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Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multiple reactive oxygen species-induced epithelial injury by glucose, glucose oxidase, and lactoperoxidase instillation in the lung results in a progressive interstitial fibrosis. To test the hypothesis that multiple pulmonary inflammatory responses alone would not result in fibrosis, three sequential inflammatory reactions were produced at weekly intervals in hamster lungs via intratracheal instillation of human recombinant C5a. Numbers of neutrophils and total inflammatory cells in bronchoalveolar lavage (BALF) increased significantly at 24 h after each C5a treatment compared with saline controls. Neutrophils increased by 3-, 33-, and 34-fold compared with the corresponding controls at 24 h after the first, second, and third doses, respectively, but returned to control levels by six days postinstillation. LTB4 levels increased by 24% and 20% compared with the corresponding controls at 24 h after the first and second doses but were not different from controls at other times. Hydroxyproline levels in treated animals did not differ significantly from control levels throughout the study. Protein levels were significantly increased at 24 h after the second and third doses and six days after the third dose compared with the corresponding controls. Occasional foci of neutrophils in alveolar spaces were observed at 24 h after each dose, but they decreased in frequency after six days. No foci of neutrophils were observed six days after the final dose, although some epithelial degeneration was observed by transmission electron microscopy. Our results indicate that pulmonary inflammation resulting from repeated influx of neutrophils in response to multiple instillations of C5a in the lung does not cause sufficient injury to result in pulmonary fibrosis.
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PMID:Repeated episodes of C5a-induced neutrophil influx do not result in pulmonary fibrosis. 165 81

The present study determined whether inhibitors of angiotensin converting enzyme (ACE) can ameliorate radiation-induced pulmonary endothelial dysfunction and pulmonary fibrosis in rats sacrificed 2 months after a range of single doses of 60Co gamma rays to the right hemithorax. Four indices of pulmonary endothelial function were monitored: right lung ACE and plasminogen activator (PLA) activity, and prostacyclin (PGI2) and thromboxane (TXA2) production. Hydroxyproline (HP) content served as an index of pulmonary fibrosis. Rats consumed either control powdered chow or feed containing one of five modifying agents continuously after irradiation. The modifiers included three ACE inhibitors: Captopril, CL242817, and CGS13945, respectively, a thiol, a thioacetate, and a nonthiol compound. All of the ACE inhibitors are analogues of proline. Two additional modifiers were tested: penicillamine, a thiol with no ACE inhibitory activity; and pentoxifylline, a vasodilator that is neither a thiol nor an ACE inhibitor. Radiation produced a dose-dependent decrease in lung ACE and PLA activity, and an increase in PGI2 and TXA2 production and in HP content. All ACE inhibitors attenuated the radiation-induced suppression in lung ACE and PLA activity. All thiol or thioacetate compounds ameliorated the radiation-induced increase in PGI2, TXA2, and HP. The two agents that were both thiols and ACE inhibitors (Captopril and CL242817) spared all of the radiation reactions, while the compound that was neither a thiol nor an ACE inhibitor (pentoxifylline) spared none of the reactions. These data suggest a novel application for ACE inhibitors in general, and for Captopril in particular, as modifiers of radiation pneumotoxicity.
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PMID:Radiation pneumotoxicity in rats: modification by inhibitors of angiotensin converting enzyme. 173 1

Because in vitro studies have shown inhibition of fibroblast proliferation and collagen synthesis by interferon, we tested the hypothesis that murine gamma interferon inhibits bleomycin-induced pulmonary fibrosis in mice. Mice were divided into the following groups: saline plus vehicle (27), saline plus interferon (29), bleomycin plus vehicle (26), and bleomycin plus interferon (26). Bleomycin or saline were given intratracheally once at the beginning of the experiment and vehicle (phosphate-buffered saline) or interferon was given intramuscularly daily. Mice were killed at 14 or 21 days of the experiment. About half of the mice from each group were used for collagen biochemistry and half for bronchoalveolar lung lavage, transmission electron microscopy (TEM), and morphometry. Hydroxyproline content showed a significant reduction in bleomycin plus interferon compared to bleomycin plus vehicle mice at 21 days. The saline plus vehicle and saline plus interferon mice showed no difference in hydroxyproline content. Similarly, bronchoalveolar lavage showed no differences between saline plus vehicle and saline plus interferon mice; however, all mice treated with bleomycin showed significant increases in total cells as compared to saline treated mice. At 14 and 21 days in bronchoalveolar lavage there were significantly more lymphocytes in bleomycin plus interferon compared to bleomycin plus vehicle mice. In bronchoalveolar lavage, there were usually fewer neutrophils, monocytes and macrophages in bleomycin plus interferon compared to bleomycin plus vehicle mice. Morphometric estimates of the volume of lesion within lung showed no significant differences among the bleomycin treated groups. Stainable collagen fibers were less, but not significantly, in the bleomycin plus interferon compared to bleomycin plus vehicle mice. The number of fibroblasts per volume of lesion was significantly decreased at 14 and 21 days in bleomycin plus interferon compared to bleomycin plus vehicle mice. The total volume of lymphocytes in interstitial lesions was significantly greater at 14 and 21 days in bleomycin plus interferon mice compared to bleomycin plus vehicle mice. These results suggest an inhibitory action of gamma interferon on collagen accumulation and fibroblast proliferation associated with lymphocyte accumulation in the lungs of mice following bleomycin administration.
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PMID:Effect of murine gamma interferon on the cellular responses to bleomycin in mice. 246 44

We tested the efficacy of 2 antifibrotic agents, the proline analogue cis-4-hydroxy-L-proline (cHyp) and the lathyrogen beta-aminopropionitrile (BAPN), on experimental silicosis in hamsters. Silica (75 mg) was instilled intratracheally, and 3 months later lung hydroxyproline content, the volume density of silicotic nodules in lung parenchyma, fluid-filled lung pressure-volume curves, body weight and survival were measured. Animals were injected with cHyp, 200 mg/kg body weight, or BAPN, 150 mg/kg body weight, twice daily for 3 months. Hydroxyproline contents (mg/lung) at 3 months were: control, 0.8 +/- 0.1; silica, 1.4 +/- 0.1 (P less than 0.05 compared to control); silica-cHyp, 1.2 +/- 0.2; silica-BAPN, 1.4 +/- 0.1 (both NS compared to silica). The volume density of granuloma (% of surface area) was: silica, 0.7 +/- 0.1; silica-cHyp, 5.9 +/- 1.0; silica-BAPN, 9.7 +/- 1.5 (both P less than 0.5 compared to silica). There was no difference among the groups as assessed by lung pressure-volume curves. No toxic effects were produced on the skeletal system as assessed by bone hydroxyproline content and skeletal roentgenograms. Final body weights (g) were: silica, 114 +/- 5; silica-BAPN, 108 +/- 6; silica-cHyp, 88 +/- 7 (the latter P less than 0.05 compared to silica). Survival (%) was: silica, 62%; silica-BAPN, 34%, silica-cHyp, 28% (both P less than 0.05 compared to silica). These data show that cHyp and BAPN treatment did not prevent silica-induced pulmonary fibrosis, led to more extensive silicotic nodules, and were toxic. Both cHyp and BAPN have some efficacy in other models of fibrosis, and the observations in the present study could be specific to silicosis in the hamster.
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PMID:Treatment of experimental silicosis with antifibrotic agents. 321 91

Gallium arsenide (GaAs) is an intermetallic compound that is recognized as a potential toxicological risk to workers occupationally exposed to its dust. Previous results have shown that rats intratracheally instilled with a fraction of GaAs particulates, characterized with a mean count diameter of 8.30 microns and a mean volume diameter of 12.67 microns, developed signs of systemic arsenic intoxication, pulmonary inflammation, and pneumocyte hyperplasia. The results of the present study confirm these findings and also show that a significantly smaller fraction of GaAs is a relatively more severe pneumotoxicant. Decreasing the particle mean count and mean volume diameter to 1.63 micron and 5.82 microns, respectively, increased the in vivo dissolution rate of GaAs, increased the severity of pulmonary lesions previously associated with GaAs exposure, and resulted in unique pathological sequelae in affected lung tissue. Pulmonary fibrosis, as indicated by analysis of lung 4-hydroxyproline content, was not considered statistically significant although histological examination of lung tissue revealed a mild fibrotic response. These results provide additional evidence that pulmonary exposure to respirable GaAs particulates is a potential health hazard in the semiconductor industry.
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PMID:Pulmonary clearance and toxicity of respirable gallium arsenide particulates intratracheally instilled into rats. 361 80

Effect of peplomycin sulfate (PLM) on pulmonary fibrosis was examined. Hydroxyproline, uronic acid, proline hydroxylase (EC 1.14.11.2) and glucosamine 6-phosphate synthetase (EC 2.6.1.16) in lungs of hamsters treated with PLM were studied and compared with those of hamsters treated with bleomycin (BLM). PLM, when administered intraperitoneally, one injection daily for 10 consecutive days, at either a high- (5 mg/kg) or low- (2.8 mg/kg) dosage-level, caused no significant increase of lung hydroxyproline and uronic acid as compared with controls. BLM on the other hand effected a significant increase in lung hydroxyproline on the high-dosage level (5 mg/kg) but not on the low-dosage level (2.8 mg/kg). In contrast, when administering PLM intratracheally, the concentrations of hydroxyproline in lungs increased 20% over the control levels. A transient increase of proline hydroxylase and glucosamine 6-phosphate synthetase also occurred shortly after the instillation. These increases were also observed in the corresponding groups treated with BLM, which confirmed the previous observations by other investigators. However, the magnitude of the increase was relatively lower in those values of PLM as compared with those of BLM. These data suggested that (1) PLM, when administered with multiple dosages intraperitoneally, showed no significant effect on the elevation of lung hydroxyproline; (2) PLM, when administered with a dose intratracheally, induced pulmonary fibrosis similar to that caused by BLM. However, the hydroxyproline accumulation in lungs of PLM-treated hamsters was less than in those of the BLM-treated; (3) The fibrotic effect on the lungs caused by either PLM or BLM was probably attributed to acceleration of the syntheses of collagen and acidic glycosaminoglycans.
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PMID:Peplomycin sulfate and pulmonary fibrosis: hydroxyproline, uronic acid, proline hydroxylase and glucosamine 6-phosphate synthetase in lungs of hamsters treated with peplomycin. 619 41

The purpose of this study was to examine whether development of pulmonary fibrosis in mice could be influenced by indomethacin, prednisolone or a proline analog. Pulmonary fibrosis was produced in mice treated with butylated hydroxytoluene (BHT) 400 mg/kg and immediately exposed to 80% oxygen for 3 days. This treatment regimen resulted in 47% mortality. Surviving mice exhibited significant accumulations of pulmonary collagen as evidenced by increases in total lung hydroxyproline levels. The administration of indomethacin (4 mg/kg/day) on days 1-6 after BHT decreased mortality to 14% and diminished the accumulation of collagen in lung tissue. Indomethacin also enhanced survival when administered on days 1-3 after BHT/O2 but had no effect on lung collagen levels. Treatment with indomethacin on days 4-6 after BHT had no beneficial effect. The administration of prednisolone (60 mg/kg/day) on days 1-3, 1-6, or 4-6 after BHT decreased mortality but had no effect on accumulation of lung collagen. Cis-4-hydroxyproline (400 mg/kg/day) also had no effect on pulmonary fibrosis but did enhance survival when given on days 1-3 after BHT. Administering prednisolone (60 mg/kg/day) on days 1-6 after BHT to mice left in room air produced significantly more pulmonary fibrosis than in BHT-treated mice given saline. These data support the use of the BHT/O2 model of pulmonary fibrosis for screening potential antifibrotic agents. The possibility that corticosteroid treatment may enhance pulmonary fibrosis in a damaged lung is also demonstrated.
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PMID:The effect of indomethacin, prednisolone and cis-4-hydroxyproline on pulmonary fibrosis produced by butylated hydroxytoluene and oxygen. 731 19

Taurine and niacin have been previously found to block the accumulation of collagen in lung in the multidose bleomycin hamster model of pulmonary fibrosis. Previous studies have found an increase in the pulmonary collagen cross-links dihydroxylysinonoroleucine (DHLNL) and hydroxypyridinium (OHP) in the single dose bleomycin rat model. In this study, we asked if taurine and niacin would block the increase in DHLNL and OHP in the multidose bleomycin hamster model of lung fibrosis. Hamsters were intratracheally instilled with three consecutive doses of saline or bleomycin sulfate 1 week apart (2.5, 2.0, 1.5 units/5 mL/kg). Animals were fed diet containing either 2.5% niacin and 2.5% taurine or control diet throughout the experiment. The four groups were saline-instilled with control diet (SCD), bleomycin instilled with control diet (BCD), bleomycin-instilled with taurine-niacin in diet (BTN), and saline-instilled with taurine-niacin in diet (STN). Animals were sacrificed at 1, 4, and 8 weeks after the last bleomycin instillation. Hydroxyproline per lung in the BCD group was significantly elevated by 38, 56, and 60% over the SCD group at 1, 4, and 8 weeks, respectively. There were no statistically significant differences among the four groups in DHLNL (mmole) per mole collagen at the 1 or 8 week time point. At four weeks, DHLNL was significantly elevated by 46.4% in the BCD group over the SCD group. The OHP (mmole) per mole of collagen at 1 and 4 weeks in the BCD group was not statistically different from the SCD group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dietary supplementation with taurine and niacin prevents the increase in lung collagen cross-links in the multidose bleomycin hamster model of pulmonary fibrosis. 752 Sep 44

Male and female Fischer-344 rats were exposed either to filtered air (controls) or to 0.12, 0.5, or 1.0 parts per million (ppm)* ozone for six hours per day, five days per week, for 20 months. We examined collagen deposition in lung tissue from these animals to determine whether or not chronic exposure of rats to ozone causes pulmonary fibrosis, as defined biochemically. Several techniques were used to study collagen deposition in the lungs of the animals. These methods included biochemical quantification by analysis of 4-hydroxyproline in lung tissue hydrolysates. The hydroxylysine-derived cross-links in mature collagen were quantified to estimate biochemically the excess of fibrotic collagen in the lung tissue. Biochemical analysis indicated excess collagen in the female rats exposed to 0.5 or 1.0 ppm ozone. Collagen in the lungs of the females also contained relatively more hydroxylysine-derived cross-links than did the lung collagen from age-matched control animals that had breathed only filtered air. Exposure of Fischer-344 rats for 20 months to 0.5 or 1.0 ppm ozone was associated with excess fibrotic lung collagen deposition as defined histologically. In female rats, exposure was also associated with excess deposition as determined biochemically. There was no indication of any significant changes in the lungs of any of the rats exposed to 0.12 ppm ozone, but the number of animals in this group was far too small to conclude whether this was a true no-observable-effect level. We conclude that chronic exposure of rats for 20 months to ozone at concentrations of 0.5 ppm or above for six hours per day, five days per week, causes mild to moderate lung fibrosis, as defined histologically and, in female rats, biochemically. The significance of these observations with regard to health risks to humans chronically inhaling ozone at ambient levels in polluted air remains to be determined.
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PMID:Consequences of prolonged inhalation of ozone on Fischer-344/N rats: collaborative studies. Part I: Content and cross-linking of lung collagen. 803 92

In the multiple-dose bleomycin-hamster model of pulmonary fibrosis, combined treatment with taurine and niacin blocks the increase in lung collagen deposition. We investigated the effects of taurine and niacin on lung lysyl oxidase and type I collagenase activities in this model. Hamsters were intratracheally instilled with three weekly doses of saline or bleomycin sulfate. Animals were fed either a diet containing 2.5% niacin and 2.5% taurine, or a control diet throughout the experiment. The four groups were saline-instilled with the control diet (BCD), bleomycin-instilled with the diet containing taurine and niacin (BTN), and saline-instilled with the diet containing taurine and niacin (STN). Animals were sacrificed at 1, 4, and 8 weeks after the last bleomycin instillation. Hydroxyproline per lung in the BCD group was significantly elevated by 38, 56, and 60% over the SCD group at 1, 4, and 8 weeks, respectively. Lysyl oxidase activity per lung in the BCD group was significantly elevated by 57.5 and 91.4% over the SCD controls at 1 and 4 week time periods, respectively. Type I collagenase activity per lung in the BCD group was significantly elevated by 65 and 80% over the SCD controls at 1 and 4 weeks, respectively. The combined treatment with taurine and niacin abolished the bleomycin-induced increases in the lung hydroxyproline content and lysyl oxidase and collagenase activities. It was postulated that one of the mechanisms for the antifibrotic effect of taurine and niacin may be the blockage of bleomycin-induced increases in the lung lysyl oxidase and collagenase activities.
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PMID:Mechanism of antifibrotic effect of taurine and niacin in the multidose bleomycin-hamster model of lung fibrosis: inhibition of lysyl oxidase and collagenase. 856 34


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