Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034063 (pulmonary edema)
 10,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxidative stress has been implicated in the adult respiratory distress syndrome (ARDS). In this study, we determined the levels of selected antioxidants in the plasma of 25 patients with ongoing ARDS and 16 healthy control subjects. We also examined these plasmas and pulmonary edema fluid of ARDS patients for lipid hydroperoxides. Both ascorbate and ubiquinol-10 concentrations in ARDS plasma were significantly lower than in normal plasma. alpha-Tocopherol concentrations, when standardized to total plasma cholesterol, were not lower in ARDS patients than in normal subjects. A pattern of antioxidant levels virtually identical to that observed in ARDS plasma was obtained after in vitro incubation of healthy plasma with stimulated polymorphonuclear leukocytes: very low ascorbate, decreased ubiquinol-10, and unchanged alpha-tocopherol concentrations. Nanomolar concentrations of lipid hydroperoxides were found in pulmonary edema fluid of ARDS patients, but not in plasma, nor in the plasma of healthy individuals, when a sensitive and selective chemiluminescence assay for hydroperoxides was used. ARDS patients also showed significant decreases in plasma levels of cholesterol esters in conjunction with discoidal high-density lipoprotein profiles, indicating a decrease in lecithin-cholesterol acyltransferase activity. We conclude that ARDS is associated with oxidative stress, possibly exerted by oxidants released from activated phagocytic leukocytes, and major changes in plasma cholesterol metabolism.
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PMID:Oxidative stress and abnormal cholesterol metabolism in patients with adult respiratory distress syndrome. 232 9

Endotoxin treatment in normal rats has a marked protective effect against O2 toxicity (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 47: 577-581, 1979 and 51: 577-583, 1981), and endotoxin's protective action is associated with stimulation of the lung's enzymatic antioxidant defense system (superoxide dismutase, catalase, glutathione peroxidase, and glucose-6-phosphate dehydrogenase). Vitamin E-deficient animals are especially sensitive to hyperoxidant stresses, including pulmonary O2 toxicity. In these studies we tested whether endotoxin could reverse the increased susceptibility of vitamin E-deficient rats to hyperoxic challenge. We found that untreated vitamin E-deficient rats do succumb more readily to O2 toxicity [0/11 alive at 72 h in greater than 95% O2, lethal time for 50% of the animals (LT50) = 50 h] than rats fed a regular diet (4/14 alive, LT50 = 69 h). In contrast, 15 of 16 vitamin E-deficient rats treated with endotoxin survived the same O2 exposures (P less than 0.001) and showed significantly reduced pulmonary edema compared with the other groups. The endotoxin-treated vitamin E-deficient group was also the only one to demonstrate significant elevations of all the antioxidant enzymes during O2 exposure, suggesting that the antioxidant enzyme defenses of the lung have a more primary and important role in prevention of O2-induced lung injury than the lipid-associated antioxidant, vitamin E.
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PMID:Endotoxin treatment protects vitamin E-deficient rats from pulmonary O2 toxicity. 638 80

Reactive oxygen species are known to play a key role in the development of acute lung injury, and such injury can be alleviated by pretreating the lung with a suitable antioxidant preparation. In this study, we evaluated and compared the antioxidant efficacy of two liposomal preparations: liposomes containing only alpha-tocopherol versus bifunctional liposomes containing both alpha-tocopherol and glutathione (GSH). alpha-Tocopherol liposomes (2 mg alpha-tocopherol/animal) or liposomes containing both alpha-tocopherol and GSH (2 mg alpha-tocopherol and 10 mumol GSH/animal) were intratracheally instilled into the lungs of rats 30 min prior to a challenge with paraquat dichloride (30 mg/kg, i.p.); animals were killed 24 hr post-paraquat challenge. Lungs of paraquat-challenged animals were damaged extensively as evidenced by increases in lung weight, indicative of edema, and decreases in lung activities of angiotensin converting enzyme (ACE) and alkaline phosphatase (AKP), indicative of endothelial and alveolar type II epithelial cell injuries, respectively. While the pretreatment of rats with alpha-tocopherol liposomes or liposomes containing both alpha-tocopherol and GSH significantly attenuated paraquat-induced changes in lung ACE activity to more or less the same extent, the bifunctional liposomal preparation conferred additional protection to alveolar type II epithelial cells, as evidenced by a significantly higher pulmonary AKP activity. Our results also showed that both liposomal preparations failed to ameliorate paraquat-induced lung edema despite a significant protection of pulmonary endothelial cells, suggesting that paraquat-induced edema formation may be independent of endothelial cell damage. In conclusion, liposome-associated antioxidants can protect the lung against an oxidant challenge, and the extent of protection appears to be related to the characteristics of each antioxidant formulation.
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PMID:Alleviation of paraquat-induced lung injury by pretreatment with bifunctional liposomes containing alpha-tocopherol and glutathione. 893 65

Phosgene, widely used in industrial processes, can cause life-threatening pulmonary edema and acute lung injury. One mechanism of protection against phosgene-induced lung injury may involve the use of antioxidants. The present study focused on dietary supplementation in mice using n-propyl gallate (nPG)--a gallate acid ester compound used in food preservation--and vitamin E. Five groups of male mice were studied: group 1, control-fed with Purina rodent chow 5002; group 2, fed 0.75% nPG (w/w) in 5002; group 3, fed 1.5% nPG (w/w) in 5002; group 4 fed 1% (w/w) vitamin E in 5002; and group 5, fed 2% (w/w) vitamin E also in 5002. Mice were fed for 23 days. On day 23 mice were exposed to 32 mg m-3 (8 ppm) phosgene for 20 min (640 mg. min m-3) in a whole-body exposure chamber. Survival rates were determined at 12 and 24 h. In mice that died within 12 h, the lungs were removed and lung wet weights, dry weights, wet/dry weight ratios, lipid peroxidation (thiobarbituric acid reactive substances, TBARS) and glutathione (GSH) were assessed. Vitamin E had no positive effect on any outcome measured. There was no significant difference between 1.5% nPG and any parameter measured or survival rate compared with 5002 + phosgene. However, dietary treatment with 0.75% nPG significantly increased survival rate (P </= 0.002) and lowered TBARS (P </= 0.05) compared with 5002 + phosgene at 12 h after exposure. Mice fed 0.75% nPG had a lower wet/dry wt ratio compared with those fed 1.5% nPG and a significantly increased lung tissue GSH 36%, compared with the 5002 + phosgene group. In conclusion, dietary treatment with a low level of the antioxidant nPG protected mice by decreasing lipid peroxidation and increasing lung tissue GSH. The higher level of nPG and both levels of vitamin E diets were ineffective, suggesting that a ceiling threshold level of antioxidants in lung tissue is required for survival against phosgene-induced lung injury. Published in 2001 by John Wiley & Sons, Ltd.
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PMID:Effect of dietary treatment with n-propyl gallate or vitamin E on the survival of mice exposed to phosgene. 1118 Feb 78

We investigated the pharmacologic effects of the antioxidant Vitamin E (alpha-tocopherol [alpha-toc]) in airway inflammation induced by inhaled endotoxin. A preparation of alpha-toc incorporated in liposomes was administered intraperitoneally in mice 1 h after exposure of aerosolized endotoxin. Injection of 50 mg alpha-toc/kg significantly decreased the number of neutrophils in airspaces and prevented lung injury, monitored both as decreased lactate dehydrogenase activity in airways and reduced lung edema when compared with animals treated with plain liposomes. Immunofluorescence staining of lung tissue revealed that treatment with alpha-toc decreased the number of neutrophils in lung interstitium, whereas the number in lung blood vessels and peripheral blood did not differ between mice treated with alpha-toc and control mice. Our results indicate that alpha-toc downmodulates the migration of neutrophils across the endothelial barrier, but in contrast to strong anti-inflammatory drugs such as corticosteroids, without inhibition of transcription factors involved in the early inflammatory response (nuclear factor-kappaB/activator protein-1). Neither was the endotoxin-induced expression of proinflammatory cytokines in lung tissue downregulated. Treatment with a combination of alpha-toc and a suboptimal dose of 0.5 mg/kg dexamethasone enhanced the effect, suggesting that alpha-toc, in combination with low doses of corticosteroids, might be effective for therapeutic treatment of acute lung injury.
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PMID:Vitamin E reduces transendothelial migration of neutrophils and prevents lung injury in endotoxin-induced airway inflammation. 1254 Apr 87