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

We examined the effect of free radicals on lung defense mechanism in bleomycin (BLM)-induced pulmonary fibrosis in hamsters. The concentration of vitamin E (VE) in the lung tissue increased significantly after intratracheal BLM administration. VE deficient hamsters showed increased lipid peroxide values in the lung tissue at a very early stage after BLM treatment. This was followed by decreased superoxide dismutase activities in the lung tissue. The results indicate that; 1) VE appears to be necessary for the prevention of lipid peroxidation in BLM-induced oxidant lung injury, 2) VE deficiency produces a large number of free radicals at the early stage after BLM treatment, and might induce protease-antiprotease imbalance within the lung, which probably causes an emphysematous change in the BLM-treated lung at a late stage after BLM administration.
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PMID:[Effects of vitamin E deficiency on bleomycin-induced pulmonary fibrosis in hamsters]. 169 85

The effects of vitamin E deficiency on bleomycin (BLM)-induced pulmonary fibrosis have been studied by analyses of pressure volume (PV) curves and morphological examinations. Golden hamsters were divided into groups on a control diet (group C), vitamin E-deficient diet (E), control diet with BLM treatment (CB), and vitamin E-deficient diet with BLM treatment (EB). Group EB showed PV curves shifted downward and to the right soon after BLM administration (10 days) and gradually shifted upward and to the left compared to group CB in the later period (30 and 60 days after BLM treatment). Histologically group EB was characterized by relatively severe interstitial pneumonitis in the early stages. In later stages, emphysematous changes were induced in combination with a lesser degree of fibrosis in group EB. Mean thickness of the alveolar wall of group CB was larger than group C while that of group EB was smaller at 30 days after BLM treatment. These results indicate that, with BLM treatment, vitamin E-deficient hamsters show increased distensibility on the PV curve and emphysematous changes mixed with focal fibrosis on morphological examination. This means that by adding other modulating factors, such as vitamin E deficiency, BLM, an agent known to produce pulmonary fibrosis, acts to induce an emphysematous lesion in the lung. Although pulmonary fibrosis and emphysema have been considered to be final and different forms of parenchymal injury, each may proceed to the other under the influence of some modulating factors.
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PMID:Effects of vitamin E deficiency on bleomycin-induced pulmonary fibrosis in the hamster. 245 80

Lung inflammatory cells in idiopathic pulmonary fibrosis (IPF) is characterized by an increased spontaneous production of oxidants. This suggests that the oxidants may play a role in causing the epithelial cell injury in the early stage of IPF. Bleomycin (BLM) induces pulmonary fibrosis by oxidant production. We tested the hypothesis that a dietary supplement of vitamin E (VE) may protect against, and its deficiency may exacerbate, BLM-induced pulmonary fibrosis. Because the hamster is known to be the best model among animals studied mimicking human lung antioxidant enzyme activities, Syrian Golden hamsters were used in this study. In dietary VE supplement and BLM treated group (Ead.B), mean serum VE concentration increased by about 3 times that of control (C) and the BLM treated group (CB). Despite the remarkably high VE content, no significant difference was found between CB and Ead.B for pressure-volume (PV) curves and morphological data. In BLM treated with dietary VE deficient group (Ede.B), serum VE concentrations markedly decreased on all experimental days compared with other groups. Mechanical properties in P-V curves of Ede.B showed most less distensible characteristics in early stage and most distensible characteristics in later stage. These emphysematous changes observed in P-V curves in the later stage of Ede.B, coincided with the morphological observations. In the early stage of BLM treatment, lipid peroxide concentrations in the lung tissue were significantly higher in Ede.B compared with other groups. It was concluded that a dietary supplement of VE cannot protect against BLM-induced pulmonary fibrosis, and a dietary VE deficiency exacerbates BLM lung injury to produce on emphysema in the hamster.
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PMID:[Pulmonary fibrosis and antioxidant agents]. 247 76

The major cause of death in paraquat poisoning is a rapidly progressive respiratory failure due to an oxidative insult to the alveolar epithelium with subsequent fulminant obliterating fibrosis. The present study evaluates the effectiveness of vitamin E in combination with colchicine in ameliorating paraquat lung injuries in rats. Vitamin E is a biologic antioxidant interfering with lipid peroxidation, and colchicine reduces collagen synthesis which is significantly augmented in pulmonary fibrosis. Eight normal rats were given a single i.p. dose of paraquat at 15 mg/kg. The treated group included eight animals that received, in addition to i.p. paraquat (15 mg/kg), daily doses of vitamin E (100 mg/kg i.p.) and colchicine (0.1 mg/kg i.p.). All the rats in the paraquat group died within 42 to 96 h, six of them within 60 h, following severe respiratory failure. The treated rats developed a somewhat milder form of respiratory insufficiency, six of them dying within 48 to 72 h. Less severe intra-alveolar hemorrhages were observed in this group. Two rats survived, and these had only mild emphysema on autopsy at 21 days. Our preliminary results suggest that the combination of vitamin E with colchicine may be effective in ameliorating lung injuries caused by paraquat, and warrant further studies.
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PMID:Effectiveness of vitamin E and colchicine in amelioration of paraquat lung injuries using an experimental model. 270 31

In patients with subacute toxic reactions from paraquat poisoning (death within 11 to 41 days), the extent of lipid peroxidation, expressed as serum malondialdehyde level, was 2.7-fold higher (12.33 +/- 4.42 nmole/mL) before pulmonary fibrosis than that in normal controls (4.55 +/- 1.23 nmole/mL). The extent of lipid peroxidation in patients with acute toxic reactions (death within one to three days) was not elevated; these patients died of pulmonary edema and hemorrhage (acute respiratory distress), liver failure, renal failure, and adrenal necrosis. Remarkable high levels of paraquat (greater than 5 mg/L) were found in the urine, serum, and tissues of patients with acute toxic reactions; a small amount of paraquat was found in the serum or urine of patients with subacute toxic reactions five to 11 days after ingestion. Patients who survived had no elevation in lipid peroxidation. Administration of vitamin E (100 to 4,000 mg/day from the first hospital day) had no effect on survival.
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PMID:Further studies of lipid peroxidation in human paraquat poisoning. 396 49

It has been discovered in rat experiments that the diet containing an additional amount of methionine and pyridoxine and optimal quantity of fat favoured to a certain degree the retardation of the development of pulmonary fibrosis and reduced the disorders in metabolism of vitamins, characteristic for animals with experimental anthracosis. On the contrary, introduction of an additional amount of retinol into the above complex aggravated the development of pulmonary fibrosis and alterations in vitamin metabolism. At the same time the negative manifestations seen in the animals with experimental anthracosis were removed to a certain measure by administering additional doses of vitamin E.
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PMID:[Effect of methionine, retinol, tocopherol and pyridoxine on fibrogenesis in the lungs and vitamin metabolism in rats in an anthracosis model]. 647 21

A 20-year-old man ingested approximately 15 to 20 mL of a 24% solution of paraquat. Acute renal and liver failure developed. The patient began undergoing hemodialysis and receiving vitamin E, but he died of pulmonary fibrosis the 27th day after the ingestion. During a two-week period of observation, evidence of lipid peroxidation in his serum was noted by determining malondialdehyde levels. Guinea pigs exposed to paraquat showed similar patterns of malondialdehyde presence in plasma. These results indicate that increased serum or plasma levels of lipid peroxide occurring in paraquat poisoning might reflect production of highly reactive oxygen free radicals and that, possibly, levels of lipid peroxides could serve as indicators of the efficacy of therapy directed toward scavenging free radicals.
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PMID:Acceleration of lipid peroxidation in human paraquat poisoning. 725 76

Bleomycin is a widely used antineoplastic drug which produces dose- and time-dependent interstitial pulmonary fibrosis in humans. The mechanism of bleomycin-induced lung injury is not well understood. However, current data show that bleomycin can generate reactive oxygen species such as superoxide and hydroxyl radicals. The antioxidant role of vitamin E in biological systems is well known. We investigated the effect of vitamin E on bleomycin-induced lung fibrosis in mice biochemically and histologically. Animals were divided into four groups: control, saline + vitamin E (S/Vit E), bleomycin + saline (Bleo/S) and bleomycin + vitamin E (Bleo/Vit E). Bleomycin was administered subcutaneously at a dose of 10 mg/kg in Bleo/S and Bleo/Vit E groups, and vitamin E was administered intraperitoneally at a dose of 15 mg/animal in S/Vit E and Bleo/Vit E groups twice weekly for 4 weeks. The control group received saline. As a marker of collagen amount or fibrosis in lung tissue, hydroxyproline and soluble protein content were measured and hydroxyproline/soluble protein ratio per gram wet lung tissue was calculated. For hydroxyproline and protein determinations, and histologic examination of lung tissue, 6 mice from the control and S/Vit E groups and 7 mice from the Bleo/S and Bleo/Vit E groups were killed at at 4, 6 and 8 weeks after administration of bleomycin. The mean hydroxyproline/soluble protein ratio of the Bleo/Vit E group was significantly lower than that of the Bleo/S group and significantly higher than those of the control and S/Vit E groups at 6 and 8 weeks (p < 0.05). Parallel with the biochemical findings, the grade of the histological lesions in the Bleo/Vit E group was lower than that in the Bleo/S group, but higher than those of the S/Vit E and control groups (p < 0.05). These results suggest that a high dose of vitamin E considerably reduces the fibrotic effect of bleomycin on lung tissue in mice.
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PMID:Vitamin E reduces bleomycin-induced lung fibrosis in mice: biochemical and morphological studies. 867 19

Amiodarone (AM) is a potent and efficacious antidysrhythmic agent that can cause potentially life-threatening pulmonary fibrosis. Vitamin E has been demonstrated to decrease AM-induced pulmonary fibrosis in vivo in hamsters. In the present in vitro study, we investigated the effects of vitamin E on cell death induced by AM and its primary metabolite, N-desethylamiodarone (DEA), in freshly isolated hamster lung cells. Following incubation for 24 or 36 h, 300 microM vitamin E decreased (P<0.05) 100 microM AM-induced cytotoxicity (0.5% trypan blue uptake) in alveolar macrophages by 11.7+/-3% or 21.4+/-12%, respectively, but did not decrease cytotoxicity in fractions enriched with alveolar type II cells or non-ciliated bronchiolar epithelial (Clara cells) or in isolated unseparated cells (cell digest). Vitamin E had no effect on 50 microM DEA-induced cytotoxicity. Vitamin E did not alter cellular levels of AM or DEA in any cell fraction. Lipid peroxidation (assessed by isoprostane formation) was increased (P<0.05) in cell digest, alveolar type II cell and Clara cell enriched fractions incubated with 500 microM carbon tetrachloride (CCl(4)) for 4 h but not in enriched fractions of cells exposed to 100 microM AM or 50 microM DEA. No AM-induced loss of viability was observed at this time point, but DEA decreased (P<0.05) Clara cell viability by approximately 25%. These results demonstrate cell type selective protection against AM-induced cytotoxicity by vitamin E, and suggest that lipid peroxidation does not initiate AM- or DEA-induced cytotoxicity in isolated hamster lung cells.
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PMID:Effects of vitamin E on cytotoxicity of amiodarone and N-desethylamiodarone in isolated hamster lung cells. 1154 7

Amiodarone (AM) is an efficacious antidysrhythmic agent that can cause numerous adverse effects, including potentially life-threatening pulmonary fibrosis. The current study was undertaken to investigate potential protective mechanisms of vitamin E against AM-induced pulmonary toxicity (AIPT) in the hamster. Three weeks after intratracheal administration of AM (1.83 micromol), increased pulmonary hydroxyproline content and histological damage were observed, indicative of fibrosis. These effects were preceded by increased pulmonary levels of transforming growth factor (TGF)-beta1 mRNA at 1 week post-AM, which remained elevated 3 weeks post-AM. Dietary supplementation with vitamin E resulted in rapid pulmonary accumulation of the vitamin, and prevention of AM-induced increases in TGF-beta1, hydroxyproline, and histological damage. Although dietary supplementation also markedly elevated lung mitochondrial vitamin E content, it did not attenuate AM-induced inhibition of mitochondrial respiration or disruption of mitochondrial membrane potential in vitro, or lung mitochondrial respiratory inhibition resulting from in vivo AM administration. These results suggest that vitamin E reduces the extent of pulmonary damage after AM administration via down-regulating TGF-beta1 overexpression but that it does not modify AM-induced mitochondrial dysfunction, a potential initiating event in AIPT.
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PMID:Attenuation of amiodarone-induced pulmonary fibrosis by vitamin E is associated with suppression of transforming growth factor-beta1 gene expression but not prevention of mitochondrial dysfunction. 1249 Jun 2


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