underlying the superoxide anion/nitric oxide production and detoxification in a murine asthma model. BALB/c male mice were sensitised and challenged with ovalbumin (OVA). Pretreatments with either apocynin (14 mg/kg) or allopurinol (25 mg/kg) (superoxide anion synthesis inhibitors), aminoguanidine (50 mg/kg) (nitric oxide synthesis inhibitor) or diethyldithiocarbamate (100 mg/kg) (superoxide dismutase inhibitor) were performed 1 h before the challenge. Our data showed that apocynin and allopurinol ameliorated AHR and reduced eosinophil peroxidase, as well as IL-4 and IL-13 levels. Apocynin also abrogated leukocyte peribronchiolar infiltrate and increased IL-1ß secretion. Aminoguanidine preserved lung function and shifted the Th2 to the Th1 response with a reduction of IL-4 and IL-13 and increase in IL-1ß production. Diethyldithiocarbamate prevented neither allergen-induced AHR nor eosinophil peroxidase (EPO) generation. All treatments protected against oxidative damage observed by a reduction in TBARS levels. Taken together, these results suggest that AHR in an asthma model can be avoided by the down-regulation of superoxide anion and nitric oxide synthesis in a mechanism that is independent of a redox response. This down-regulation is also associated with a transition in the typical immunological Th2 response toward the Th1 profile.
Assuntos
Asma/imunologia , Inflamação/imunologia , Óxido Nítrico/antagonistas & inibidores , Hipersensibilidade Respiratória/imunologia , Superóxidos/antagonistas & inibidores , Acetofenonas/administração & dosagem , Alopurinol/administração & dosagem , Animais , Asma/metabolismo , Asma/patologia , Modelos Animais de Doenças , Peroxidase de Eosinófilo/imunologia , Peroxidase de Eosinófilo/metabolismo , Guanidinas/administração & dosagem , Humanos , Hipersensibilidade/imunologia , Hipersensibilidade/metabolismo , Hipersensibilidade/patologia , Inflamação/metabolismo , Inflamação/patologia , Interleucina-13/imunologia , Interleucina-13/metabolismo , Interleucina-1beta/imunologia , Interleucina-1beta/metabolismo , Interleucina-4/imunologia , Interleucina-4/metabolismo , Camundongos , Óxido Nítrico/imunologia , Ovalbumina/imunologia , Estresse Oxidativo/imunologia , Espécies Reativas de Oxigênio/imunologia , Espécies Reativas de Oxigênio/metabolismo , Hipersensibilidade Respiratória/metabolismo , Hipersensibilidade Respiratória/patologia , Superóxidos/imunologia , Células Th1/imunologia , Células Th2/imunologiaRESUMO
Gold nanoparticles (GNPs) have antioxidant and anti-inflammatory effects. However, toxicity is still a concern; therefore, it is critical to study both the therapeutic and toxic properties of GNPs. In this study, we evaluated the effects of the intraperitoneal administration of GNPs (20nm, at a concentration of 2.5mg/L for 21days) every 24 or 48h on oxidative stress, antioxidant status, and electron chain transport (ETC) in the brain. Liver histology and blood marker analyses were conducted to establish a time routine of GNP administration. The concentrations of GNP in the brain and liver were similar. Hepatic and serum levels of cholesterol, triglycerides, and transaminases were not altered after the administration of GNP every 24 or 48h. The superoxide and nitric oxide levels were unchanged after administration of GNP. Dichlorodihydrofluorescein (DCFH) levels decreased after the administration of GNP every 48h compared with that in the saline group. Sulfhydryl and carbonyl levels, as well as superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and glutathione (GSH) activities were not altered in the brain after administration of GNP in the two time periods studied. The GNP 48h group showed increased brain ETC activity. Compared to that in the saline group, the GNP 24h group showed marked parenchyma changes with cell necrosis and leukocyte infiltration. We therefore suggest that a concentration of 2.5mg/L of GNP administered every 48h has potential therapeutic benefits without toxicity.
Assuntos
Nanopartículas Metálicas , Animais , Antioxidantes , Catalase , Glutationa , Glutationa Peroxidase , Ouro , Estresse Oxidativo , Ratos , Ratos WistarRESUMO
Ovalbumin-induced allergic lung inflammation (ALI) is a condition believed to be mediated by cytokines, extracellular matrix remodeling, and redox imbalance. In this study, we evaluated pulmonary function together with inflammatory markers as interleukin-4 (IL-4), myeloperoxidase (MPO), eosinophil cells, and redox markers in the lungs of BALB/c mice after ovalbumin (OVA) sensitization and challenge. Our results showed an increase in bronchial hyperresponsiveness stimulated by methacholine (Mch), inflammatory cell influx, especially eosinophils together with an increase of high mobility group box 1 (HMGB1) and altered lipid peroxidation (LP) and antioxidant defenses in the OVA group compared to the control group (p ≤ 0.5). Thus, we demonstrated that OVA-induced ALI altered redox status concomitantly with impaired lung function, which was associated with HMGB1 expression and proteolytic remodeling. Taken together all results found here, we may suggest HMGB1 is an important therapeutic target for asthma, once orchestrates the redox signaling, inflammation, and remodeling that contribute to the disease development.