ascorbic-acid and Pulmonary-Fibrosis

Topics: Animals; Antidotes; Antineoplastic Agents; Ascorbic Acid; Bleomycin; Free Radicals; Male; Mice; Mice, Inbred C3H; Pulmonary Fibrosis; Recombinant Proteins; Superoxide Dismutase

to evaluate the effect of ascorbic acid and emoxypin on the efficiency of complex chemotherapy for infiltrative pulmonary tuberculosis.. One hundred patients with infiltrative pulmonary tuberculosis in a phase of decay were examined. The patients were divided into 3 groups. Group 1 received the standard therapy (n = 34); Groups 2 (n = 33) and 3 (n = 33) had additionally daily intravenous dropwise infusions of ascorbic acid (500 mg) (OAO "Novosibkhimpharm") or emoxypin (150 mg) (Moscow Endocrine Plant). The drugs were injected for 10 days. Therapeutic efficiency was evaluated during 12 months.. Additional use of ascorbic acid decreased the likelihood of progression of the disease to fibrocavernous tuberculosis and promotes a good completion of 12-month course of therapy providing small posttuberculous changes. The administration of emoxypin contributes to eradication of Mycobacterium tuberculosis, reduces the time of decay cavity closure and a need for surgical treatment of pulmonary tuberculosis.. The findings show it expedient to include ascorbic acid and emoxypin into the combined treatment regimen for infiltrative tuberculosis in a phase of decay.

Topics: Adult; Antitubercular Agents; Ascorbic Acid; Drug Therapy, Combination; Female; Humans; Male; Picolines; Pulmonary Circulation; Pulmonary Fibrosis; Tuberculosis, Pulmonary

The prognosis of patients with lung cancer accompanied by interstitial pneumonia is poorer than that of patients with lung cancer but without interstitial pneumonia. Moreover, the available therapeutic interventions for lung cancer patients with interstitial pneumonia are limited. Therefore, a new treatment strategy for these patients is required. The aim of the present study was to investigate the pathophysiological relationship between interstitial pneumonia and lung cancer and explore potential therapeutic agents.. A novel hybrid murine model of lung cancer with interstitial pneumonia was established via bleomycin-induced pulmonary fibrosis followed by orthotopic lung cancer cell transplantation into the lungs. Changes in tumor progression, lung fibrosis, RNA expression, cytokine levels, and tumor microenvironment in the lung cancer with interstitial pneumonia model were investigated, and therapeutic agents were examined. Additionally, clinical data and samples from patients with lung cancer accompanied by interstitial pneumonia were analyzed to explore the potential clinical significance of the findings.. In the lung cancer with interstitial pneumonia model, accelerated tumor growth was observed based on an altered tumor microenvironment. RNA sequencing analysis revealed upregulation of the hypoxia-inducible factor 1 signaling pathway. These findings were consistent with those obtained for human samples. Moreover, we explored whether ascorbic acid could be an alternative treatment for lung cancer with interstitial pneumonia to avoid the disadvantages of hypoxia-inducible factor 1 inhibitors. Ascorbic acid successfully downregulated the hypoxia-inducible factor 1 signaling pathway and inhibited tumor progression and lung fibrosis.. The hypoxia-inducible factor 1 pathway is critical in lung cancer with interstitial pneumonia and could be a therapeutic target for mitigating interstitial pneumonia-mediated lung cancer progression.

Topics: Animals; Ascorbic Acid; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Lung; Lung Diseases, Interstitial; Lung Neoplasms; Mice; Pneumonia; Pulmonary Fibrosis; Tumor Microenvironment

The aim of this study was to compare in vivo effect of five pharmacological options on inflammation and pulmonary fibrosis induced by paraquat.. 54 Wistar SPF rats were used. After 2 h post-intoxication with paraquat ion, groups of 9 animals were randomly assigned to (1) cyclophosphamide plus dexamethasone (2) low molecular weight heparin (3) unfractionated heparin (4) vitamin C every 24 h, (5) atorvastatin or (6) placebo with intraperitoneal saline. Lung inflammation, alveolar injury, hepatocyte damage, hepatic regeneration, acute tubular necrosis and kidney congestion were evaluated.. In the control group 100% of animals presented moderate and severe lung inflammation, while in the groups with atorvastatin and intratracheal heparin this proportion was lower (55.5%; CI 26.6-81.3%) (p = 0.025). A lower degree of moderate or severe hepatic regeneration was evident in the treatment groups with atorvastatin (p = 0.009). In this study was demonstrated that statins and heparin might have a protective effect in the paraquat-induced destructive phase. More evidence is needed to evaluated of dose-response effects of these drugs before to study in clinical trials.

Topics: Animals; Antioxidants; Ascorbic Acid; Atorvastatin; Cyclophosphamide; Dexamethasone; Drug Therapy; Drug Therapy, Combination; Heparin; Heparin, Low-Molecular-Weight; Lung; Paraquat; Pneumonia; Pulmonary Alveoli; Pulmonary Fibrosis; Rats, Wistar; Treatment Outcome

Paraquat (PQ) is one of the most widely employed herbicides that is used worldwide and it causes severe toxic effects in humans and animals. A PQ exposition can lead to pulmonary fibrosis (PF) and the mechanisms seem to be linked to oxidative stress, although other pathways have been suggested. Antioxidants can be useful as a therapy, although interventions with this kind of system are still controversial. Hence, this study has investigated the role of ascorbic acid (vitamin C) post-treatment on PQ-induced PF in male C57/BL6 mice. Pulmonary fibrosis was induced by a single PQ injection (10mg/kg; i.p.). The control group received a PQ vehicle. Seven days after the PQ or vehicle injections, the mice received vitamin C (150 mg/kg, ip, once a day) or the vehicle, over the following 7 days. Twenty-four hours after the last dose of vitamin C or the vehicle, the mice were euthanized and their bronchoalveolar lavage fluid (BALF) and their lungs were collected. The data obtained showed that vitamin C reduced the cellular recruitment, the secretion of IL-17 -a cytokine involved in neutrophils migration, TGF-β-a pro-fibrotic mediator and the collagen deposition. Moreover, vitamin C elevated the superoxide dismutase (SOD) and catalase levels, both antioxidant enzymes, but it did not alter the tracheal contractile response that was evoked by methacholine. Therefore, the researchers have highlighted the mechanisms of vitamin C as being non-invasive and have suggested it as a promising tool to treat lung fibrosis when it is induced by a PQ intoxication.

Topics: Animals; Antioxidants; Ascorbic Acid; Bronchoalveolar Lavage Fluid; Cell Count; Collagen; Cytokines; Lung; Lymphocytes; Macrophages; Male; Methacholine Chloride; Mice, Inbred C57BL; Neutrophils; Paraquat; Pulmonary Fibrosis

Radiation-Induced Lung Injury has 2 components: radiation pneumonitis and radiation fibrosis. The pulmonary fibrosis has no known efficient treatment. The purpose of this study was to study the relationship between the oxidant/antioxidant status and pulmonary fibrosis in rats having radiation induced pulmonary fibrosis and to study the antioxidant effects of pentoxifylline, vitamin E, and vitamin C in the treatment of pulmonary fibrosis.. The study rats were divided into 5 groups: Thoracic RT + vitamin E+ Pentoxifylline for group 1, Thoracic RT + vitamin C + Pentoxifylline for group 2, Thoracic RT + vitamin C + vitamin E + Pentoxifylline for group 3, and Thoracic RT + Pentoxifylline for group 4, and group 5 was the control group.. When groups are evaluated in pairs, significant differences between group 1 and 2, group 1 and 4, and group 1 and 5 were determined (p: 0.002, p: 0.002, p<0.001, respectively). No significant difference was determined between group 1 and 3 (p: 0.161). No significant difference was determined between group 2 and group 3, 4, and 5 (p: 0.105, p: 0.645, p: 0.234, respectively). There was no significant difference between group 4 and 5 (p: 0.645).. The combination of vitamin E and pentoxifylline is efficient in preventing radiation-induced lung fibrosis. The additional benefit of vitamin C, which is added to this combination to increase the antioxidant activity, cannot be shown. It would be useful to investigate the combination of vitamin E, pentoxifylline, and other non-enzymatic antioxidants.

Topics: Animals; Antioxidants; Ascorbic Acid; Histological Techniques; Pentoxifylline; Pulmonary Fibrosis; Radiation Injuries, Experimental; Radiotherapy; Rats; Statistics, Nonparametric; Stress, Physiological; Treatment Outcome; Vitamin E

The concentration of glutathione (GSH), the most abundant intracellular free thiol and an important antioxidant, is decreased in the lung in both fibrotic diseases and experimental fibrosis models. The underlying mechanisms and biological significance of GSH depletion, however, remain unclear. Transforming growth factor β (TGF-β) is the most potent and ubiquitous profibrogenic cytokine and its expression is increased in almost all fibrotic diseases. In this study, we show that increasing TGF-β1 expression in mouse lung to a level comparable to those found in lung fibrotic diseases by intranasal instillation of AdTGF-β1(223/225), an adenovirus expressing constitutively active TGF-β1, suppressed the expression of both catalytic and modifier subunits of glutamate-cysteine ligase (GCL), the rate-limiting enzyme in de novo GSH synthesis, decreased GSH concentration, and increased protein and lipid peroxidation in mouse lung. Furthermore, we show that increasing TGF-β1 expression activated JNK and induced activating transcription factor 3, a transcriptional repressor involved in the regulation of the catalytic subunit of GCL, in mouse lung. Control virus (AdDL70-3) had no significant effect on any of these parameters, compared to saline-treated control. Concurrent with GSH depletion, TGF-β1 induced lung epithelial apoptosis and robust pulmonary fibrosis. Importantly, lung GSH levels returned to normal, whereas fibrosis persisted at least 21 days after TGF-β1 instillation. Together, the data suggest that increased TGF-β1 expression may contribute to the GSH depletion observed in pulmonary fibrosis diseases and that GSH depletion may be an early event in, rather than a consequence of, fibrosis development.

Topics: Activating Transcription Factor 3; Animals; Apoptosis; Ascorbic Acid; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Epithelial Cells; Gene Expression Regulation, Enzymologic; Glutamate-Cysteine Ligase; Glutathione Disulfide; JNK Mitogen-Activated Protein Kinases; Lipid Peroxidation; Lung; Mice; Oxidation-Reduction; Oxidative Stress; Pulmonary Fibrosis; Respiratory Mucosa; Transcription, Genetic; Transforming Growth Factor beta1; Tyrosine

This study investigated the effectiveness of pirfenidone compared with antioxidants, in the prevention of pulmonary fibrosis and increasing the survival in acutely paraquat poisoned rats.. Five groups of ten rats were included in this study. Three groups were poisoned with intraperitoneal injection of 15 mg/kg paraquat. Among these poisoned groups, one group was treated with vitamin C (500 mg/kg, intraperitoneal), vitamin E (200 mg/kg, intraperitoneal) and N-acetylcysteine (250 mg/kg, intravenous); two others were treated with either normal saline or pirfenidone (200 mg/kg, intravenous); two groups were not poisoned and received normal saline or pirfenidone (200 mg/kg, intravenous). All injections except paraquat were repeated in four consecutive days. On the 15th day of study a semi-quantitative determination of lung fibrosis was done using Ashcroft staging criteria on the lung sections.. Pirfenidone decreased paraquat induced lung fibrosis (p < 0.001) while antioxidants did not decrease the lung fibrosis (p = 0.413). Life expectancy decreased in paraquat + normal saline (11 days, 95% CI 7.94-14.05) and paraquat + antioxidant (11 days, 95% CI 7.77-14.23) groups. The increase in the survival of rats in paraquat/pirfenidone group was insignificant (13.4 days, 95% CI 11.13-15.67).. This study showed that pirfenidone is able to decrease pulmonary fibrosis following paraquat poisoning in a rat model.

Topics: Acetylcysteine; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Ascorbic Acid; Disease Models, Animal; Herbicides; Injections, Intraperitoneal; Injections, Intravenous; Life Expectancy; Male; Paraquat; Pulmonary Fibrosis; Pyridones; Rats; Rats, Wistar; Survival Rate; Vitamin E

Topics: Acetylcysteine; Acute Kidney Injury; Adult; Ascorbic Acid; Charcoal; Chemical and Drug Induced Liver Injury; Combined Modality Therapy; Diuretics; Fatal Outcome; Furosemide; Gastric Lavage; Hemoperfusion; Humans; Immunosuppressive Agents; Male; Paraquat; Poisoning; Pulmonary Fibrosis; Respiration, Artificial; Respiratory Insufficiency; Rhabdomyolysis; Suicide, Attempted; Vitamin E

Increasing evidence indicates that disequilibrium of the alveolar oxidant-antioxidant balance may play a role in the pathogenesis of chronic fibrosing lung diseases. Excessive production of oxidants and a differential regulation of antioxidant enzymes have been described under these conditions. We characterized for the first time numerous nonenzymatic low-molecular-weight antioxidants in bronchoalveolar lavage fluids from patients with different forms of lung fibrosis initiated either by injury to the alveolar epithelium (idiopathic pulmonary fibrosis, IPF) or by inflammation (chronic sarcoidosis/hypersensitivity pneumonitis). Footprints of oxidative stress accompanied by an increase in the majority of antioxidants assessed were observed in all patient groups: elevated levels of uric acid, ascorbic acid, retinol, and alpha-tocopherol were noted, whereas glutathione levels were unchanged. The expression of Nrf2, an important redox-sensitive transcriptional regulator of antioxidants, was increased in IPF lungs. Our findings were corroborated in the bleomycin model of lung fibrosis where--aside from uric acid--nonenzymatic antioxidants were elevated during the fibrotic phase. In conclusion, alveolar levels of nonenzymatic antioxidants are elevated in fibrosing lung diseases, but are incapable of restoring oxidative balance. This increase may be part of an adaptive response to oxidative stress. However, a leakage from the blood may also contribute to our findings.

Topics: alpha-Tocopherol; Animals; Antioxidants; Ascorbic Acid; Blotting, Western; Bronchoalveolar Lavage Fluid; Glutathione; Humans; Idiopathic Pulmonary Fibrosis; Immunohistochemistry; Inflammation; Lung Diseases, Interstitial; Oxidative Stress; Pulmonary Fibrosis; Rabbits; Uric Acid; Vitamin A

Oxidative stress resulting from an imbalance between radical-generating and radical scavenging systems plays an important role in the pathogenesis of pulmonary fibrosis. Epigallocatechin-3-gallate (EGCG), a polyphenol and a major component of green tea, possess a potent antioxidant property. This study was designed to evaluate the potential antioxidative activity of EGCG in the plasma and lungs during bleomycin induced experimental pulmonary fibrosis. Intratracheal administration of bleomycin (6.5 U/kg body weight) to rats resulted in significant reduction of body weight, enzymic antioxidants (superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase) and non-enzymic antioxidants (reduced glutathione, vitamin C, vitamin E and vitamin A). Elevations in lung W/D (wet weight/dry weight) ratio, hydroxyproline content was observed with a synchronized increase in lipid peroxidation markers (thiobarbituric acid reactive substances and hydroperoxides). Intraperitoneal administration of EGCG at a dose of 20 mg/kg body weight significantly improved the body weight, enzymic and non enzymic antioxidants and considerably decreased the W/D ratio, hydroxyproline and lipid peroxidation marker levels. Histological observations also correlated with the biochemical parameters. Thus, this study confirms the beneficial use of EGCG in alleviating the oxidative stress induced during pulmonary fibrosis.

Topics: Animals; Antibiotics, Antineoplastic; Antioxidants; Ascorbic Acid; Bleomycin; Body Weight; Catechin; Glutathione; Injections, Intraperitoneal; Lung; Male; Organ Size; Pulmonary Fibrosis; Rats; Rats, Wistar; Thiobarbituric Acid Reactive Substances; Vitamin E

Many studies have shown that hexavalent chromium (Cr(6+)) compounds cause variety of toxicity, such as carcinogenic effects and pulmonary fibrosis. The aim of this study was to investigate the effect of vitamins C and E on hexavalent chromium-induced lung fibrosis in animal model. Rats weighing 180-210 g were used during the study. The negative control group received a single dose of 0.2 ml intratracheal normal saline. Other groups were given single intratracheal instillation of 50 mg/kg sodium dichromate in saline vehicle and then treated with either vitamin C or E orally. Vit C group treated with 75 mg/kg/day vit C. Vit E group treated with 20 mg/kg/day vit E. Vit C+E group treated with 75 mg/kg/day vit C + 20 mg/kg/day vit E. Three weeks after such treatments animals were killed, lungs were removed for histology and biochemical investigation. Collagen and hydroxyproline content of lung tissue were determined using spectrophotometric methods. Hexavalent chromium caused marked alveolar thickening associated with fibroblasts and myofibroblasts proliferation and collagen production in interstitial tissue leading to pulmonary fibrosis. Administration of vitamins C and E reduced the fibrotic damage in lung tissue. The combination of vit E and C had more pronounced effect. From this study it can be concluded that co-administration of vit C & E may significantly diminish the toxic effects of hexavalent chromium on lung.

Topics: Administration, Oral; Air Pollutants, Occupational; Animals; Antioxidants; Ascorbic Acid; Chromium; Collagen; Disease Models, Animal; Drug Therapy, Combination; Female; Fibroblasts; Male; Pulmonary Alveoli; Pulmonary Fibrosis; Rats; Rats, Sprague-Dawley; Vitamin E

A case of recovery from acute respiratory insufficiency due to paraquat is described. A 57-year-old farmer developed breathlessness, high fever and interstitial infiltrates in the upper and middle lung fields few days after percutaneous paraquat poisoning with rapid evolution to pulmonary fibrosis. Anti-inflammatory drugs and antioxidants, were administered to the patient, though with a delay, with some improvement; the patient survived despite residual lung fibrosis. Paraquat lung, as confirmed by this paper, is not invariably fatal.

Topics: Acute Disease; Agricultural Workers' Diseases; Ascorbic Acid; Humans; Male; Methylprednisolone; Middle Aged; Paraquat; Poisoning; Pulmonary Fibrosis; Skin Absorption; Vitamin E

Topics: Ascorbic Acid; Cell Line; Collagen; Fibroblasts; Gene Expression; Glutamate Decarboxylase; Humans; Interferon-gamma; Interleukin-1; Lung; Platelet-Derived Growth Factor; Pulmonary Fibrosis; RNA, Messenger; Transcription, Genetic; Transforming Growth Factor beta

The pulmonary fibrosis caused by peplomycin (PEP) was studied in terms of oxygen toxicity using ICR mice. When 16 micrograms of PEP was administered intratracheally in mice after exposure to the air containing 75% O2 for 10 days, the pulmonary fibrosis was completely suppressed, while when mice were exposed to 75% O2 after the administration of PEP, the fibrosis was much severe than that of mice raised in atmospheric air. In 50% O2, similar oxygen effect was also observed, but it was weaker than that in 75% O2. In 90% O2, the oxygen toxicity was observed in mice without administration of PEP. When mice were exposed to 75% O2, the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase, which are relevant to the detoxication of active oxygen species, were not increased in the lung, but the levels of reducing agents such as glutathione and ascorbic acid, and high molecular substances having 1O2-scavenging activity were enhanced. The results suggest that these materials have some roles to decrease the pulmonary fibrosis caused by PEP.

Topics: Animals; Antibiotics, Antineoplastic; Ascorbic Acid; Bleomycin; Catalase; Glutathione; Glutathione Peroxidase; Glutathione Reductase; Lung; Mice; Mice, Inbred ICR; Oxygen; Peplomycin; Pulmonary Fibrosis; Superoxide Dismutase

The clinical histories of 81 patients with hypersensitivity reactions to nitrofurantoin, 66 of whom had pulmonary reactions, were studied. Of all patients, 94% were women and of these, 43% were between 40 and 59 years of age. The nitrofurantoin preparation that contained vitamin c caused significantly fewer hypersensitivity reactions than the others. Acute pulmonary reactions appeared a mean of 8.7 days after the start of nitrofurantoin treatment. Typical for these were high fever, dyspnoea, cough, blood eosinophilia, bilateral pneumonic or pleuro-pneumonic infiltrations, a reduced transfer factor of the lung and, as revealed in pulmonary biopsy specimens, vasculitis, interstitial inflammation and alveolar exudation. Symptoms of subacute and chronic pulmonary reactions developed after at least 1 and 6 months of treatment, respectively. Findings of interest were anti-nuclear antibodies in serum, capillary sclerosis, interstitial fibrosis and inflammation in pulmonary tissue. Most patients with an acute pulmonary reaction recovered within 15 days, but in more than half of those with chronic reactions slight signs of pulmonary fibrosis persisted on follow-up. The findings suggest that the interstitial pulmonary changes caused by nitrofurantoin are largely the result of an Arthus-type immune complex-mediated reaction.

Topics: Acute Disease; Adult; Aged; Ascorbic Acid; Chronic Disease; Drug Combinations; Drug Hypersensitivity; Female; Humans; Male; Middle Aged; Nitrofurantoin; Pneumonia; Pulmonary Fibrosis

Topics: Animals; Ascorbic Acid; Collagen; Disease Models, Animal; Hydroxyproline; Iron; Ketoglutaric Acids; Mixed Function Oxygenases; Proline; Pulmonary Fibrosis; Rats; Silicosis

Topics: Ascorbic Acid; Humans; Pulmonary Fibrosis; Respiratory Therapy

Topics: Alanine Transaminase; Animals; Ascorbic Acid; Aspartate Aminotransferases; D-Alanine Transaminase; Guinea Pigs; Histocytochemistry; Lung; Pulmonary Fibrosis; Research; Silicosis

Topics: Ascorbic Acid; Bronchial Fistula; Bronchiectasis; Empyema; Empyema, Pleural; Humans; Lung Abscess; Lung Neoplasms; Oxytetracycline; Penicillins; Pneumonectomy; Postoperative Complications; Pulmonary Fibrosis; Punctures; Streptomycin; Thiamine