Changes In Lungs Of Rats Research Articles

Pulmonary biochemical response to slate dust in rats.

The biochemical changes in rat lungs due to intratracheal instillation of 50 mg of slate dust have been studied up to 150 days of dust exposure. The remarkable feature of lung changes was the turnover of collagen in experimental animals after 90 days, reaching substantially higher values at 150 days. A concurrent increase in hexosamine and sialic acid contents was also observed. The phospholipid content in the whole lung tissue, as well as in the mitochondria, was generally higher in the dust-treated rats, particularly at the later stages. The mitochondrial cytochrome c oxidase and glutamate dehydrogenase activities increased, whereas monoamine oxidase was marginally affected. Mitochondria from experimental animals appeared to be in a swollen state, particularly at 120 days of exposure. The above results suggest that slate dust exerts its toxic effects by causing alterations in the tissue make-up as well as in the mitochondrial functioning of the lung.

Alterations in lung structure caused by inhalation of oxidants

Morphometric and morphologic methods have been used to evaluate changes in rat lungs caused by the inhalation of a variety of oxidants. Exposure to 100% oxygen causes diffuse pulmonary injury and leads to death after 66-72 h of exposure. The primary insult leading to death in rats exposed to hyperoxia is injury to pulmonary capillary endothelium. Sublethal exposure to hyperoxia was found to cause diffuse injury to all major components of the alveolar septum and was associated with destruction of approximately 50% of the pulmonary capillary endothelial cells. A corresponding decrease in pulmonary capillary surface area and capillary lumen volume also occurred. Exposure to ozone and to nitrogen dioxide in low concentrations did not cause a diffuse injury throughout the alveolar region of the lung, but rather led predominantly to structural alterations in terminal bronchioles and in their adjacent alveoli. Morphometric evaluation of animals exposed to 0.25 ppm ozone and to 2 ppm NO2 demonstrated quantitatively and qualitatively similar lesions. These lesions primarily involve injury and remodelling of the alveolar epithelium. These changes in the alveolar epithelium were also associated with the recruitment of increased numbers of alveolar macrophages to the proximal alveolar region. The different types of lung injury caused by various oxidants are most likely to be related to differences in their reactivity with tissue components and to differences in concentration, distribution, and diffusion characteristics of the oxidant gases.

Radiation Injury in Rat Lung: II. Angiotensin-Converting Enzyme Activity

To determine the role of endothelial dysfunction in the pathogenesis of radiation-induced pulmonary injury, lung angiotensin-converting enzyme (ACE) activity, arterial perfusion, and ultrastructure were examined from 1 to 150 days after a single exposure of 25 Gy of 60Co gamma rays to the right hemithorax of rats. Arterial perfusion to the irradiated right lung increased during the first 2 weeks, then decreased to approximately 80% of the left lung value at 30 days postirradiation. Perfusion of the irradiated lung continued to decline, and by 90-150 days was only 40% of that of the shielded lung. ACE activity in the irradiated right lung did not change significantly until 30 days after exposure, when it decreased to 72% of that in the left lung. ACE activity in the right lung declined steadily from 30 to 90 days postirradiation, then reached a plateau through 150 days at less than 20% of normal. Perivascular and interstitial edema was evident at 1 day after irradiation and persisted for 30 days. Endothelial cells exhibited blebbing, fragmentation, and increased basement membrane at 30 days. Mast cells were present in the septa, but interstitial collagen was not increased at that time. From 90 to 150 days postexposure, progressive obliteration of capillaries by fibrotic reactions was observed. Thus decreased ACE activity accompanies radiation-induced hypoperfusion and endothelial ultrastructural changes in rat lung. All of these reactions precede the development of pulmonary fibrosis.

Biochemical studies on the toxicity of slate mine dust.

As part of a detailed experimental study of the pathogenicity of disease of slate dust workers, the early biochemical changes in rat lung from 1 to 90 days after intratracheal inoculation of slate dust of particle size below 5 micron were investigated. A severalfold increase in free cell population (initially macrophages) was elicited by the dust. The free activity of acid phosphatase tended to increase along with a break of lysosomal latency with increasing exposure period. However, actual release of enzyme activity into the acellular fraction was low. The phospholipid content varied both in cellular and acellular fractions, indicating altered turnover of membrane lipids and surfactants. At advanced periods of the study, sialic was found to be released into the acellular fraction, indicating membrane damage. Considerable decrease in glucose-6-phosphate dehydrogenase activity and free sulfhydryl content and enhanced osmotic fragility of erythrocytes were also recorded. These results indicate the potential toxicity of slate mine dust.

Biochemical Studies on the Toxicity of Slate Mine Dust

As part of a detailed experimental study of the pathogenicity of disease of slate dust workers, the early biochemical changes in rat lung from 1 to 90 days after intratracheal inoculation of slate dust of particle size below 5 micron were investigated. A severalfold increase in free cell population (initially macrophages) was elicited by the dust. The free activity of acid phosphatase tended to increase along with a break of lysosomal latency with increasing exposure period. However, actual release of enzyme activity into the acellular fraction was low. The phospholipid content varied both in cellular and acellular fractions, indicating altered turnover of membrane lipids and surfactants. At advanced periods of the study, sialic was found to be released into the acellular fraction, indicating membrane damage. Considerable decrease in glucose-6-phosphate dehydrogenase activity and free sulfhydryl content and enhanced osmotic fragility of erythrocytes were also recorded. These results indicate the potential toxicity of slate mine dust.

Biochemical changes in rat lungs after exposure to nitrogen dioxide.

Sixty-day-old male, specific pathogen-free rats were exposed continuously to 5 or 15 ppm NO2 for 1-7 d. Lung tissue from exposed and control rats was then analyzed for biochemical and enzymatic parameters. The exposure resulted in increased lung enzymatic activities, including elevated protein and DNA contents and nonprotein sulfhydryl levels. Biochemical and enzymatic parameters generally increased maximally after 4 d and remained elevated for up to 7 d of continued exposure. The magnitude of these increases was higher for 15 than for 4 ppm NO2. The increases in biochemical and enzymatic parameters may have occurred in response to NO2-induced lung injury.

Structural and biochemical changes in rat lungs occurring during exposures to lethal and adaptive doses of oxygen.

The lungs of rats exposed to 100% O2 until death and to 85% O2 for as long as 14 days were studied using morphometric and biochemical techniques. The primary injury leading to death in rats exposed to 100% O2 was injury to the pulmonary capillary endothelium, where 44% of the endothelial cells were destroyed; there was a corresponding decrease in capillary surface area and in capillary lumen volume. Animals exposed to 85% O2 had proliferation and hypertrophy of alveolar Type II epithelial cells. In addition, 41% of the capillary endothelial cells were destroyed, but the endothelial cells that survived 7 days in 85% O2 were hypertrophied, and after this point no further destruction of the pulmonary capillary bed took place. Exposures to 85% O2 led to enhanced activity of the copper-zinc and manganese superoxide dismutases, which might be related to the apparently adaptive structural changes that occurred in the alveolar Type II epithelium and in the capillary endothelial cells.

Biochemical and physiologic changes in lungs of rats exposed to a cadmium chloride aerosol.

The purpose of this study was to examine the in vivo effects of acute exposure to a cadmium chloride aerosol on the activity of pulmonary enzymes and selected physiologic parameters that are altered by exposure to oxidant agents. Male rats were exposed for 1 hour to 0.5 per cent aerosol of cadmium chloride. At 1,5, and 11 days after exposure to cadmium chloride, exposed rats compared to control rats (data expressed as per cent of control values) had lung-to-body weight ratios of 192, 174, and 140 per cent; lung glucose-6-phosphate dehydrogenase activities of 90, 107, and 135 per cent; lung superoxide dismutase activities of 96, 101, and 132 per cent; tidal volumes of 62, 63, and 89 per cent; respiratory frequencies of 170, 145, and 108 per cent; and lung weight-specific static deflation volumes at 30 cm water of 30, 13, and 31 per cent. A zero-order clearance of cadmium from whole lung was observed, with a half-time of 27.4 days. Light microscopic examination of lung tissue revealed initial pulmonary edema on day 1 that progressed to interstitial pneumonitis on day 5, with some recovery by 11 days after exposure. The cadmium induced biochemical, physiologic, and pathologic alterations were similar to the responses observed in lungs of rats exposed to a wide variety of pulmonary irritants; thus, the changes observed may represent a nonspecific response to tissue injury.

Early changes in lungs of rats exposed to 70 per cent O2.

Sixty-six respiratory disease-free rats, divided into four groups, were exposed to 70% O2 for 1.5, 4, 7, and 10 days and compared with 31 littermates exposed to room air for equal times. Lung surfactant was separated from macrophages and potential serum protein contamination by differential centrifugation of endobronchial washings. In the O2-exposed rats, developing lung edema was demonstrated by decreased dried/fresh lung weight ratio and increased alveolar protein content at 7 and 10 days. At 7 days, lung compliance slope and hysteresis loop area decreased, while critical opening pressure increased. Ultrastructurally, the only abnormality seen was an irregular widening of the alveolar capillary basement membrane on day 10. Alveolar lecithin content decreased slightly during the 10 days exposure, but remained highly saturated, whereas whole lung lecithin content increased. These results suggest that the initial mechanical and morphological alterations in rats exposed to 70% O2 are related to lung edema and are not dependent upon lung surfactant alterations.

Estimation of equivalent pore radii of pulmonary capillary and alveolar membranes

Estimation of equivalent pore radii of pulmonary capillary and alveolar membranes

Ultrastructural changes in rat lungs induced by radioactive macroaggregated albumin.

Ultrastructural changes were found in lung tissue of rats sacrificed at various time intervals after intravenous injection of radioactive macroaggregated albumin. Contrary to the present concept of...