Treatment of acute respiratory distress syndrome (ARDS) is challenging due to its multifactorial aetiology. The benefit of antioxidant therapy was not consistently demonstrated by previous studies. We evaluated the effect of two different doses of intravenous (i.v.) N-acetylcysteine (NAC) on oxidative stress, inflammation and lung functions in the animal model of severe LPS-induced lung injury requiring mechanical ventilation. Adult Wistar rats with LPS (500 μg/kg; 2.2 mL/kg) were treated with i.v. NAC 10 mg/kg (NAC10) or 20 mg/kg (NAC20). Controls received saline. Lung functions, lung oedema, total white blood cell (WBC) count and neutrophils count in blood and bronchoalveolar lavage fluid, and tissue damage in homogenized lung were evaluated. NAC significantly improved ventilatory parameters and oxygenation, reduced lung oedema, WBC migration and alleviated oxidative stress and inflammation. NAC20 in comparison to NAC10 was more effective in reduction of oxidative damage of lipids and proteins, and inflammation almost to the baseline. In conclusion, LPS-instilled and mechanically ventilated rats may be a suitable model of ARDS to test the treatment effects at organ, systemic, cellular and molecular levels. The results together with literary data support the potential of NAC in ARDS.

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.

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.