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P J Rombout

Publications and source records attributed to P J Rombout.

At least 19 recordsLinked to original sources
PubMed2001

Time study on development and repair of lung injury following ozone exposure in rats.

The aim of this study was to investigate the time course of lung injury in rats during acute and subchronic ozone exposure and during postexposure recovery. Rats were continuously exposed to 0.4 ppm ozone ( approximately 0.8 mg O(3)/m(3)) for 1, 3, 7, 28, or 56 days. Recovery from 3 days of exposure was studied at day 7, 14, and 28; recovery from 7 days of exposure was studied at day 14, 28, and 56, recovery from 28 days of exposure was studied at day 35 and 56, and recovery from 56 days of exposure was studied at day 136. The study included a correlated biochemical and morphological analysis of inflammatory responses, structural changes, and collagen content. The acute inflammatory response, as measured by an increase of polymorphonuclear cells and plasma protein in bronchoalveolar lavage (BAL) fluid, reached a maximum at day 1 and resolved largely within 6 days during ongoing exposure. Numbers of macrophages in BAL fluid increased progressively up to day 56, and slowly returned to near control levels when exposure was followed by postexposure recovery. Histological examination and morphometry of the lungs revealed centriacinar inflammatory responses throughout ozone exposure. Centriacinar thickening of septa was observed at day 7. Ductular septa, thickened progressively at days 7, 28, and 56 of exposure, showed increased collagen upon exposure at day 28, which was further enhanced at exposure at day 56. Increased collagen content in lungs, as measured biochemically by hydroxyproline concentration, was observed at exposure day 56. Collagen content was not different from control at day 56 when 7 or 28 days of exposure was followed by postexposure recovery. After continuous ozone exposure, respiratory bronchioles were present in an increasing degree, and remained present after a recovery period. The results of this study clearly show that after continuous exposure to O(3) some acute effects, such as protein and albumin content, and neutrophil influx in BAL fluid, returned to control levels within a few days. However, other parameters, such as the alveolar macrophage response and structural changes such as the presence of terminal bronchioles, thickening of ductular septa by enhanced cellularity, and collagen formation, persisted or progressively increased during continued exposure. Postexposure recovery seems to partly resolve these subchronic responses (macrophages response, septal cellularity), whereas other effects (collagen increase and respiratory bronchioles formation) do not disappear.

Albumins↗
PubMed1999

Interspecies differences in time course of pulmonary toxicity following repeated exposure to ozone.

To compare the extent and time course of pulmonary injury and repair in 3 rodent species, rats, mice and guinea pigs were continuously exposed for 3, 7, 28, and 56 days to 400 and 800 microg O3/m(3) (0.2 and 0.4 ppm). Recovery from 28 days of exposure was studied at 3, 7, and 28 days after exposure. Pulmonary injury and repair was studied at various time points by histology, electron microscopy, morphometry, and biochemistry. In all 3 species a concentration-related centriacinar inflammation occurred, with a maximum after 3 days of exposure. The number of alveolar macrophages and the pulmonary cell density in the centriacinar region increased progressively until 56 days of exposure, with the guinea pig the most sensitive species. Only the mouse displayed a concentration and exposure-time dependent hypertrophy of bronchiolar epithelium. After 56 days of exposure to 800 microg O3/m(3) in the rat and the guinea pig, giant lamellar bodies in type II cells were present. Exposures for 3 and 7 days at near ambient ozone concentrations (400 microg O3/m(3)) resulted in significantly elevated lung enzyme activities in the mouse, and in significant histological and morphometric changes in all 3 species. In rat and guinea pigs exposures for 56 days resulted in alveolar duct fibrosis. The highest biochemical response and the slowest recovery from ozone exposure were seen in the mouse. Histology, morphometry, and biochemistry revealed a total recovery from a 28-day exposure period in rats after 28 days, while in guinea pigs the ductular septa were still thickened and in mice all enzyme activities were still elevated in comparison with control values. In conclusion, the response of mice to ozone was evaluated as most severe, followed by those of guinea pigs and least in rats.

Administration, Inhalation↗
PubMed1995

Dose-effect models for ozone exposure: tool for quantitative risk estimation.

Short-term ozone exposure causes lung function decrements, increased airway reactivity, airway inflammation, increased respiratory symptoms and hospital admissions. Exposure to long-term elevated ozone levels seems to be associated with reduced lung function (aging), increase of respiratory symptoms, exacerbation of asthma, and airway cell and tissue changes. Health risk caused by exposure to ozone has been evaluated mainly in a qualitative way by comparing ozone air quality data with health-based guidelines or standards. A preliminary approach to quantifying health risk from short-term exposure to oxidant air pollution has been taken by expert judgement, describing known or expected effects at specific levels of ozone. For quantitative assessment of the health impact of distinct ozone exposure conditions (acute, repeated daily, chronic) specific exposure-dose-response models are being developed which can be linked to human exposure data. Exposure-(dose-)response models using data from epidemiological, human-clinical and animal toxicity studies are presented.

Air Pollution↗
PubMed1995

Effect of ozone exposure on maximal airway narrowing in non-asthmatic and asthmatic subjects.

1. Ozone is a major constituent of air pollution in the summer. Epidemiological studies have demonstrated that there is an increase in hospital admissions for respiratory diseases 1 day after peak levels of ambient ozone. This may be due to an increase in the responsiveness of the airways to bronchoconstrictor stimuli. 2. In the present study we therefore studied the effect of a controlled exposure to ozone on the maximal degree of airway narrowing to a non-specific bronchoconstrictor, methacholine, 12 h after exposure. Both non-asthmatic and mild-asthmatic volunteers were exposed to ozone. 3. The study had a single blind design. Experimental exposures were to filtered air, 0.40 ppm ozone and filtered air respectively, at 1-week intervals. The duration of each exposure was 2 h with alternating periods of 15 min rest and exercise. At 12 h after exposure, methacholine inhalation challenge tests and sputum induction were performed. 4. Twelve hours after exposure to ozone there was a significant increase in the maximal degree of airway narrowing to methacholine (P < 0.02) compared with exposure to air, in non-asthmatic as well as asthmatic subjects. These physiological changes were accompanied by a significant rise in the percentage of neutrophils in induced sputum (P < 0.02). All changes had returned to baseline values 1 week after exposure to ozone. 5. Exposure to ozone causes a transient increase in the maximal degree of airway narrowing to methacholine in both non-asthmatic and asthmatic subjects. These laboratory results, obtained using relatively high ozone exposure in carefully selected subjects, might provide an explanation for the temporal relationship between ambient ozone levels and hospital admissions for asthma.

Adult↗
PubMed1994

Attenuation of acute lung injury by ozone inhalation--the effect of low level pre-exposure.

The attenuating influence of a pre-exposure of rats to a low concentration of ozone (O3) for 7 days on a subsequent O3 challenge was investigated. Effects of O3 were quantified by measuring indicators of lung permeability and inflammation in bronchoalveolar lavage fluid. The results suggest that pre-exposure to relatively low levels of O3 produces a diminished permeability response in lower airways of rats upon a following challenge with a higher level of O3. Extrapolated to human exposure situations, these data suggest that health effect evaluation of repeated exposure periods of enhanced O3 levels is rather complex and needs further investigation.

Administration, Inhalation↗
PubMed1993

Desferrioxamine treatment reduces histological evidence of lung damage in rats after acute nitrogen dioxide (NO2) intoxication.

1. In previous studies a rat inhalation model was developed to investigate the efficacy of treatment in acute NO2 intoxication. 2. Desferrioxamine was administered intravenously to study its effect on histological alterations in lung tissue in rats after acute NO2 exposure. 3. Twenty four hours after exposure to 175 ppm NO2 for 10 minutes the lung injury observed by light microscopy in the desferrioxamine treated rats was less pronounced than in the saline treated rats. 4. Desferrioxamine appeared to provide more protection with a dose of 100 mg kg-1 24 h-1 than with 200 mg kg-1 24 h-1.

Administration, Inhalation↗
PubMed1992

Differences in pulmonary biochemical and inflammatory responses of rats and guinea pigs resulting from daytime or nighttime, single and repeated exposure to ozone.

Rats and guinea pigs were exposed to 0.8 mg ozone (O3)/m3 (approximately 0.4 ppm) for 12 hr during the daytime, 12 hr during the nighttime, or continuously to investigate circadian variation in O3-induced pulmonary toxicity during single and repeated O3 exposures. Biomarkers in bronchoalveolar lavage (BAL) fluid and lung tissues were measured as indicators of biochemical and inflammatory responses. Nighttime O3 exposure of rats resulted in larger increases of protein, albumin, and inflammatory cells in BAL fluid compared to those after daytime O3 exposure and this daytime-nighttime difference was statistically significant (p < 0.05). Single daytime or nighttime O3 exposure of guinea pigs resulted in comparable increases of BAL fluid proteins and inflammatory cells without a daytime-nighttime difference. Nighttime and continuous O3 exposure of rats for 3 days resulted in comparable increases in lung antioxidant enzyme activities, both of which differed statistically from effects from daytime O3 exposures (p < 0.05). Continuous O3 exposure of guinea pigs for 3 days caused, in general, statistically larger increases in lung tissue parameters compared to nighttime O3 exposures (p < 0.05). These results suggest that the extent of O3-induced acute pulmonary biochemical and inflammatory responses is directly related to the level of physical and respiratory activity. For rats, effects from continuous O3 exposure appear to be controlled by the nighttime, physically active period. In guinea pigs, the comparable responses following daytime or nighttime O3 exposure seem in accordance with their random behavioral daily activity pattern. This study supports the view that physical activity-related increases in inhaled dose significantly enhance the pulmonary O3 responses.

Administration, Inhalation↗
PubMed1992

Rat model to investigate the treatment of acute nitrogen dioxide intoxication.

1. The pulmonary toxic events induced by acute nitrogen dioxide (NO)2 exposure were studied in the rat to develop an inhalation model to investigate therapeutic measures. 2. A good correlation was observed between the lung weights and severity of the atypical pneumonitis. The pulmonary effects observed, became more pronounced with increasing NO2 concentrations (0, 25, 75, 125, 175 or 200 ppm, 1 ppm NO2 = 1.88 mg m-3 NO2) and exposure times (5, 10, 20 or 30 min). 3. An adequate NO2 concentration is 175 ppm, because it can induce a severe lung injury without mortality. This makes it possible to investigate suitable therapeutic interventions for several days. 4. Following acute inhalatory NO2 intoxication, transformation of NO2 to nitrate is presumably more notable than transformation to nitrite. 5. The transformation of NO2 to nitrate in lung tissue causes a slight increase in the serum nitrite concentration, which does not induce measurable formation of methaemoglobin. 6. Presumably, methaemoglobin does not contribute to the toxicity of NO2 intoxication.

Administration, Inhalation↗
PubMed1991

Structural and biochemical effects in lungs of Japanese quail following a 1-week exposure to ozone.

The effect of ozone inhalation on birds was investigated. Japanese quail were exposed continuously to 0, 0.3, 1.0, and 3.0 mg/m3 ozone (0, 0.15, 0.50, and 1.50 ppm, respectively) for 7 days. Pulmonary effects were determined by light and electron microscopy as well as by biochemistry. Focal areas of hemorrhages were noticed in the birds exposed to 1.0 mg/m3 ozone. Additional effects after exposure to 1 mg/m3 included loss of cilia in trachea and bronchi, an inflammatory response, and necrosis of air capillary epithelial cells. Following exposure to 3 mg/m3 many atria of tertiary bronchi were completely obstructed by extensive hemorrhages, metaplasia of atrial wall cells, and hypertrophy of smooth muscle cells. Lung biochemistry data revealed that in the 3 mg/m3 group lactate dehydrogenase, glucose-6-phosphate dehydrogenase, and glutathione reductase activities were significantly increased. In the 0.3 and 1.0 mg/m3 exposure groups no effects on lung antioxidant enzymes were observed. In conclusion, Japanese quail appear to respond to ozone exposure in a different way than mammals. Since no signs of repair in air capillary epithelium after 7 days of continuous exposure were observed, the quail seems to lack the morphological and biochemical repair ability as is observed in mammals. Therefore, more research of the effects of ozone on birds seems to be necessary, both from a mechanistic and an ecological point of view.

Administration, Inhalation↗
PubMed1990

Effects of ozone, hexachlorobenzene, and bis(tri-n-butyltin)oxide on natural killer activity in the rat lung.

The respiratory tract is a major route of exposure to noxious agents as well as pathogens such as viruses. Natural killer (NK) activity is an important first line of defense to virally infected cells as well as certain neoplasms; therefore, testing the effects of exposure to toxic compounds on this activity is important in understanding the immunotoxic potential of the compound. Lymphoid cell suspensions, obtained after enzymatic dispersion of rat lungs and purification over nylon wool columns, showed in vitro natural killer activity toward YAC lymphoma cells. Validation of the test with well-known NK activity stimulators such as Bacillus Calmette-Guérin (BCG), interleukin-2 (IL-2), interferon (IFN), and inhibitors like anti-asialo-GM1 (ganglio-n-tetrasylceramide) antibody confirmed the reliability of the test as an assay for detecting NK activity in rat lungs. Using this assay, we studied the effects of exposure to ozone (O3), hexachlorobenzene (HCB), and bis(tri-n-butyltin)oxide (TBTO) on NK activity in rat lung. Inhalation exposure to O3 for 7 days at 0.4 and 0.8 mg/m3 resulted in stimulation, and exposure at 1.6 mg O3/m3 resulted in suppression of NK activity. Oral exposure to HCB in concentrations of 150 and 450 mg/kg food for 6 weeks suppressed NK activity in rat lungs in a dose-related manner. This was also true for 6 weeks of oral exposure of rats to 20 and 80 mg TBTO/kg food, but to a lesser extent. In summary, we have developed and validated a method to measure the effects of (toxic) substances on NK activity in rat lung.

Animals↗
PubMed1990

Interactive effects of ozone and formaldehyde on the nasal respiratory lining epithelium in rats.

The combined effects on the nasal epithelium of mixtures of ozone and formaldehyde at cytotoxic and noncytotoxic concentrations were examined. Male Wistar rats were exposed by inhalation during 22 h/d for 3 consecutive days to 0.3, 1.0, or 3.0 ppm formaldehyde, or to 0.2, 0.4, or 0.8 ppm ozone, or to mixtures of 0.4 ppm ozone and 0.3, 1.0, or 3.0 ppm formaldehyde, or to 1.0 ppm formaldehyde and 0.2, 0.4, or 0.8 ppm ozone, or they were sham-exposed to clean air. The noses were examined for pathological changes at six standard cross levels by light microscopy and for epithelial cell proliferation by counting [3H-methyl]thymidine-labeled cells at cross levels II and III. Ozone at 0.4 ppm or 0.8 ppm or formaldehyde at 3 ppm enhanced cell proliferation at cross level II at all locations, except for the epithelium of the septum, which was not affected by ozone. At cross level III ozone alone did not induce cell proliferation, but formaldehyde at 0.3 and 1 ppm tended to reduce cell proliferation while at 3 ppm proliferation was slightly stimulated. The combined exposure to 0.4 ppm ozone and 0.3 ppm formaldehyde induced less cell proliferation at cross levels II and III when compared with that of 0.4 ppm ozone alone. Less cell proliferation was also seen at cross level II when animals were exposed to 0.4 or 0.8 ppm ozone in combination with 1 ppm formaldehyde than when exposed to these ozone concentrations alone. A more than additive increase in cell proliferation was found at cross level II after exposure to 0.4 ppm ozone in combination with 3 ppm formaldehyde, and at cross level III in animals exposed to 0.4 ppm ozone and 1 or 3 ppm formaldehyde. Treatment-related histopathological nasal changes, such as disarrangement, loss of cilia, and hyper/metaplasia of the epithelium were seen at 0.2, 0.4, and 0.8 ppm ozone and at 3 ppm formaldehyde. Simultaneous exposure to both materials did not noticeably affect type, degree, and size of the microscopic nasal lesions.

Animals↗
PubMed1990

Surface morphology and morphometry of rat alveolar macrophages after ozone exposure.

As the ultrastructural data on the effects of ozone on pulmonary alveolar macrophages (PAM) are lacking, transmission (TEM) and scanning (SEM) electron microscopy were performed on rat PAM present in alveolar lavages following exposure to ozone. Rats were continuously exposed for 7 d to ozone concentrations ranging from 0.25 to 1.50 mg/m3 for 7 d followed by a 5-d recovery period. Additionally, morphometry on lung sections was performed to quantitate PAM. In a second experiment rats were continuously exposed to 1.50 mg O3/m3 for 1, 3, 5, or 7 d. To study the influence of concurrent ozone exposure and lung infection, due to Listeria monocytogenes, rats were exposed for 7 d to 1.50 mg O3/m3 after a Listeria infection. The surface area of lavaged control PAM was uniformly covered with ruffles as shown by SEM and TEM. Exposure to 0.5 mg ozone/m3 for 7 d resulted in cells partly covered with microvilli and blebs in addition to normal ruffles. The number of large size PAM increased with an increase in ozone concentration. After 1 d of exposure, normal-appearing as well as many small macrophages with ruffles and scattered lymphocytes were seen. Lavage samples taken after 5 or 7 d of exposure showed an identical cell composition to that taken after 3 d of exposure. After Listeria infection alone, lavage samples consisted of mainly lymphocytes and some macrophages. Small quantitative changes, such as an increase in the number of polymorphonuclear neutrophils and large-size PAM, occurred in lavages after ozone exposure and infection with L. monocytogenes. Morphometric examination of lung sections revealed a concentration-related increase in the number of PAM, even in animals exposed to 0.25 mg ozone/m3 for 7 d. Centriacinar regions were more severely affected than other regions of lung tissue. By 5 d after termination of exposure to ozone, the number of lysozyme-positive alveolar cells was still significantly increased in centriacinar areas of the lung. The results indicate that ozone exposure causes major changes in the number, size, and surface morphology of PAM in rat lung. Furthermore, the results presented here suggest that changes in alveolar macrophage function are reflected by morphological changes.

Animals↗
PubMed1989

Study of the effects of ozone in emphysematous rats.

The effects of short-term exposure to ozone on control and elastase-induced emphysematous rats were examined to investigate whether emphysema would change the pulmonary susceptibility to oxidant air pollution. Emphysema was induced in rats after a single intratracheal instillation of 0.2 IU elastase/g body weight. Histologically, panacinar emphysema was apparent at 2, 4, 8, and 16 wk, that is, the total duration of the experiment. The diagnosis was confirmed by morphometry: the mean linear intercepts (MLI) of elastase-treated rats were significantly increased at all observation times, whereas the internal surface areas (ISA) of the elastase-treated rats were significantly decreased. In addition, pulmonary function tests provided supportive evidence for the diagnosis of emphysema. Respiratory system compliance and functional residual capacity showed a significant increase in elastase-treated rats. No differences in inspiratory capacity or in forced vital capacity between control rats and elastase-treated rats were observed. The above data are indicative for a rat model for elastase-induced emphysema. Short-term exposure to ozone of elastase-treated rats revealed panacinar emphysema, including an inflammatory response in the centroacinar region. No differences in MLI as well as in ISA between ozone-exposed rats (with or without emphysema) and their respective controls were observed. Short-term exposure to ozone induced an identical, significant increase in protein content, lactate dehydrogenase, glucose-6-phosphate dehydrogenase, and glutathione peroxidase activities in lungs of normal and emphysematous rats. Moreover, these results strongly suggest that emphysematous rats are not more susceptible to ozone than nonemphysematous rats.

Air Pollutants↗
PubMed1988

Phosphatidylcholine synthesis in isolated type II pneumocytes from ozone-exposed rats.

Phosphatidylcholine (PC) synthesis by alveolar type II cells, as an indicator for the production of pulmonary surfactant, was studied after a 4-h exposure of rats to 4 mg ozone/m3 (2 ppm). Lung ravage fluid analysis after exposure revealed significant increases in proteins, which is indicative for pulmonary injury. When type II cells were isolated immediately and thereafter cultured for 20 h, the rate of PC synthesis in cells derived from ozone-exposed rats was not significantly different from that in cells from unexposed controls. Yet, a decreased rate of PC synthesis was observed when these cells were subsequently exposed to ozone in vitro. The activity of the enzyme glycerolphosphate acyltransferase (GPAT) was slightly enhanced in cultured type II cells isolated from ozone-exposed rats, while the lysophosphatidylcholine acyltransferase (LPCAT) activity was unchanged. However, ozone exposure of rats did result in a significant decrease of PC synthesis when measured in freshly prepared type II cell suspensions, although both GPAT and LPCAT activities were not affected. It is concluded that a decrease in pulmonary surfactant related PC synthesis after ozone exposure of rats can be demonstrated in freshly isolated type II pneumocytes. Cultured type II cells from exposed rats lack this effect and are therefore less useful to study changes in phospholipid biosynthesis after in vivo ozone exposure. The data on in vitro ozone exposure of cultured type II cells, however, support the view that ozone may impair pulmonary surfactant production.

1-Acylglycerophosphocholine O-Acyltransferase↗
PubMed1988

Effects of ozone on the defense to a respiratory Listeria monocytogenes infection in the rat. Suppression of macrophage function and cellular immunity and aggravation of histopathology in lung and liver during infection.

We have investigated the effect of exposure to ozone on defense mechanisms to a respiratory infection with Listeria monocytogenes in the rat. For this purpose rats were continuously exposed to O3 concentrations ranging from 0.25 to 2.0 mg/m3 for a period of 1 week. In this model defense to a respiratory infection with Listeria depends on acquired specific cellular immune responses, as well as on natural nonspecific defense mechanisms. The results confirm earlier findings that show that ozone exposure can suppress the capacity of macrophages to ingest and kill Listeria. Moreover, the results show that ozone can also have a suppressive effect on the development of cellular immune responses to a respiratory Listeria infection, i.e., on T/B ratios in lung draining lymph nodes, delayed-type hypersensitivity responses to Listeria antigen, and lymphoproliferative responses in spleen and lung draining lymph nodes to Listeria antigen. The effects on the specific immune responses are especially overt if exposure to the oxidant gas occurs during an ongoing primary infection. The pathological lesions induced by a pulmonary Listeria monocytogenes infection were characterized by multifocal infiltrates of histiocytic and lymphoid cells. The foci sometimes had a granulomatous appearance. Moreover, the cellularity of the interstitial tissues was increased. In the lung many diffuse alveolar macrophages could be seen in the alveoli. Ozone exposure greatly increased the severity of the lung lesions and also of liver lesions resulting from the pulmonary infection. A prominent finding was the formation of granulomas in ozone-exposed and Listeria-infected rats. This increased severity of the lesions after ozone exposure and subsequent infection with Listeria was presumably not a result of additive ozone and Listeria-induced lesions, but rather an effect of ozone-induced impaired clearance of the bacteria, caused by depressed macrophage activity and cellular immunity. T-cell-dependent immune responses form an important component of defense to respiratory infections with bacteria and viruses, and possibly also to neoplasms. Since our study unequivocally shows an effect on T-cell-dependent immunity, ozone exposure has to be judged potentially hazardous with respect to such challenges of the lung.

Animals↗
PubMed1988

Qualitative and quantitative changes in cytochrome P-450-dependent xenobiotic metabolism in pulmonary microsomes and isolated Clara cell populations derived from ozone-exposed rats.

The effect of a prolonged ozone exposure (1.6 mg ozone/m3; 7 d; 24 h/d) on pulmonary cytochrome P-450-dependent xenobiotic metabolism was studied both in whole rat lung as well as in isolated bronchiolar Clara cell preparations. Ozone exposure was demonstrated to result in significant quantitative but also qualitative changes. All components of the pulmonary microsomal electron transport system appeared to be significantly increased in the lungs of exposed animals both per lung and per gram lung, although increases were no longer observed when expressed per milligram microsomal lung protein. Remarkably, it was demonstrated that the increases in the components of the pulmonary cytochrome P-450 system were not accompanied by a concomitant increase in all cytochrome P-450-dependent substrate conversions. In whole-lung microsomes ethoxycoumarin O-deethylase and ethoxyresorufin O-deethylase activities were unchanged or even significantly reduced when expressed per lung, per gram lung, per milligram microsomal protein, or per picomole cytochrome P-450. In contrast to these observations, pentoxyresorufin O-dealkylation appeared to be significantly increased upon ozone exposure when expressed per lung, per gram lung, and even per picomole cytochrome P-450. Clara cell populations isolated from ozone exposed rats showed a comparable qualitative shift in cytochrome P-450-dependent substrate conversion characteristics. On a cellular basis, ozone exposure resulted in a significant reduction of ethoxycoumarin and ethoxyresorufin O-deethylation and did not affect pentoxyresorufin O-dealkylase activity. Additional experiments, in which ozone-mediated inactivation of microsomal cytochrome P-450-dependent substrate metabolism was studied in vitro, demonstrated that the qualitative changes observed after in vivo exposure cannot be ascribed to a disproportional inactivation of different cytochrome P-450 isoenzymes. Based on these results and on lung morphometrics and cell isolation data presented, the observed effects should rather be ascribed to (1) the proliferation of cytochrome P-450 containing cell populations and (2) intrinsic cellular biochemical changes. The quantitative and qualitative ozone-induced changes in pulmonary cytochrome P-450-linked enzyme characteristics in whole lung and within specific lung cells, as demonstrated in the present study, may be expected to have important implications for the toxicity of xenobiotics whose (de)toxification depends on pulmonary cytochrome P-450-dependent metabolism.

Animals↗
PubMed1986

Influence of exposure regimen on nitrogen dioxide-induced morphological changes in the rat lung.

Experiments were performed to study the influence of concentration, exposure pattern, and length of exposure on the degree and extent of morphological alterations in the NO2-exposed rat lung. Four weeks of continuous exposure to 20 mg NO2/m3 consecutively revealed damage and loss of cilia, replacement of desquamated type I pneumocytes by type II pneumocytes resulting in a cuboidal epithelial lining, an influx of alveolar macrophages, and hypertrophy and hyperplasia of the bronchiolar epithelium. The animals recovered almost completely from the induced lesions within 8 days. Continuous exposure to 1, 2.5, or 5 mg/m3 displayed minimal alterations in the 5 mg/m3 group. The effects increased with exposure time. Intermittent or continuous exposure to 20 mg NO2/m3 resulted in minor differences after 4 weeks. The onset of the lesions was delayed and the massive influx of alveolar macrophages in the continuously exposed animals failed to appear in the intermittently exposed animals. This work demonstrates that in subacute experiments: Concentration plays a more important role in inducing pulmonary lesions than exposure time when the product of concentration and time is kept constant. This effect is stronger during intermittent exposure than during continuous exposure. Continuous exposure seems to be a more important factor with regard to a macrophage response than intermittent exposure. The rat lung has a large capacity to repair almost completely from damage caused by short-term NO2 exposure.

Animals↗