Experimental Asbestosis Research Articles

LESIONAL ASPECTS IN RAT EXPERIMENTAL ASBESTOSIS

Asbestos is a professional diseases related to various injuries including inflammation, fibrosis, even malignancy. The purpose of present paper was to reveal the gross and histological aspects occurring in rat experimental asbestosis. The experiment was carried out 240 days long, on Wistar rats, intraperitoneally injected once with aqueous asbestos suspension. In the end, animals were euthanasiated by prolonged narcosis. Necropsy was done and tissue samples were harvested from both affected and apparently healthy areas. A haematoxylin-eosin and Tricrom Masson staining was made from each sample. The slides were object to minutely examination. Gross evaluation revealed various size granulomas in various locations. Adherence among serous membranes and abdominal organs were also found. Histologically, granulomas, regardless of location, revealed in central area asbestos fibers, fagocytated or not, covered mainly by fibroblasts, capillaries and connective tissue. Those aspects reveal strictly fibroblastic and fibrotic proliferation. However, undifferentiated cell nests and abnormal mitotic figures were found; this cell nests might be developing points for malignant proliferation.

Expression of antioxidant enzymes in rat lungs after inhalation of asbestos or silica.

Several studies indicate that active oxygen species play an important role in the development of pulmonary disease (asbestosis and silicosis) after exposure to mineral dust. The present study was conducted to determine if inhaled fibrogenic minerals induced changes in gene expression and activities of antioxidant enzymes (AOE) in rat lung. Two different fibrogenic minerals were compared, crocidolite, an amphibole asbestos fiber, and cristobalite, a crystalline silicon dioxide particle. Steady-state mRNA levels, immunoreactive protein, and activities of selected AOE were measured in lungs 1-10 days after initiation of exposure and at 14 days after cessation of a 10-day exposure period. Exposure to asbestos resulted in significant increases in steady-state mRNA levels of manganese-containing superoxide dismutase (MnSOD) at 3 and 9 days and of glutathione peroxidase at 6 and 9 days. An increase in steady-state mRNA levels of copper, zinc-containing superoxide dismutase (CuZnSOD), was observed at 6 days. Exposure to asbestos also resulted in overall increased enzyme activities of catalase, glutathione peroxidase and total superoxide dismutase in lung. In contrast, silica caused a dramatic increase in steady-state levels of MnSOD mRNA at all time periods and an increase in glutathione peroxidase mRNA levels at 9 days. Activities of AOE remained unchanged in silica-exposed lungs. In both models, increases in gene expression of MnSOD correlated with increased amounts of MnSOD immunoreactive protein in lung and the pattern and extent of inflammation. These data indicate that the profiles of AOE are dissimilar during the development of experimental asbestosis or silicosis and suggest different mechanisms of lung defense in response to these minerals.

Contributions of Experimental Asbestosis in Sheep to the Understanding of Asbestosisa

Contributions of Experimental Asbestosis in Sheep to the Understanding of Asbestosis^a

Effects of cyclophosphamide treatment in experimental asbestosis.

The potential role of immunosuppressive therapy in asbestosis was evaluated in the sheep model of experimental asbestosis. A diffuse peribronchiolar alveolar and interstitial fibrosing alveolitis was developed in 10 animals following 2 years of exposure consisting of slow intratracheal infusion of 100 mg Canadian chrysotile in 100 ml saline every 2 weeks. A control group of 10 sheep concomitantly receiving only 100 ml saline intratracheally was also enrolled in the study. One group of 5 control sheep and one group of 5 asbestosis sheep received 1 mg/kg cyclophosphamide in 10 ml saline iv every 2 weeks, the other 10 sheep receiving only saline. One year after beginning of therapy, survival rates were comparable in the 2 control groups and the asbestosis group without therapy at 80%, whereas it was significantly reduced at 20% in the asbestosis group with therapy. Deaths in the latter were associated with significant increase in peripheral blood and lung lavage neutrophils, increased intensity of fibrosing alveolitis, worsening of lung functions, and worsening in the radiographic diffuse lung opacities. This was documented on histopathology to be associated with more intense fibrotic disease and bacterial pneumonia in the group of sheep with asbestosis receiving the immunosuppressor drug. We conclude that cyclophosphamide therapy in experimental asbestosis accelerated the fibrotic process and reduced significantly the survival rate of the animals.

Elevated histamine content of lung lavage in human asbestosis.

Increased histamine levels in lung lavage have been previously reported in humans with idiopathic fibrosing alveolitis and mast cell proliferation was documented on lung tissue. Similarly, mast cell proliferation has been documented in experimental asbestosis. To evaluate the relevance of these observations to human asbestosis, we performed bronchoalveolar lavage in 10 normal volunteers (group N) and 22 long-term asbestos workers from the mines and mills of Quebec. The 22 asbestos workers were evaluated by standard clinical, functional, radiographic, and gallium-67 lung uptake tests. Five did not have any abnormality suggestive of asbestosis and constituted group A. The 6 in group B were without sufficient criteria for well-established asbestosis, but their lung pressure-volume curve was rigid and67Ga lung uptake was increased; the 11 in group C had well-established asbestosis. In addition to standard parameters of BAL cellularity and biochemistry, we measured histamine levels by fluorometric method. In normals, histamine levels were 1.0 ± 0.3 ng/ml, in group A 1.25 ± 0.37 ng/ml (NS), in group B 2.26 ± 0.86 ng/ml (P < 0.05 B vs A or N), and in group C it was 2.65 ± 0.44 ng/ml (P < 0.05 C vs A or N). BAL eosinophils were absent in normals and group A, 272 ± 136/ml in group B, and 764 ± 350 in group C (P < 0.05 for groups B and C vs normals and group A), but did not correlate with histamine content of BAL. This study provides evidence of an elevated content of histamine in the bronchoalveolar milieu of patients with early and late asbestosis. This finding is of interest in relation to the potential role of the mast cell in the disease process.

Pulmonary bombesin in experimentally induced asbestosis in rats.

The pulmonary levels of immunoreactive bombesin in normal rat lungs and rat lungs exposed to asbestos were determined. Experimental asbestosis was induced in rats by a single intratracheal injection of 5 mg or 10 mg UICC standard Canadian Chrysotile B while sham-operated control rats received only the saline carrier. At 1, 3, 6, and 9 months following instillation, 5 animals of each group were sacrificed and the lungs removed. A section was kept for morphologic analysis, while the remaining portion was submitted to acid extraction and later measured for bombesin content by radioimmunoassay (RIA). The Chrysotile B-exposed tissues displayed the characteristic features typical of the fibrotic state associated with asbestosis one month following exposure and thereafter. The pulmonary bombesinlike immunoreactivity ranged from 4.5-7.5 pmoles/g tissue in normal rat lung, and these levels remained unchanged at 1 and 3 months after asbestos exposure. However at 6 and 9 months, significant increases ranging between 2 and 2.5 fold were observed. The initial increases in bombesin levels occurred at a later time (6 months) than those already observed for vasoactive intestinal peptide (VIP) (3 months). However, VIP levels plateaued at 9 months, while those of bombesin were still increasing. High-pressure liquid chromatography (HPLC) coupled with RIA demonstrates the presence of two bombesin-immunoreactive peaks in normal rat lung, the major one coeluting with the mammalian bombesinlike peptide gastrin-releasing peptide (GRP) and the other one being presumably a C-terminal portion of GRP. These data indicate that immunoreactive bombesin and VIP are selectively increased at different times following asbestos instillation and that these changes occur after the onset of fibrosis and the appearance of well-defined fibrotic lesions.

A pathological study on the pulmonary fibrosing process in experimental asbestosis

A pathological study on the pulmonary fibrosing process in experimental asbestosis

Biochemical Components of Bronchoalveolar Lavage in Early Experimental Asbestosis of the Sheep: Phospholipase A 2 Activity, Prostaglandin E 2 and Proteins

Biochemical Components of Bronchoalveolar Lavage in Early Experimental Asbestosis of the Sheep: Phospholipase A 2 Activity, Prostaglandin E 2 and Proteins

Biochemical components of bronchoalveolar lavage in early experimental asbestosis of the sheep: phospholipase A2 activity, prostaglandin E2 and proteins.

Biochemical analyses of bronchoalveolar lavage (BAL) supernatants of sheep treated with weekly intratracheal instillations (for 6 months) of saline, 2 mg, or 128 mg of asbestos (chrysotile B; UICC) were performed. Our results showed that proteins (either total or its various components) and phospholipase A2 activity were unchanged in the low exposure group as compared to controls. However, in the high exposure group, with histopathological evidence of early asbestosis, there were significant increases in total proteins, albumin, alpha 2-globulin, beta- and gamma-globulins as well as phospholipase A2 activity of BAL fluid. Prostaglandin E2 activity was significantly increased in both low and high dose groups. These changes in protein and lipid components of BAL following asbestos exposure constitute early indices of lung inflammatory reactions which may contribute to the development of asbestosis.

Effect of BCG on experimental asbestosis.

Chrysotile inoculated intratracheally into normal and BCG immunised guinea pigs incited a macrophage response and reticulin fibrosis. The immunised animals showed a more rapid localisation of pulmonary lesions and disappearance of the chrysotile fibres leading to accelerated focal fibrosis. More rapid transport of chrysotile to the lymph nodes of immunised animals was also observed. These findings suggest that BCG vaccine can influence the development of pathological lesions of asbestosis in guinea pigs by inducing them earlier and more rapidly.

Experimental asbestosis: an investigation of functional and pathological disturbances. I. Methods, control animals and exposure conditions.

The measurement of respiratory function and quantitative assessment of changes in lung morphology are described in a long-term study of asbestos-exposed guinea pigs. Resistance and dynamic compliance of the guinea pig respiratory system were measured non-destructively, and the tidal volume and rate of spontaneous breathing were also determined. A point counting technique was used with histological preparations to quantify morphological changes. In one group of control animals, investigated between 3 and 28 months of age, dynamic compliance and tidal volume tended to increase, but resistance and breathing rate tended to decrease, as the animals matured. In contrast the percentage by volume of various lung components remained constant throughout this period. The animals were exposed to chrysotile and amosite aerosols, both aerosols containing high concentrations of short fibres (less than 5 micrometer) and at least 1000 fibres/ml longer than 5 micrometer. The total fibre concentration during chrysotile exposure was probably at least double that during amosite exposure. A gradient of fibre concentration (less than 5 micrometer) was detected along the exposure chamber, but this gradient was not reflected in the respiratory function of animals exposed at different positions along the chamber. These findings are discussed in relation to possible dose-dependence of the response.

Experimental asbestosis: an investigation of functional and pathological disturbances. II. Results for chrysotile and amosite exposures.

<b>Objective:</b> This study assessed renters’ preferences for official smoking policies in their buildings and their practices concerning restricting tobacco smoking in their apartments. <b>Design:</b> Renters (n = 301) living in large apartment complexes in a suburb of Minneapolis, Minnesota, completed a mail survey. <b>Main outcome measures:</b> The survey asked about the official smoking policies in place in their apartment buildings, their preferences for policies, whether they had smelled tobacco smoke coming into their apartments from without, and, if so, what they had done about it. <b>Results:</b> The majority of non-smokers (79%) preferred that their building be smoke-free. When asked to identify the current smoking policy in their buildings, residents disagreed substantially. Most renters (60%) reported smoke-free policies in their own apartments and another significant proportion (23%) restricted smoking to certain areas or occasions or persons. 75% thought that enforcing a smoke-free policy for guests would not be difficult. 53% of those in non-smoking households had smelled tobacco smoke in their apartments; most of these reported being bothered by it. However, very few complained to the building owner or manager (15.5%) or to the smoker (6.9%). <b>Conclusions:</b> The majority of non-smokers preferred that their buildings be smoke-free. A failure to report problems to apartment managers might be an impediment to instituting smoke-free policies in apartment buildings. The considerable disagreement among residents within apartment complexes about the current official smoking policy in their buildings suggests that policies are lacking or are not well communicated.

Biochemical changes in serim of guinea pigs in experimental asbestosis

Biochemical changes in serim of guinea pigs in experimental asbestosis

Experimental asbestosis in rats The effect of particle size and of added alumina.

Experimental asbestosis in rats The effect of particle size and of added alumina.