ascorbic-acid and Acute-Lung-Injury

Paraquat poisoning in Germany is rare. Because plasma levels do not necessarily match the ingested amount of paraquat, repeated measurement of plasma levels is imperative. There is a large potential in the prehospital phase to improve prognosis: further resorption must be terminated by rigorous charcoal administration and early tracheal intubation if necessary. Because paraquat can be resorbed by dermal contact, steps to ensure sufficient protection of emergency medical personnel must be taken.As soon as further resorption has been prevented sufficiently, forced diuresis, renal replacement therapy, and hemoperfusion can be of help, but still remain controversial. To reduce pulmonary fibrosis, inspiratory oxygen concentrations must be adjusted to the minimal amount needed to ensure satisfactory tissue oxygenation. Data supporting the advantageous use of cyclophosphamide combined with methylprednisolone for the treatment of pulmonary fibrosis were recently published. Since the toxic mechanism implies a mismatch of oxidants and anti-oxidants, co-administration of ascorbic acid and N-acetylcysteine are simple treatments with few side effects.

Topics: Acetylcysteine; Acute Kidney Injury; Acute Lung Injury; Adult; Antioxidants; Ascorbic Acid; Combined Modality Therapy; Conscious Sedation; Cooperative Behavior; Critical Care; Dose-Response Relationship, Drug; Emergency Medical Services; Esophagoscopy; Esophagus; Gastric Mucosa; Hemofiltration; Herbicides; Humans; Interdisciplinary Communication; Intermittent Positive-Pressure Ventilation; Intestinal Mucosa; Male; Metabolic Clearance Rate; Oxygen Inhalation Therapy; Paraquat; Prognosis; Pulmonary Edema; Suicide, Attempted

Pneumonia is a kind of inflammation, which can cause high morbidity and mortality, and the treatment of pneumonia has received widespread attention. Heme oxygenase-1 (HMOX1) is a cell protective enzyme and can generate an anti-inflammatory response. Here, we demonstrate that degradable carbon dots (from L-ascorbic acid, CDs-1) can up-regulate the expression of HMOX1 in animal cells and tissues, which has a therapeutic effect on LPS-induced acute lung injury in mice. It was confirmed from

Topics: Acute Lung Injury; Animals; Ascorbic Acid; Carbon; Female; Heme Oxygenase-1; Lipopolysaccharides; Membrane Proteins; Mice; Mice, Inbred BALB C; Particle Size; Quantum Dots; RAW 264.7 Cells; Reactive Oxygen Species; Surface Properties; Up-Regulation

Bacterial infections of the lungs and abdomen are among the most common causes of sepsis. Abdominal peritonitis often results in acute lung injury (ALI). Recent reports demonstrate a potential benefit of parenteral vitamin C [ascorbic acid (AscA)] in the pathogenesis of sepsis. Therefore we examined the mechanisms of vitamin C supplementation in the setting of abdominal peritonitis-mediated ALI. We hypothesized that vitamin C supplementation would protect lungs by restoring alveolar epithelial barrier integrity and preventing sepsis-associated coagulopathy. Male C57BL/6 mice were intraperitoneally injected with a fecal stem solution to induce abdominal peritonitis (FIP) 30 min prior to receiving either AscA (200 mg/kg) or dehydroascorbic acid (200 mg/kg). Variables examined included survival, extent of ALI, pulmonary inflammatory markers (myeloperoxidase, chemokines), bronchoalveolar epithelial permeability, alveolar fluid clearance, epithelial ion channel, and pump expression (aquaporin 5, cystic fibrosis transmembrane conductance regulator, epithelial sodium channel, and Na(+)-K(+)-ATPase), tight junction protein expression (claudins, occludins, zona occludens), cytoskeletal rearrangements (F-actin polymerization), and coagulation parameters (thromboelastography, pro- and anticoagulants, fibrinolysis mediators) of septic blood. FIP-mediated ALI was characterized by compromised lung epithelial permeability, reduced alveolar fluid clearance, pulmonary inflammation and neutrophil sequestration, coagulation abnormalities, and increased mortality. Parenteral vitamin C infusion protected mice from the deleterious consequences of sepsis by multiple mechanisms, including attenuation of the proinflammatory response, enhancement of epithelial barrier function, increasing alveolar fluid clearance, and prevention of sepsis-associated coagulation abnormalities. Parenteral vitamin C may potentially have a role in the management of sepsis and ALI associated with sepsis.

Topics: Abdomen; Acute Lung Injury; Animals; Ascorbic Acid; Biomarkers; Blood Coagulation; Bronchoalveolar Lavage; Cell Line; Cytoskeletal Proteins; Humans; Inflammation; Ion Channels; Ion Transport; Lung; Male; Mice; Mice, Inbred C57BL; Neutrophils; Peritonitis; Permeability; Pulmonary Alveoli; Respiratory Mucosa; Sepsis; Sodium-Potassium-Exchanging ATPase

Chlorine (Cl(2)) gas exposure poses an environmental and occupational hazard that frequently results in acute lung injury. There is no effective treatment. We assessed the efficacy of antioxidants, administered after exposure, in decreasing mortality and lung injury in C57BL/6 mice exposed to 600 ppm of Cl(2) for 45 minutes and returned to room air. Ascorbate and deferoxamine were administered intramuscularly every 12 hours and by nose-only inhalation every 24 hours for 3 days starting after 1 hour after exposure. Control mice were exposed to Cl(2) and treated with vehicle (saline or water). Mortality was reduced fourfold in the treatment group compared with the control group (22 versus 78%; P = 0.007). Surviving animals in the treatment group had significantly lower protein concentrations, cell counts, and epithelial cells in their bronchoalveolar lavage (BAL). Lung tissue ascorbate correlated inversely with BAL protein as well as with the number of neutrophils and epithelial cells. In addition, lipid peroxidation was reduced threefold in the BAL of mice treated with ascorbate and deferoxamine when compared with the control group. Administration of ascorbate and deferoxamine reduces mortality and decreases lung injury through reduction of alveolar-capillary permeability, inflammation, and epithelial sloughing and lipid peroxidation.

Topics: Acute Lung Injury; Animals; Antioxidants; Ascorbic Acid; Chemical Warfare Agents; Chlorine; Chromatography, High Pressure Liquid; Deferoxamine; Inhalation Exposure; Injections, Intramuscular; Lipid Peroxidation; Male; Mice; Mice, Inbred C57BL; Pneumonia; Siderophores; Survival Rate

Sepsis-induced lung injury is a persisting clinical problem with no direct therapy. Recent work suggests that intravenously infused ascorbic acid improves the circulatory dysfunction of sepsis. We used a model of endotoxin-induced acute lung injury to determine whether parenteral ascorbic acid modulates the dysregulated proinflammatory, procoagulant state that leads to lung injury.. C57BL/6 mice were exposed to lethal lipopolysaccharide doses (10 μg/g of body weight) to induce acute lung injury.. Laboratory investigation.. Wild-type C57BL/6 mice.. Ascorbic acid or its oxidized form (dehydroascorbic acid) was administered intraperitoneally at 200 mg/kg 30 mins after the lethal lipopolysaccharide dose.. We quantified survival, lung capillary leak, proinflammatory chemokine expression, and lung microvascular thrombosis. Lipopolysaccharide induced 100% lethality in mice within 28 hrs of exposure and in lung we observed intense neutrophil sequestration, loss of capillary barrier function, exuberant pulmonary inflammation, and extensive microthrombus formation. A time-delayed infusion protocol of both ascorbic acid and dehydroascorbic acid significantly prolonged survival. Both ascorbic acid and dehydroascorbic acid preserved lung architecture and barrier function while attenuating proinflammatory chemokine expression and microvascular thrombosis. Ascorbic acid and dehydroascorbic acid attenuated nuclear factor kappa B activation and normalized coagulation parameters.. Ascorbic acid administered in an interventional manner following lipopolysaccharide infusion attenuates proinflammatory, procoagulant states that induce lung vascular injury in an animal model of sepsis.

Topics: Acute Lung Injury; Animals; Antioxidants; Ascorbic Acid; Disease Models, Animal; Escherichia coli; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; Sepsis

The objective of this study was to determine if prolonged hyperoxia exposure would deplete antioxidants, resulting in excessive oxidative stress that would lead to oxidation of pulmonary surfactant and contribute to lung dysfunction. Rats were exposed to either hyperoxic (> 95% O(2)) or normoxic (21% O(2)) oxygen concentrations for 48 or 60 hours. Pulmonary compliance, inflammatory cells, and total protein levels were measured as indicators of lung injury. Bronchoalveolar lavage (BAL) samples were analyzed for surfactant composition, antioxidant content, and markers of oxidative stress. Antioxidants were also measured in lung tissue and plasma samples. Hyperoxia exposure for 60 hours resulted in increased protein and inflammatory cells in BAL, and lower pulmonary compliance, compared to all other groups. Total surfactant and surfactant large aggregates were increased following 48 hours of hyperoxia exposure, with a further increase following 60 hours. Animals exposed to 60 hours of hyperoxia also demonstrated lower ascorbate levels in lung tissue, increased lipid peroxides in BAL, and increased oxidation of phosphatidylglycerol species in surfactant. This study demonstrates that the balance of oxidant/antioxidant components is disrupted within the lung during periods of hyperoxia, and that although surfactant lipids may be susceptible to oxidative damage, they do not likely represent a major mechanism for the lung dysfunction observed.

Topics: Acute Lung Injury; Animals; Antioxidants; Ascorbic Acid; Biomarkers; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Hyperoxia; Lipid Peroxides; Lung; Lung Compliance; Male; Oxidative Stress; Phosphatidylcholines; Phosphatidylglycerols; Pulmonary Surfactants; Rats; Rats, Sprague-Dawley; Time Factors; Uric Acid