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(-)-Epigallocatechin-3-gallate (EGCG) is a major polyphenol of green tea that possesses a wide variety of actions. EGCG acts as a strong antioxidant which effectively scavenges reactive oxygen species (ROS), inhibits pro-oxidant enzymes including NADPH oxidase, activates antioxidant systems including superoxide dismutase, catalase, or glutathione, and reduces abundant production of nitric oxide metabolites by inducible nitric oxide synthase. ECGC also exerts potent anti-inflammatory, anti-fibrotic, pro-apoptotic, anti-tumorous, and metabolic effects via modulation of a variety of intracellular signaling cascades. Based on this knowledge, the use of EGCG could be of benefit in respiratory diseases with acute or chronic inflammatory, oxidative, and fibrotizing processes in their pathogenesis. This article reviews current information on the biological effects of EGCG in those respiratory diseases or animal models in which EGCG has been administered, i.e., acute respiratory distress syndrome, respiratory infections, COVID-19, bronchial asthma, chronic obstructive pulmonary disease, lung fibrosis, silicosis, lung cancer, pulmonary hypertension, and lung embolism, and critically discusses effectiveness of EGCG administration in these respiratory disorders. For this review, articles in English language from the PubMed database were used.

Inhalation of silica particles is an environmental and occupational cause of silicosis, a type of pneumoconiosis. Development of the lung silicosis is a unique process in which the vicious cycle of ingestion of inhaled silica particles by alveolar macrophages and their release triggers inflammation, generation of nodular lesions, and irreversible fibrosis. The pathophysiology of silicosis is complex, and interactions between the pathomechanisms have not been completely understood. However, elucidation of silica-induced inflammation cascades and inflammation-fibrosis relations has uncovered several novel possibilities of therapeutic targeting. This article reviews new information on the pathophysiology of silicosis and points out several promising treatment approaches targeting silicosis-related pathways.

Lung silicosis is a serious pulmonary disease caused by an exposure of lung to inhaled silicon dioxide (SiO2) or silica. Although pathomechanisms of the disease have not been fully elucidated, oxidative stress has been recognized as a fundamental factor triggering a fibrotizing inflammation leading to irreversible changes in lung tissue. Based on this knowledge, therapeutic potential of various antioxidants has been intensively discussed. Among them, N-acetylcysteine with its multiple anti-inflammatory and antioxidant actions and a long-term experience with its clinical use in various diseases appears as a very promising choice. The purpose of this article is to review the therapeutic effects of N-acetylcysteine particularly in relation to a lung injury and to point out a potential of N-acetylcysteine in the treatment of lung silicosis.

Pulmonary fibrosis, represented mainly by idiopathic pulmonary fibrosis, develops chronic and progressive changes in lung parenchyma with high mortality and limited therapeutic options. The aim of this review was to summarize the most common experimental models used in the research of pulmonary fibrosis. Lung damage associated with development of pulmonary fibrosis can be caused by irradiation or by instillation of bleomycin, fluorescein isothiocyanate (FITC), silicon dioxide (silica), asbestos, etc. This article reviews the characteristics of the most frequently used animal models of fibrosis, including the limitations of their use. Although none of the used animal models resembles completely the changes in human pulmonary fibrosis, similarities between them allow preclinical testing of novel treatment approaches or their combinations in the laboratory conditions before their use in the clinical practice.

Lung silicosis is primarily caused by inhalation of particles of silicon oxide (silica). Despite a huge progress in understanding the interactions among the pathomechanisms of lung silicosis in the last years, there is a lack of effective therapy. With respect to a wide therapeutic action of corticosteroids, the purpose of this pilot study was to evaluate early effects of dexamethasone on several markers of inflammation and lung fibrosis in a rat model of silicosis. The silicosis model was induced by a single transoral intratracheal instillation of silica (50 mg/ml/animal), while the controls received an equivalent volume of sterile saline. The treatment with intraperitoneal dexamethasone initiated the next day after the silica instillation and was given 2-times a week at a dose of 1 mg/kg, while the controls received an equivalent volume of saline. The animals were euthanized 14 or 28 days after the treatment onset. Total and differential counts of leukocytes in the blood and bronchoalveolar lavage (BAL) fluid were determined. The presence of collagen in the bronchioles and lung vessels was detected by Sirius red staining and a smooth muscle mass was detected by smooth muscle actin. In comparison to saline, the instillation of silica increased the total count of circulating leukocytes after 14 and 28 days of the experiment (both p<0.05), which was associated with higher counts of lymphocytes (p<0.05 after 14 days, p>0.05 after 28 days) and slight but non-significant increases in neutrophils and eosinophils (both p>0.05). Although the total cell count in the BAL fluid did not change significantly, the percentages and absolute counts of neutrophils, eosinophils, and lymphocytes (p<0.05, p<0.01 or p<0.001) elevated after 14 and 28 days of the experiment. Silica induced an accumulation of collagen in the bronchioles (p<0.001 after both 14 and 28 days) and pulmonary vessels (p<0.01 after both 14 and 28 days) and elevated a formation of smooth muscle mass (p<0.05 after 14 days, p<0.01 or p<0.001 after 28 days). Treatment with dexamethasone decreased circulating leukocytes (p<0.01) and lymphocytes (p<0.001) and increased neutrophils (p<0.05), which was associated with a slightly decreased total cell count in BAL (p>0.05), decline in lymphocytes (p<0.01), and slight decreases in neutrophils and eosinophils after 28 days of the treatment. Moreover, dexamethasone reduced the accumulation of collagen (p<0.01 after 14 days and p<0.001 after 28 days) and the formation of smooth muscle mass (p<0.01 for bronchioles and p>0.05 for vessels after 24 days, p<0.001 for both bronchioles and vessels after 28 days). In conclusion, early dexamethasone treatment mitigated silica-induced granulocytic-lymphocytic inflammation and decreased a formation of collagen and smooth muscle mass in the bronchiolar and vascular walls, demonstrating a therapeutic potential of dexamethasone in the lung silicosis.

Herbal compounds including those already well-established in traditional Chinese medicine have been increasingly tested in the treatment of various diseases. Recent studies have shown that herbal compounds can be of benefit also for pulmonary silicosis as they can diminish changes associated with silica-induced inflammation, fibrosis, and oxidative stress. Due to a lack of effective therapeutic strategies, development of novel approaches which may be introduced particularly in the early stage of the disease, is urgently needed. This review summarizes positive effects of several alternative plant-based drugs in the models of experimental silicosis with a potential for subsequent clinical investigation and use in future.

Inhalation of silica particles causes inflammatory changes leading to fibrotizing silicosis. Considering a lack of effective therapy, and a growing information on the wide actions of green tea polyphenols, particularly epigallocatechin-3-gallate (EGCG), the aim of this study was to evaluate the early effects of EGCG on markers of inflammation and lung fibrosis in silicotic rats. The silicosis model was induced by a single transoral intratracheal instillation of silica (50 mg/mL/animal), while controls received an equivalent volume of saline. The treatment with intraperitoneal EGCG (20 mg/kg, or saline in controls) was initiated the next day after silica instillation and was given twice a week. Animals were euthanized 14 or 28 days after the treatment onset, and the total and differential counts of leukocytes in the blood and bronchoalveolar lavage fluid (BALF), wet/dry lung weight ratio, and markers of inflammation, oxidative stress, and fibrosis in the lung were determined. The presence of collagen and smooth muscle mass in the walls of bronchioles and lung vessels was investigated immunohistochemically. Early treatment with EGCG showed some potential to alleviate inflammation, and a trend to decrease oxidative stress-induced changes, including apoptosis, and a prevention of fibrotic changes in the bronchioles and pulmonary vessels. However, further investigations should be undertaken to elucidate the effects of EGCG in the lung silicosis model in more detail. In addition, because of insufficient data from EGCG delivery in silicosis, the positive and eventual adverse effects of this herbal compound should be carefully studied before any preventive use or therapy with EGCG may be recommended.

Sex seems to be a contributing factor in the pathogenesis of bronchial asthma. This study aimed to find sex-related differences in metabolome measured by hydrogen-1 nuclear magnetic resonance (1H NMR) spectroscopy in healthy and ovalbumin (OVA)-sensitized guinea pigs. Adult male and female animals were divided into controls and OVA-sensitized groups. OVA-sensitization was performed by OVA systemic and inhalational administration within 14 days; on day 15, animals were killed by anesthetic overdose followed by exsanguination. Blood was taken and differential white blood cell count was measured. Left lung was saline-lavaged and differential cell count in the bronchoalveolar lavage fluid (BALF) was measured. After blood centrifugation, plasma was processed for 1H NMR analysis. Metabolomic data was evaluated by principal component analysis (PCA). Eosinophil counts elevated in the BALF confirming eosinophil-mediated inflammation in OVA-sensitized animals of both sexes. Sex differences for lactate, glucose, and citrate were found in controls, where these parameters were lower in males than in females. In OVA-sensitized males higher glucose and lower pyruvate were found compared to controls. OVA-sensitized females showed lower lactate, glucose, alanine, 3-hydroxy-butyrate, creatine, pyruvate, and succinate concentrations compared to controls. In OVA-sensitized animals, lactate concentration was lower in males. Data from females (healthy and OVA-sensitized) were generally more heterogeneous. Significant sex differences in plasma concentrations of metabolites were found in both healthy and OVA-sensitized animals suggesting that sex may influence the metabolism and may thereby contribute to different clinical picture of asthma in males and females.

(-)-Epigallocatechin-3-gallate (EGCG) is a major polyphenol of green tea that possesses a wide variety of actions. EGCG acts as a strong antioxidant which effectively scavenges reactive oxygen species (ROS), inhibits pro-oxidant enzymes including NADPH oxidase, activates antioxidant systems including superoxide dismutase, catalase, or glutathione, and reduces abundant production of nitric oxide metabolites by inducible nitric oxide synthase. ECGC also exerts potent anti-inflammatory, anti-fibrotic, pro-apoptotic, anti-tumorous, and metabolic effects via modulation of a variety of intracellular signaling cascades. Based on this knowledge, the use of EGCG could be of benefit in respiratory diseases with acute or chronic inflammatory, oxidative, and fibrotizing processes in their pathogenesis. This article reviews current information on the biological effects of EGCG in those respiratory diseases or animal models in which EGCG has been administered, i.e., acute respiratory distress syndrome, respiratory infections, COVID-19, bronchial asthma, chronic obstructive pulmonary disease, lung fibrosis, silicosis, lung cancer, pulmonary hypertension, and lung embolism, and critically discusses effectiveness of EGCG administration in these respiratory disorders. For this review, articles in English language from the PubMed database were used.