Experimental Lung Silicosis

In 57 silicotic and 44 control rats, functional, biochemical, and histological measurements of the lungs were performed during four months of developing silicosis. Pulmonary silicosis was produced by a single intratracheal injection of 50 mg of quartz dust. Among the earliest changes were a significant decrease in arterial oxygen partial pressure, a decrease in lung compliance, and an increase of thoracic gas volume one month after dusting. These were accompanied by corresponding changes in lung weight, in hydroxyprolfne content, and in the histological appearance of the lungs. Four months after dusting the silicotic rate differed significantly in all measured factors from the controls. The picture of fully developed functional, biochemical, and morphological changes In rat silicosis was identical with that described earlier.     

Unilateral Pulmonary Function Study of Ozone Toxicity in Rabbits

In a unilateral pulmonary function study, Flemish giant rabbits breathing 12 ± 1 ppm ozone in the left lung exhibited an initial bilateral increase in respiratory rate and minute volume as well as a bilateral decrease in tidal volume and dynamic compliance. Pulmonary function parameters were not statistically different for ozone- and ambient-airtreated lungs until pulmonary edema developed in the lung exposed to ozone, as evidenced by a percent increase in the wet weight of that lung. Tidal and minute volumes, inspiratory and expiratory flows, and dynamic compliance decreased and pulmonary flow resistance increased in the lung exposed to ozone. Because pulmonary edema preceded significant functional changes, the former is considered a more sensitive indicator of the extent of ozone toxicity. Edema occurred only in the lung breathing ozone.     

Enzyme changes during experimental silicotic fibrosis: I. PZ peptidase and collagen deposition in the lungs

In various time intervals from 2 to 22 weeks after intratracheal quartz dust instillation (25 mg DQ₁₂) the content of collagen proteins, deoxyribonucleic acid, soluble proteins, and collagen peptidase activity (PZ substrate) in rat lungs were estimated. In the period from 2 to 8 weeks the total amount of collagen as well as enzyme activity increased in parallel by about 200% in comparison to controls. In later periods (16 and 22 weeks after dust instillation) disproportions occurred. Collagen content in silicotic lungs continued to increase; the total activity of collagen peptidase in lungs started to decrease as did the specific enzyme activity. There was also observed a decrease in the content of lung proteins soluble in isotonic KCl. From 6 weeks onward, disc electrophoresis showed changes in the proportions of these proteins in dusted rats. The changes were particularly manifest in postalbumins, α₂- and γ-globulins, indicating more severe disorders in lung metabolism. There were found no differences in the amount and in the electrophoretic characteristics of serum proteins as well as in specific activity of PZ peptidase in serum of control and quartz-dusted rats. Neither control nor silicotic rat sera disclosed inhibitory effects on the activity of lung PZ peptidase. It appears that the increase of collagen proteins in lungs of animals dusted with quartz is also accelerated by the impairment of collagen breakdown.     

Development of silicotic lesions in the lungs of rats pre-exposed to coal fly ash.

The development of silicotic lesions was studied in the lungs of rats pre-exposed to a pulmonary load of coal fly ash. Exposure to quartz alone increased the wet weight, dry weight, and collagen content of the lungs. These changes were associated with an increase in the activity of lactate dehydrogenase, total proteins, and the cellularity of bronchoalveolar lavage. When the lungs of rats were pre-exposed to coal fly ash for 60 days and then exposed to quartz dust for periods similar to those used for exposure to quartz alone, the development of silicotic lesions and the laying down of collagen fibres was retarded, as judged by histopathological examination and biochemical analysis of the tissues for hydroxyproline contents. These changes in the lung tissue were associated with a significant reduction in the level of lactate dehydrogenase enzyme activity, total cell counts, and protein contents of the bronchoalveolar lavage derived from rats exposed to quartz.     

Development of silicotic lesions in the lungs of rats pre-exposed to coal fly ash

The development of silicotic lesions was studied in the lungs of rats pre-exposed to a pulmonary load of coal fly ash. Exposure to quartz alone increased the wet weight, dry weight, and collagen content of the lungs. These changes were associated with an increase in the activity of lactate dehydrogenase, total proteins, and the cellularity of bronchoalveolar lavage. When the lungs of rats were pre-exposed to coal fly ash for 60 days and then exposed to quartz dust for periods similar to those used for exposure to quartz alone, the development of silicotic lesions and the laying down of collagen fibres was retarded, as judged by histopathological examination and biochemical analysis of the tissues for hydroxyproline contents. These changes in the lung tissue were associated with a significant reduction in the level of lactate dehydrogenase enzyme activity, total cell counts, and protein contents of the bronchoalveolar lavage derived from rats exposed to quartz.     

Pulmonary fibrosis: Bronchoalveolar cell types and impaired function of alveolar macrophages in experimental silicosis

To determine the impact of chronic silicosis on lung cell populations and macrophage function, we quantified the types of cells in lavage fluid (bronchoalveolar cells) from guinea pigs with chronic silicosis and tested in vitro the function of alveolar macrophages. The fractions of neutrophils and giant cells in bronchoalveolar cells of silicotic animals were increased while the fraction of macrophages was slightly decreased compared to those of controls (intratracheal saline). The fractions of both lymphocytes and eosinophils were similar in the two groups. The majority of macrophages from silicotic lungs did not adhere to a glass surface. In addition, the random and stimulated migration of the macrophages from the silicotic lung was subnormal. However, adherent macrophages from silicotic animals spread on glass in both the absence and presence of a potent stimulant, N-formylmethionyl phenylalanine, as did cells from controls. These results suggest that the types of cells recovered by lavage from the silicotic lung mirror the inflammatory reaction in the pulmonary parenchyma and that the function of some alveolar macrophages in the silicotic lung is impaired.     

淡泉水对染尘大鼠脂质过氧化和超氧化物歧化酶活力的影响

目的：探讨淡泉水对染尘大鼠体内脂质过氧化物（LPO）和超氧化物歧化酶（SOD）的影响。方法：大鼠经气管注入石英粉尘后,饮淡泉水8周后,处死动物取肺、肝、脑组织测定LPO含量,取全血测SOD活力。取肺测定胶原蛋白和称肺重量。结果：染尘＋饮淡泉水组的肺、肝、脑组织LPO、肺胶原蛋白含量、肺重量明显低于染尘对照组（P＜0．05－P＜0．01）。血中SOD活力明显高于染尘对照组（P＜0．05）。结论：结果表明,该淡泉水能在一定程度上提高SOD活力。对SiO2引起的大鼠体内LPO的升高有一定的抑制作用。     

Abstacts from Current Literature

The role of ascorbic acid on developing pulmonary silicosis of normal and scorbutic guinea pigs was studied for 115 days. In normal silicotic guinea pigs an increasing concentration of ascorbic acid in lungs with the advancement of silicosis was observed. The increase of ascorbic acid was directly related to collagen percentage. Adrenal ascorbic acid showed an increase with lapse of time, and blood ascorbic acid did not show any alteration. In scorbutic silicotic guinea pigs the collagen fiber formation was retarded but the hydroxyproline contents and acid mucopolysaccharide remained the same as in normal silicotics.     

矽宁、汉防己甲素及磷酸羟基喹哌对实验性矽肺疗效的比较

对矽宁、汉防己甲素(汉甲)和磷酸羟基喹哌在等毒条件下进行了大鼠实验性矽肺的疗效研究,结果表明,治疗3个月后全肺湿、干重及肺胶原蛋白含量明显低于矽肺对照组,差别显著,但治疗组之间无明显差异;病理形态显示矽宁和汉甲组对矽肺纤维化有更明显的抑制作用,病灶间和肺泡腔内具有大量泡沫样细胞浸润。治疗组的肺巨噬细胞内均有细小的棕褐色颗粒。矽宁治疗组血清中SOD和铜蓝蛋白的含量明显低于其它治疗组。     

Lung lipids and pulmonary silicosis in rats

Summary In the development of pulmonary silicosis in rats studies on changes in the total, esterified, free cholesterol and phospholipids were made in lungs, liver and blood plasma over a period of 200 days. Total cholesterol, its fractions and phospholipid content increased with time in the lungs of silicotic animals. Histochemically sudanophilic materials were observed in the cytoplasm of pulmonary macrophages. Changes similar to those of lungs were not observed in liver and blood plasma, and it has been concluded that the increased lipid content of lungs during experimental pulmonary silicosis may be due to the localised degenerative action of silica on macrophages.     

利用原位杂交法研究实验性矽肺及石棉肺病变中Ⅰ型及Ⅲ型胶原的基因表达

利用~(35)S标记的3种前胶原[Proα_1 (Ⅰ) ,Proα_2(Ⅰ), Proα_1 (Ⅱ)]的cDNA探针与染石英尘的大鼠肺组织和染石棉尘的大鼠肺组织进行原位杂交。结果显示:(1)3种前胶原mRNA的杂交银颗粒在正常肺组织中稀疏地分布于狭窄的肺间隔中。在砂肺组织中主要分布于砂肺结节,增厚的间质及增生的胶原纤维旁。在石棉肺组织中主要分布在肉芽肿及增厚的间质中,与胶原纤维的分布一致。(2)前胶原mRNA表达细胞,即成纤维细胞,在加入石英或石棉尘后数目增多,每个细胞中前胶原mRNA的于表达水平高正常。提示胶原纤维的增生与成纤维细胞中胶原mRNA的增加有直接关系。     

矽肺大鼠和病人肺组织中Ⅰ型与Ⅲ型胶原纤维的分布及相对含量的研究

免疫酶标法用于观察肺组织中胶原的分布。显微分光光度法用于研究大鼠与矽肺病人的纤维化组织中Ⅰ型与Ⅲ型胶原的相对含量。染色中应用大鼠及人的抗Ⅰ型与Ⅲ型胶原多克隆抗体。Ⅰ型胶原分布于正常肺泡间隔及间质中。Ⅲ型胶原也在相同的部位存在。在由石英所致的大鼠纤维化肺组织中,Ⅰ型与Ⅲ型胶原在极度扩展的间质中聚集。Ⅲ型胶原是早期纤维化肺中主要增生的胶原。Ⅰ型胶原是纤维化后期主要增生的胶原。在矽肺病人肺组织中也见到同样的现象。染电焊烟尘的大鼠肺,直至180天以前,Ⅲ型胶原为主要积聚的胶原,而在180天以后,Ⅰ型胶原的增加才占优势。     

给与不给铝的矽肺大鼠肺中石英含量与病变的关系

利用红外光谱法测定了矽肺大鼠肺中矽结节组织和非结节组织的石英含量以及给予柠檬酸铝后的影响。结果表明,两组石英90%均集中在肺的矽结节,全肺石英总量的变化不明显,但山厂柠檬酸铝具有抑制石英的致纤维化能力,故每mg 石英所产生的胶原蛋白量有明显的差别。提示给予铝制剂防治后,肺组织可以承受更大量的石英打击。从而为进一步探讨肺中铝与石英的关系提供了依据。     

Laboratory testing of biological activity of ore mine dust: fibrogenicity, cytotoxicity, and hemolytic activity

The biological activity of respirable dust (particle size below 5 μm) from three ore mines was compared with its quartz content (14 to 36%) and with the occurrence of lung silicosis in miners. Three months after intratracheal instillation of 50 mg of dust suspensions, silicotic changes of the first and second degree (King's classification) developed in the lungs of rats. The content of hydroxyproline in the lungs increased by 60 to 110% in comparison to control values. No correlation was found between the quartz content of the dust and the histological changes or hydroxyproline levels. Cytotoxicity of the dust for guinea pig peritoneal macrophages and hemolytic activity in vitro for human erythrocytes did not correlate with its fibrogenicity. No new cases of lung silicosis have developed in the last 20 years in miners exposed in these ore mines to total dust concentrations below 10 mg/m³, although the incidence of silicosis was frequent in the past, when the dust concentrations were much higher.     

Comparing study of the effect of nanosized silicon dioxide and microsized silicon dioxide on fibrogenesis in rats

This study compares the effect of nanosized silicon dioxide (nanosized SiO2) and microsized silicon dioxide (microsized SiO2) particles on fibrogenesis in rats. Wistar rats were instilled intratracheally with saline, 20 mg of nanosized SiO2 or 20 mg of microsized SiO2, and were sacrificed at 1 and 2 months after instillation. The lungs of rats were analysed for the changes of lung/body coefficient and hydroxyproline content. Changes in pathology and fibrotic grade were observed by use of hematoxylin and eosin and Van Gieson dyeing. The expression of interleukin-4 (IL-4) and transforming growth factor-beta1 (TGF-beta1) was observed by use of immunohistochemical technique, and protein expression quantitatively analysed by image analysis. The lung/body coefficient and hydroxyproline content of nanosized SiO2 groups were significantly lower than those of microsized SiO2 groups at both 1 and 2 months after instillation (P<0.05 or P<0.01), but without significant differences from those of saline control groups. At 1 month after instillation, there were mainly cellular nodules (Stage I) in nanosized SiO2 group, while in microsized SiO2 group Stage II, II+ of silicotic nodules were observed. At 2 months after instillation, there were still Stage I of silicotic nodules in nanosized SiO2 group. In microsized SiO2 group mainly Stage II+, III of silicotic nodules were found. Quantity image analysis showed that the expressions of IL-4 and TGF-beta1 in nanosized SiO2 groups were significantly lower than those in microsized SiO2 groups (P<0.01), but without significant difference from those of saline control groups. Our experiment revealed that the effect of fibrogenesis of nanosized SiO2 might be milder than that of microsized SiO2 in rats, potentially resulting from nanoparticals tending to be diffused and easily translocated due to their ultrafine particle size compared to microsized particles.     

Silicosis,mixed dust pneumoconiosis,and lung cancer

A total of 764 autopsy cases with a pathological diagnosis of nonasbestos pneumoconiosis were investigated in a search for lung cancer: 146 patients bore 148 lung cancers (19.1%). The incidence of a lung cancer was associated positively with aging, longer occupational exposures, and smoking habits. A reverse correlation was found between carcinogenesis and the severity of pneumoconiosis. A statistically significant increase in the incidence of certain types of lung cancer (squamous cell carcinoma + small cell carcinoma) was found in silicotic lungs with massive fibrosis as compared to lungs with mixed dust pneumoconiosis of comparable severity. Although there appears to be no dose-response relationship in general between silicosis and lung cancer, it is advisable to consider the possibility that a presumptive silica-induced carcinogenesis might be masked by the severe fibrosis of a silicotic type, which obliterates the lung tissue in a different way from asbestosis, which is associated with epithelial proliferation. Am. J. Ind. Med. 32:595–599, 1997. © 1997 Wiley-Liss, Inc.     

Effects of sodium nitrate aerosol on cardiopulmonary function of dogs, sheep, and man

Submicronic aerosols of nitrate salts are synthesized in the atmosphere through further oxidation of nitrogen oxides produced during the burning of fossil fuels. This study was conducted to determine whether brief exposure to submicronic aerosol of sodium nitrate in high concentrations adversely affects the cardiopulmonary system. In all studies, submicronic aerosol of sodium chloride was used as a control. Anesthetized dogs breathing up to 10 mg/m³ of sodium nitrate (NaNO₃) aerosol for 7.5 min showed no significant alterations in respiratory resistance, static lung compliance, and functional residual capacity. A 4-hr exposure to NaNO₃ aerosol (5 mg/m³) produced neither significant changes in lung mechanics, functional residual capacity, pulmonary and systemic arterial pressures, cardiac output, heart rate, and arterial blood gases in anesthetized dogs nor a change in tracheal mucous velocity in conscious sheep. Both normal and asthmatic adults who breathed submicronic aerosol of NaNO₃ (up to 1 mg/m³) for 10 min showed no significant changes in lung volumes, distribution of ventilation, ear oximetry, dynamic mechanics of breathing, and oscillation mechanics of the chest-lung system. NaNO₃ aerosol (1000 μg/m³ for 10 min did not significantly change pulmonary capillary blood flow, diffusing capacity, oxygen consumption, and pulmonary tissue volume as measured by a rebreathing technique. Thus, brief exposure to high concentrations of submicronic aerosol of sodium nitrate does not produce immediate adverse effects on cardiopulmonary function of anesthetized dogs, conscious sheep, and normal and asthmatic adults.     

Whole-thorax irradiation induces hypoxic respiratory failure,pleural effusions and cardiac remodeling

To study the mechanisms of death following a single lethal dose of thoracic radiation, WAG/RijCmcr (Wistar) rats were treated with 15 Gy to the whole thorax and followed until they were morbid or sacrificed for invasive assays at 6 weeks. Lung function was assessed by breathing rate and arterial oxygen saturation. Lung structure was evaluated histologically. Cardiac structure and function were examined by echocardiography. The frequency and characteristics of pleural effusions were determined. Morbidity from 15 Gy radiation occurred in all rats 5 to 8 weeks after exposure, coincident with histological pneumonitis. Increases in breathing frequencies peaked at 6 weeks, when profound arterial hypoxia was also recorded. Echocardiography analysis at 6 weeks showed pulmonary hypertension and severe right ventricular enlargement with impaired left ventricular function and cardiac output. Histologic sections of the heart revealed only rare foci of lymphocytic infiltration. Total lung weight more than doubled. Pleural effusions were present in the majority of the irradiated rats and contained elevated protein, but low lactate dehydrogenase, when compared with serum from the same animal. Pleural effusions had a higher percentage of macrophages and large monocytes than neutrophils and contained mast cells that are rarely present in other pathological states. Lethal irradiation to rat lungs leads to hypoxia with infiltration of immune cells, edema and pleural effusion. These changes may contribute to pulmonary vascular and parenchymal injury that result in secondary changes in heart structure and function. We report that conditions resembling congestive heart failure contribute to death during radiation pneumonitis, which indicates new targets for therapy.     

Enzyme changes during experimental silicotic fibrosis. II. Intermediary metabolism enzymes of the lungs

The activity of seven important enzymes of intermediary metabolism in lung tissues was monitored during the development of experimental silicosis in rats. The enzymes were triosephosphate dehydrogenase (TPDH), lactate dehydrogenase (LDH), malate dehydrogenase (MDH), glycerol-3-phosphate NAD dehydrogenase (GPDH), hexokinase (HK), citrate synthase (CS), and hydroxyacyl-CoA dehydrogenase (HOADH). Changes were compared with the lung tissue response to nonfibrogenic corundum dust and with healthy lung tissues. In the developing silicotic lung tissue important disproportional activity changes take place in some enzymes (HK, TPDH, LDH, GPDH, HOADH); different, possibly less important changes occur after corundum application. The lung tissues of silicotic rats have an enhanced capacity for anaerobic degradation of saccharides with lactate as the end product. This finding can be related to the activation of collagen prolyl hydroxylase. The maximum changes in enzyme activities occur in the 2nd week of dust application.