Exposure of the hydrophobic components of porcine lung surfactant to oxidant stress alters surface tension properties.

We have tested the hypothesis that oxidation of lung surfactant results in loss of surface tension lowering function. Porcine lung surfactant was exposed to conditions known to cause lipid peroxidation (0.2 mM FeCl2 + 0.1 mM H2O2 or 5 microM CuCl2). Lipid peroxidation was verified by detection of conjugated dienes, thiobarbituric acid reactive substances, fluorescent products, hydroxy alkenals, and loss of unsaturated fatty acids. Exposed samples had significantly diminished surface tension lowering ability in vitro as measured in a bubble surfactometer. Samples exposed to FeCl2 + H2O2 had significantly diminished surface tension lowering ability in vivo as indicated by their reduced ability to improve lung compliance of surfactant-deficient fetal rabbits. Oxidation of phospholipid mixtures with surface tension lowering activity and containing unsaturated acyl groups resulted in partial loss of activity as determined in vitro. These results suggest that the effect of oxidants on lung surfactant function is due, in part, to effects on the phospholipid components and that acute pulmonary inflammation accompanied by oxygen radical production may result in surfactant lipid peroxidation and loss of surface tension lowering function.     

Correction of respiratory organ impairment with Ural licorice preparations in chronic skin diseases

AIM: To study alterations in lipid peroxidation, antioxidant status of the lungs and immune state of the organism in some chronic diseases of the skin and potentialities of their correction with preparation produced of Ural licorice root. MATERIAL AND METHODS: Lipid peroxidation, antioxidant system parameters were examined in condensates of the expired air of 54 healthy subjects and 60 patients with chronic skin diseases. Immune status was studied in blood samples. The patients were given the drug made of Ural licorice root. RESULTS: The licorice-based drug normalized antioxidant defense and immune status. CONCLUSION: It was found possible to correct pulmonary and immune statuses of patients with some chronic skin diseases in polluted environment with a licorice drug.     

Surfactant protein D in human lung diseases

The lung is continuously exposed to inhaled pollutants, microbes and allergens. Therefore, the pulmonary immune system has to defend against harmful pathogens, while an inappropriate inflammatory response to harmless particles must be avoided. In the bronchoalveolar space this critical balance is maintained by innate immune proteins, termed surfactant proteins. Among these, surfactant protein D (SP-D) plays a central role in the pulmonary host defence and the modulation of allergic responses. Several human lung diseases are characterized by decreased levels of bronchoalveolar SP-D. Thus, recombinant SP-D has been proposed as a therapeutical option for cystic fibrosis, neonatal lung disease and smoking-induced emphysema. Furthermore, SP-D serum levels can be used as disease activity markers for interstitial lung diseases. This review illustrates the emerging role of SP-D translated from in vitro studies to human lung diseases.     

Respiratory manifestations of systemic disease. 3. Neurologic, skeletal, dermatologic, gynecologic, and gonadal diseases and disorders of pregnancy

Many nonpulmonary diseases may present with respiratory manifestations or may involve the lungs later in the disease course. The mechanisms by which such involvement occurs are almost as diverse as the diseases themselves and include the following. Hematogenous spread of disease is one of the most common mechanisms of lung involvement, for example, lung involvement by metastatic malignant disease. Cytotoxic factors from another anatomic location may be deposited in the alveolar basement membranes and cause pulmonary damage, for example, pulmonary hemorrhage associated with Goodpasture's syndrome. The pulmonary vasculature may prominently manifest generalized disease, as frequently occurs in Wegener's granulomatosis. Toxins accumulated as a result of disease in another organ system may damage the alveolar capillaries and result in pulmonary edema, as can occur in patients with severe azotemia due to renal failure. Depletion of lung surfactant as a consequence of disease in another organ system may produce alveolar collapse and respiratory failure; a disease that can have this effect is acute pancreatitis. The lungs may be the first organs to exhibit, through unknown mechanisms, underlying systemic diseases such as the collagenoses. Humoral factors released in another anatomic site may cause pulmonary problems; for example, bronchospasm may develop in patients with carcinoid of the intestine as a result of serotonin released by the tumor. Injury to another organ system can produce lung damage by complex mechanisms; an excellent example is the occasional development of neurogenic pulmonary edema in patients with trauma to the brain.(ABSTRACT TRUNCATED AT 250 WORDS)     

Decreased susceptibility of red blood cells to lipid peroxidation in patients with alcoholic liver cirrhosis

Red blood cells from alcoholics with and without liver cirrhosis and control subjects were examined for the susceptibility to lipid peroxidation. Red blood cells of patients with liver cirrhosis were found to be less sensitive to hydrogen peroxide-induced peroxidation measured by a new, reliable and sensitive method: the release of pentane during red blood cell lipid peroxidation. Changes of sensitivity to lipid peroxidation correlated with the severity of the liver malfunction, but not with abnormalities of the lipid composition of red cell membranes which are apparent in patients with liver disease. In alcoholics without liver cirrhosis, only minor changes in the susceptibility of red cells to peroxidation were observed.     

The effects of Oradexone and Ambroxol pretreatment of the oxidative sensitivity of the red blood cells in preterm infants

The antioxidant enzyme activities and lipid peroxidation in the red blood cells of cord blood were investigated and compared at different gestation times in preterm and full-term neonates, with and without pretreatment of the pregnant mothers with Oradexone (Dexamethasone) or Ambroxol. Administration of the two drugs not only stimulated the lung surfactant system, but also exerted favourable effects on the antioxidant enzyme activities while the lipid peroxidation was decreased.     

A micromodification of the method of determining the activity of processes of free radical oxidation]

A micromodification of the method for registration of bivalent iron ion-initiated chemiluminescence of the apo-beta-lipoprotein total fraction isolated from the blood serum is described. A significant elevation of lipid peroxide levels and of lipid ability to oxidation, paralleled by reduced levels of endogenous antioxidants as against the norm were revealed in the patients with acute disorders of brain circulation with the use of this method. Chemiluminescent studies of lipid peroxidation processes permit monitoring lipid peroxidation reactions and thus obtain a complex of parameters that characterize the status of these processes in the studied system. Due to its high sensitivity and specificity, chemiluminescent analysis may become one of the principal methods in studies of lipid peroxidation processes.     

Lipid peroxidation of the liver in liver disease

Material of puncture biopsy of the human liver left after morphological study was used to explore enzymatic and non-enzymatic lipid peroxidation, NADH-ferricyanide reductase activity, the content of triglycerides, cholesterol and protein. It was shown that the degree of lipid peroxidation varies considerably in different liver diseases. The highest degree of lipid peroxidation was discovered in patients with fibrosis accompanied by the symptoms of fatty dystrophy. It was established that the rate of peroxidation does not directly correlate with the level of liver lipid infiltration. It is concluded that NADH-ferricyanide reductase activity mirrors adequately the nature of a liver disease and can be used as a highly sensitive and very specific enzymatic test.     

Determination of the antioxidant properties of the blood and their diagnostic significance in the elderly]

Blood antioxidant system parameters were examined in elderly subjects. The authors have developed methods for measurements of catalase, superoxide dismutase, and lipid peroxidation products. They introduce a new factor 'F' that is supposed to characterize the blood antioxidant system; this factor is based on the values of catalase and superoxide dismutase activities and the intensity of lipid peroxidation. The authors come to a conclusion that the blood antioxidant and oxidant systems may be more accurately described with the use of this new factor F. In case of an abdominal tumor whole blood catalase level is elevated and superoxide dismutase activity significantly reduced. Factor F values were found extremely low before death, therefore this factor may be considered an important criterion of a critical state. The blood antioxidant parameters of patients with diabetes mellitus and essential hypertension did not much differ from those of age-matched healthy subjects.     

Immunomodulation by pulmonary surfactant

Canine pulmonary surfactant is recognized to modulate both T and B cell response in vitro. Because both responses involve cell proliferation, it has been suggested that surfactant interferes with the proliferation of lymphocytes. We herein report studies using human surfactant collected from amniotic fluid (HAFS). HAFS inhibited the proliferative response of human lymphocytes to antigen (PPD) and to allogeneic lymphocytes. Inhibition was linear within the dose range examined. Inhibition of the response to phytohemagglutinin was only evident when suboptimal doses of phytohemagglutinin were used. The effect of HAFS on the lysis of K562 human myeloid target cells by natural killer (NK) cells was also studied. Lysis in this system does not require proliferation. HAFS inhibited NK cell-induced lysis by 70% (250 micrograms HAFS per milliliter) to 95% (500 micrograms HAFS per milliliter). Inhibition was evident whether the cells were incubated with HAFS for 4 hours or for 18 hours. The NK suppressor activity was contained in the lipid fraction of HAFS, whereas the protein fraction revealed little activity. The washout experiments demonstrated that the action of HAFS was on NK cells and not on target cells. The immunomodulatory properties of surfactant affect NK cell activity and the proliferative response. Surfactant may protect the lungs from inappropriate immune reactions. Abnormalities of the lipid fraction of surfactant should be considered in studies of the mechanism of pulmonary diseases characterized by local pulmonary immune responses.     

Pulmonary surfactant: functions, abnormalities and therapeutic options

The first successful clinical pilot studies of surfactant replacement were published about 20 years ago as a logical extension of experimental studies showing beneficial effects in pre-term animals. The efficacy of this therapy for immature new-borns has been confirmed in various controlled trials and surfactant therapy is now part of the routine management of the infant respiratory distress syndrome. During the last decade there has been growing insight into the functional role of surfactant components and the mechanisms by which exogenous surfactant exerts its therapeutic effects on lung mechanics, gas exchange and host defence. Of particular interest in this context is the essential role that surfactant-associated proteins play in the surface tension-limiting ability of surfactant, as well as their contribution to pulmonary defence. Indications for surfactant replacement have widened in recent years and promising results have been obtained for adult conditions such as the acute respiratory distress syndrome (ARDS), pneumonia, chronic obstructive and allergic lung diseases. This review outlines the complexity of the surfactant system and describes its basic biophysics, physiology and biochemistry. Problems related to the development of exogenous surfactant preparations, the exploration of clinical targets for surfactant therapy and pathophysiological mechanisms interfering with surfactant function in various forms of lung disease will be discussed.     

Hyperoxia exposure impairs surfactant function and metabolism

OBJECTIVE: To evaluate the effects of hyperoxia exposure on lung function and the endogenous surfactant system in spontaneously breathing adult rats. DESIGN: Analysis of the pulmonary surfactant system isolated from adult rats following exposure to > 90% oxygen or room air for 48 or 72 hrs. SETTING: A basic science research laboratory in a university setting. SUBJECTS: Sixty pathogen-free Sprague-Dawley rats. INTERVENTIONS: Exposure to > 90% oxygen for 72 hrs. MEASUREMENTS AND MAIN RESULTS: Exposure to > 90% oxygen for 72 hrs resulted in significant lung dysfunction and an increase in neutrophils and total protein concentrations within the airspace compared with animals exposed to room air or 48 hrs of 90% oxygen exposure. Total alveolar surfactant and large aggregate pool sizes were increased after 72 hrs of hyperoxia compared with the other groups, and there was evidence of lipid peroxidation within these large aggregate subtractions. The biophysical function of large aggregate isolated from 72-hr hyperoxia-exposed animals was also impaired and converted into small aggregate forms faster than large aggregate from normoxia-exposed animals when assessed using in vitro surface area cycling techniques. CONCLUSIONS: Oxidative stress on the endogenous surfactant system may represent an important mechanism contributing to the surfactant dysfunction and abnormal surfactant metabolism associated with hyperoxia-induced lung injury.     

肺表面活性蛋白-D功能及其在肺部常见疾病中的研究进展

肺表面活性蛋白-D（SP-D）是凝集素家族糖蛋白,主要在肺部的肺泡Ⅱ型上皮细胞和无纤毛细支气管上皮细胞合成和分泌,储存在Clara细胞的分泌颗粒中。SP-D是表面结合蛋白之一,也是组成肺表面活性系统的一部分。SP-D除了有助于肺泡空间内表面活性剂池稳态外,还具有宿主防御和免疫调节功能。本文通过对近年来SP-D在肺部常见疾病中的部分相关研究进行总结,为众多肺部疾病,特别是肺部炎症性疾病潜在的治疗提供重要的方法理论基础。     

The metabolic basis of 3-methylindole-induced pneumotoxicity

3-Methylindole (3MI), an abnormal metabolite of tryptophan, causes acute pulmonary edema and emphysema. 3MI toxicity is species-, tissue- and cell-specific and is an excellent model for understanding the processes of chemically-induced lung injury. Experimental evidence showed that 3MI is metabolically activated by both microsomal cytochrome P-450-dependent mixed function oxidase (MFO) and prostaglandin H synthase (PHS) systems in the lung. Formation of a free radical intermediate during 3MI metabolism is the initial chemical event which is responsible for the pneumotoxicity. 3MI free radicals bind covalently to microsomal protein and induce lipid peroxidation. Microsomal enzymes which regulate the glycogen and phospholipid biosynthesis in the lung are altered during the cellular repair processes after 3MI-induced lung injury. Inhibition of cellular differentiation from Type II to Type I cells and impaired surfactant function may be crucial to the disease process.     

Oxidative stress and antioxidants in patients with cardiogenic shock complicating acute myocardial infarction

BACKGROUND: Lipid peroxidation and derived oxidized products are being intensively investigated because of their potential to cause injury and because of their pathogenic role in several diseases. The view that an excess of lipid peroxidation products is present and is relevant in the pathogenesis of cardiogenic shock-induced damage has still not received definitive support. METHODS: To evaluate the extent of lipid peroxidation, the status of enzymatic and nonenzymatic antioxidants in patients with cardiogenic shock that complicate acute myocardial infarction (AMI) and to compare with normal subjects. RESULTS: Compared with normal subjects, cardiogenic shock patients had higher malondialdehyde, conjugated dienes and reduced activities of erythrocyte antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and lower concentrations of reduced glutathione (GSH) in erythrocyte and in plasma GSH, vitamin C, vitamin E and in beta-carotene. CONCLUSIONS: Cardiogenic shock is associated with greater than normal lipid peroxidation and with an imbalance in antioxidants' status. These results indicate that low activities of SOD, CAT, GPx and low concentrations of GSH, vitamin C, vitamin E and beta-carotene in the circulation of patients with cardiogenic shock complicating AMI may be due to increased utilization to scavenge lipid peroxides. Decrease in plasma concentrations of GSH, vitamin E and beta-carotene seems to be responsible for the elevation of lipid peroxidation in cardiogenic shock complicating AMI compared with MI.     

The hydrocarbon breath test in the study of lipid peroxidation: principles and practice.

Lipid peroxidation has gained increasing interest in recent years as one of the more prominent features of free radical-induced damage in biology. The study of lipid peroxidation might increase our understanding of the etiology and pathophysiology of a great number of diseases. Ethane and pentane are among the numerous end-products of lipid peroxidation and although they represent only a small and possibly variable proportion of the total amount of peroxidized polyunsaturated fatty acids, their determination in head space or exhaled breath enables accurate assessment of oxidative stress both in vitro and in vivo. To date, the number of studies utilizing the hydrocarbon breath test as a marker of lipid peroxidation in humans is small. Technical difficulties are among the main reasons for the limited use of this method. An appropriate washout period, the use of the right materials, the scrupulous avoidance of air contamination, adequate preinjection concentrations of the samples, and a sensitive gas chromatographic technique enable the accurate and reproducible measurement of hydrocarbons in human breath. The hydrocarbon breath test provides a noninvasive and extremely sensitive instrument for the assessment of oxidative stress status in adults as well as in children.     

Clinical biological and genetic heterogeneity of the inborn errors of pulmonary surfactant metabolism.

Pulmonary surfactant is a multimolecular complex located at the air-water interface within the alveolus to which a range of physical (surface-active properties) and immune functions has been assigned. This complex consists of a surface-active lipid layer (consisting mainly of phospholipids), and of an aqueous subphase. From discrete surfactant sub-fractions one can isolate strongly hydrophobic surfactant proteins B (SP-B) and C (SP-C) as well as collectins SP-A and SP-D, which were shown to have specific structural, metabolic, or immune properties. Inborn or acquired abnormalities of the surfactant, qualitative or quantitative in nature, account for a number of human diseases. Beside hyaline membrane disease of the preterm neonate, a cluster of hereditary or acquired lung diseases has been characterized by periodic acid-Schiff-positive material filling the alveoli. From this heterogeneous nosologic group, at least two discrete entities presently emerge. The first is the SP-B deficiency, in which an essentially proteinaceous material is stored within the alveoli, and which represents an autosomal recessive Mendelian entity linked to the SFTPB gene (MIM 1786640). The disease usually generally entails neonatal respiratory distress with rapid fatal outcome, although partial or transient deficiencies have also been observed. The second is alveolar proteinosis, characterized by the storage of a mixed protein and lipid material, which constitutes a relatively heterogeneous clinical and biological syndrome, especially with regard to age at onset (from the neonate through to adulthood) as well as the severity of associated signs. Murine models, with a targeted mutation of the gene encoding granulocyte macrophage colony-stimulating factor (GM-CSF) (Csfgm) or the beta subunit of its receptor (II3rb1) support the hypothesis of an abnormality of surfactant turnover in which the alveolar macrophage is a key player. Apart from SP-B deficiency, in which a near-consensus diagnostic chart can be designed, the ascertainment of other abnormalities of surfactant metabolism is not straightforward. The disentanglement of this disease cluster is however essential to propose specific therapeutic procedures: repeated broncho-alveolar lavages, GM-CSF replacement, bone marrow grafting or lung transplantation.     

Surfactant proteins as genetic determinants of multifactorial pulmonary diseases

Surfactant proteins, SP-A, SP-B, SP-C and SP-D, play important roles in pulmonary surfactant function and metabolism. SP-A and SP-D, being members of the collectin family of proteins, also interact with pathogens and are involved in pulmonary host defense. Respiratory diseases are among the most common causes of death worldwide. Several life-threatening lung diseases, such as neonatal respiratory distress syndrome (RDS) and acute ROS (ARDS), are associated with impaired surfactant function. Allelic variations of the SP-A and SP-B genes have been shown to be important genetic determinants in individual susceptibility to RDS, which is a good general model for a multifactorial pulmonary disease resulting from complex interactions between several environmental and genetic factors. Because SP-A and SP-D act directly in the clearance of common lung pathogens, the genes encoding these proteins have been implicated as candidates in a few infectious diseases, including respiratory syncytial virus (RSV) infections and tuberculosis.     

State of pulmonary metabolism during radiotherapy of thoracic neoformations and possibilities of its correction

AIM: The study pulmonary metabolism by exhalation condensate of expired air (CEA) and ways of its correction in patients exposed to radiotherapy to the chest area. MATERIALS AND METHODS: 25 women aged 20 to 40 years with breast cancer stage I-II were divided into two groups: control group underwent conservative treatment without correction and the study group was given the extract of Ural licorice for 14 days. In CEA, lipid peroxidation enzymes and products of thiobarbituric acid were assayed. Biochemical examination of CEA was done by means of Cobas mira automatic analyzer. RESULTS: Administration of Ural licorice promoted inactivation of lipid peroxidation and maintenance of most of the biochemical parameters on the baseline level. This effect may be due to composition of the Ural licorice which contains antioxidants and stimulators of lung surfactant synthesis. CONCLUSION: Administration of Ural licorice extract seems promising for prevention of radiation complications in the lungs during radiotherapy to the chest area.