Effect of lithium oxybutyrate on lipid metabolic changes in pituitrin-induced pulmonary edema

The experiments on white rats have confirmed that the development of lung edema following pituitrin infusion is characterized by considerable changes in phospholipid and cholesterol lung metabolism and cholesterol blood metabolism. Lithium hydroxybutyrate preinjection at a dose of 400 mg/kg prevented a decrease in cholesterol lung content and an increase in cholesterol blood plasma level which was accompanied by less prominent lung edema.     

Phospholipids of normal and experimentally injured spinal cord of the miniature pig

Experimental spinal cord trauma was produced in 3-month-old SS-1 minature pigs by dropping a 25 g weight from a height of 20 cm upon the exposed spinal cord. The histological lesion consisted of edema and hemorrhage. Phospholipid concentration and composition, cholesterol concentration and phospholipid fatty acid composition were determined in whole spinal cord 3 hours after injury, and in spinal cord myelin 5 hours after injury. Three hours after injury phospholipid and cholesterol concentration were decreased by about 14% in the whole spinal cord. Trauma had no effect on the phospholipid composition of whole spinal cord and myelin. Fatty acid composition of myelin also did not change after injury, and changed very slightly in the whole spinal cord. It is concluded that edema following spinal cord trauma is much more extensive than previously assumed. Furthermore, peroxidation of membrane lipid fatty acids does not appear to be a significant factor in spinal cord pathology 3 hours after injury.     

Membrane regulation of liver and lung microsomes under low oxygen tension

A highly monitorized animal model has been developed for the study of the influence of low oxygen tension on lipid composition, microviscosity and regulation of enzyme activities involved in the phospholipid synthesis of hepatic and pulmonary microsomes. Microviscosity decreased in liver microsomes whereas no difference was shown in that of microsomal membrane core of hypoxemic lung. Nevertheless, phospholipid and cholesterol content of both liver and lung membranes changed significantly. Microsomal membranes of hypoxemic liver increased the unsaturation degree of fatty acids, whereas hypoxemic lung membranes become more saturated, mainly due to the increase of palmitic acid. The adaptive response of lung was confirmed by the high increase of the deacylation-reacylation mechanism.     

Composition,biophysical properties,and morphometry of plasma membranes in pulmonary interstitial edema

We evaluated the changes in plasma membrane composition, biophysical properties, and morphology of pulmonary endothelial cells in anesthetized rabbits receiving 0.5 ml. kg(-1). min(-1) saline infusion for 180 min, causing mild interstitial edema. Plasma membrane fractions were obtained from lung homogenates with gradient centrifugation, allowing a sixfold enrichment in caveolin-1. In edematous lungs, cholesterol content and phospholipidic phosphorus increased by 15 and 40%, respectively. These data correlated with morphometric analysis of lungs fixed in situ by vascular perfusion with 2.5% glutaraldehyde, suggesting a relative increase in surface of luminal to interstitial front of the capillary endothelial cells, due to a convoluted luminal profile. In edematous lungs, the fraction of double-bound fatty acids increased in membrane lipids; moreover, the phosphatidylcholine/phosphatidylethanolamine and the cholesterol/phospholipid ratios decreased. These changes were consistent with the increase in fluorescence anisotropy of plasma membrane, indicating an increase in its fluidity. Data suggest that mechanical stimuli elicited by a modest (approximately 4%) increase in extravascular water cause marked changes in plasma membranes that may be of relevance in signal transduction and endothelial cell activation.     

LXR-induced reverse cholesterol transport in human airway smooth muscle is mediated exclusively by ABCA1

The association of hypercholesterolemia and obesity with airway hyperresponsiveness has drawn increasing attention to the potential role of cholesterol and lipid homeostasis in lung physiology and in chronic pulmonary diseases such as asthma. We have recently shown that activation of the nuclear hormone receptor liver X receptor (LXR) stimulates cholesterol efflux in human airway smooth muscle (hASM) cells and induces expression of the ATP-binding cassette (ABC) transporters ABCA1 and ABCG1, members of a family of proteins that mediate reverse cholesterol and phospholipid transport. We show here that ABCA1 is responsible for all LXR-mediated cholesterol and phospholipid efflux to both apolipoprotein AI and high-density lipoprotein acceptors. In contrast, ABCG1 does not appear to be required for this process. Moreover, we show that hASM cells respond to increased levels of cholesterol by inducing expression of ABCA1 and ABCG1 transporters, a process that is dependent on LXR expression. These findings establish a critical role for ABCA1 in reverse cholesterol and phospholipid transport in airway smooth muscle cells and suggest that dysregulation of cholesterol homeostasis in these cells may be important in the pathogenesis of diseases such as asthma.     

Regional extravascular density of the lung in patients with acute pulmonary edema

The regional distribution of extravascular lung density (lung tissue and interstitial or alveolar fluid per unit thoracic volume) and fractional pulmonary blood volume (volume of blood per unit thoracic volume) was measured in five patients with acute interstitial pulmonary edema and two patients with acute alveolar edema. We found a uniform increase in extravascular lung density in the patients with acute interstitial edema but a preferentially dependent distribution in the patients with alveolar edema. Fractional blood volume had an abnormally uniform distribution in patients with interstitial edema. In alveolar edema, there was marked redistribution of blood volume away from severely edematous regions. The results are in agreement with previous experimental work with animal models. The distribution of extravascular lung density and fractional blood volume in subjects with acute interstitial edema is, however, different from that found in subjects with chronic interstitial edema, suggesting that the pathophysiological characteristics of the two conditions may be different.     

Use of the isolated perfused rat lung in studies on lung lipid metabolism

A procedure for the use of the isolated perfused rat lung in studies on metabolic regulation has been developed. The procedure, reasonably uncomplicated, yet physiological, maintains the lung so that edema is not observed. The phospholipid content remains normal, and incorporation of [1-(14)C]-palmitate, [2-(14)C]acetate, and [U-(14)C]glucose is linear with time for a minimum of 2 hr. The incorporation of [1-(14)C]-palmitate and [2-(14)C]acetate into the total lung phospholipid fraction and into the phosphatidylcholine and phospatidylethanolamine fractions has been studied. Increasing the concentration of palmitate in the medium from 0.14 to 0.51 mm increased by 60% the incorporation of [1-(14)C]palmitate into the total lung phospholipid fraction at 2 hr. When the palmitate concentration of the medium was 0.14 mm, addition of 0.11 and 0.79 mm oleate to the medium decreased [1-(14)C]palmitate incorporation into the total lung phospholipid fraction at 2 hr by 37 and 49%, respectively. The results suggest that the incorporation of exogenous fatty acids, present in the medium perfusing the lung, into lung phospholipids may depend upon the fatty acid composition of the medium. Known specific acyltransferase activities may be responsible for the ordered incorporation of available fatty acids into lung phospholipids.     

Pulmonary circulation in experimental pulmonary edema during diverse artificial respiration regimes

In acute experiments on cats with closed chest by ultrasonic method the authors studied the blood flow in low-lobar pulmonary artery and the vein, the blood pressure in pulmonary artery, lung vessels resistance in experimental pulmonary edema caused by intravenous infusion of mixture fatty acids at artificial ventilation of increased frequencies or volumes, at was shown, that artificial ventilation of increased frequencies in pulmonary edema reduces the pressure increase in pulmonary artery, lung vessels resistance and increases the blood flow in pulmonary artery and vein. Artificial ventilation of increased volumes produces more intense pressure increase in pulmonary artery and lung vessels resistance than in initial ventilation but the blood flow was slightly changed. The authors assume that artificial ventilation of increased frequencies or volumes in pulmonary edema due to pulmonary circulation change reduces the pulmonary edema intensity at the beginning.     

Effects of cortisol on lipid and lipoprotein synthesis in rat hepatocytes]

Under in vivo conditions cortisol induces moderate hyperlipidemia followed by an increase in the phospholipid and triglyceride concentrations in the blood and a decrease of cholesterol; similar changes were observed in the liver. At all time intervals studied cortisol inhibits the phospholipid and cholesterol syntheses and decreases the specific radioactivities of the lipids in the mitochondrial fraction. The hormone has an inhibiting effect on the fatty acid synthesis at early postinjection stages. The phospholipid synthesis is increased after adrenalectomy and is then inhibited after injection of the hormone. A single injection of ACTH or cortisol causes suppression of phospholipid and cholesterol syntheses and a decrease in their specific radioactivities in the mitochondria. A similar effect is observed under stress conditions. In addition, the hormone inhibits the synthesis of lipoprotein apoproteins of very low and high densities. After 5 hours following the hormone injection the lipoprotein apoprotein synthesis in the liver is activated; the activation of apoprotein synthesis is also observed after adrenalectomy. However, the injection of the hormone to adrenalectomized rats decreases the apoprotein synthesis. It was shown that in blood serum cortisol affects the conversions of very low density lipoproteins into low density lipoproteins, thus providing for hyperlipidemia.     

Preliminary Investigation on the Effect of Dietary Supplemental Biotin and Palm Kernel Oil on Blood,Liver and Kidney Lipids in Chicks

Abstract

A total of 480 day-old broiler chicks were used in two trials conducted to investigate the performance and lipid contents of blood, liver and kidneys of birds when fed varying levels of palm kernel oil (0% and 2%) and biotin (40, 80, 120, 160, 200 and 240 mcg/kg feed) in a 2 × 6 factorial experimental design. The results showed that blood, liver and kidney lipid concentrations were significantly affected by dietary biotin treatments. While total lipid, free fatty acid, triglyceride and cholesterol contents were negatively correlated with dietary biotin level, phospholipid concentrations were positively correlated. Biotin-deficient chicks had significantly higher total lipid, free fatty acid, triglyceride and cholesterol but lower phospholipid contents in their blood and the two organs. Supplementation of the diet with 2% palm kernel oil significantly elevated blood phospholipid concentration, but depressed the accumulation of the other lipid fractions in both organs and the blood of birds. Blood, liver and kidney cholesterol concentrations were not affected by 2% fat supplementation. Observation on the lipid parameters coupled with the results on feed utilisation appeared to suggest that a minimum of 120 mcg of the vitamin per kilograme of diet was required by broiler chicks for optimum performance.     

The effect of N-stearoylethanolamine on lipid composition of the metastases and conditionally normal lung tissue in mice with Lewis carcinoma

Influence of NSE on lipid composition of metastases and the neighbouring conditionally normal lung tissue in mice with Lewis carcinoma was investigated. The processes of peroxidation in investigated tissues were also studied. It was shown that under the influence of NSE the high level of antioxidant activity in the metastases was decreased, while in the neighbouring conditionally normal lung tissue the catalase activity was increased. The content of the thiobarbituric acid-reactive substances in comparison with animals which were not fed by NSE was decreased. The development of carcinoma was accompanied by significant decrease of cholesterol level and by the increase of unsaturated fatty acids esterified in membrane phospholipids in both the metastases and the neighbouring conditionally normal lung tissue. An analysis of the phospholipid spectra shows that under tumor growth in investigated tissues the high-level lysophosphatidylcholine (LPC) was observed. The content of phosphatidyl choline (PC), phosphatidyl ethanolamine (PE), phosphatidyl serine (PS) was found to be significantly lower than in the lung of intact animals. It was found that administration of NSE to tumor-bearing mice contributed to the increase of cholesterol level, to the decrease of omega-6/omega-3 ratio polyunsaturated fatty acids of total phospholipids. NSE modulated the phospholipid membrane composition in both the metastases and the neighbouring conditionally normal lung tissue.     

The composition and function of the pulmonary surfactant system during metamorphosis in the tiger salamander Ambystoma tigrinum

Mammalian lungs secrete a mixture of surface-active lipids (surfactant), which greatly reduces the surface tension of the fluid coating the inner lung surface, thereby reducing the risk of collapse upon deflation and increasing compliance upon inflation. During foetal lung maturation, these lipids become enriched in the primary and active ingredient, a disaturated phopholipid. However, disaturated phospholipids exist in their inactive gellike form at temperatures below 37°C and thus are inappropriate for controlling surface tension in the lungs of many ectotherms. We examined the development of the composition and function of the surfactant system of the tiger salamander (Ambystoma tigrinum) during metamorphosis from the fully aquatic larva (termed stage I) through an intermediate air-breathing larval form (stage IV) to the terrestrial adult (stage VII). Biochemical analysis of lung washings from these three life stages revealed a decrease in the percentage of disaturated phospholipid per total phospholipid (23.03 versus 15.92%) with lung maturity. The relative cholesterol content remained constant. The increased level of phospholipid saturation in the fully aquatic larvae may reflect their generally higher body temperature and the higher external hydrostatic compression forces exerted on the lungs, compared to the terrestrial adults. Opening pressure (pressure required for initial lung opening) prior to lavage decreased from larval to adult salamanders (7.96 versus 4.69 cm H₂O), indicating a decrease in resistance to opening with lung development. Opening pressure increased after lavage in older aquatic (stage IV) larvae (5.36 versus 9.80 cm H₂O) and in the adults (4.69 versus 7.65 cm H₂O), indicating that the surfactant system in salamanders may have an antiglue function which prevents apposing epithelial surfaces from adhering together.Abbreviations bm body mass - Chol cholesterol - DSP disaturated phospholipid - PC phosphatidylcholine - PL phospholipid - postlav postlavage - prelav prelavage - P-V pressure-volume - RH relative humidity - T_b body temperature - USP unsaturated phospholipid - WL wet lung mass     

Carnosine prevents the activation of free-radical lipid oxidation during stress

Carnosine (beta-alanyl-L-histidine) injected to intact albino rats (20 mg/kg body weight) induces depletion of lipid peroxidation (LPO) products in brain and blood serum, an increase of superoxide scavenging activity in brain and serum, decrease of cholesterol: phospholipid ratio and increase of easy oxidizable phospholipid portion in brain lipid extracts. After painful stress (footshock during 2 hours) LPO products are accumulated in brain and serum, cholesterol: phospholipid ratio increases and the portion of easy oxidizable phospholipids decreases. Carnosine given before stress prevents LPO activation. Effects of carnosine and stress are not additive: LPO inhibition induced by carnosine is much more in rats subjected to stress.     

Plasma lecithin-cholesterol acyltransferase activity and cholesterol and phospholipid levels in premature newborn infants

Lecithin-cholesterol acyltransferase (LCAT) activity has been suggested to play an important role in the regulation of lipid metabolism. The present study was undertaken to examine any relationship between LCAT activity and altered cholesterol levels in plasma of full-term and preterm newborn infants. Plasma total, free and esterified cholesterol, total phospholipid and LCAT activity (cholesterol esterified, nmol/ml per h) were determined in placental cord blood. There was a significant negative relationship between total cholesterol levels and gestational age. The increased cholesterol with prematurity was due to both free and esterified cholesterol. There was also a significant negative relationship between LCAT activity and free cholesterol levels but not between LCAT activity and total cholesterol and esterified cholesterol levels. There was no relationship between esterified-to-free cholesterol ratio and LCAT activity. Total phospholipid was not significantly related to either gestational age or LCAT activity. This study suggests that reduced LCAT activity may be one of the factors that result in the accumulation of cholesterol in premature infants.     

Effect of simvastatin on the uptake and metabolic conversion of palmitic, dihomo-gamma-linoleic and alpha-linolenic acids in A549 cells

It is well known that simvastatin affects cholesterol synthesis. Furthermore it inhibits growth and proliferation and perturbs fatty acid metabolism in some cell lines. We have studied the effects of simvastatin on the uptake and metabolism of exogenous fatty acid in the human lung adenocarcinoma A549 cells. Simvastatin inhibited the proliferation of A549, and caused an increment in phospholipid/cholesterol ratio due to an increment in phospholipid content without affecting cholesterol content. All the fatty acids were uptaken and metabolized in both control and treated cells. The conversion of palmitic, linoleic and dihomo-gamma-linoleic acids to their metabolites and products/precursor ratios for the desaturation and elongation reactions showed that simvastatin enhanced the Delta5 desaturation step and altered some elongating steps. The machinery for unsaturated fatty acid synthesis in A549 is quite sensitive to simvastatin and its effects could have important implication taking into account that highly unsaturated fatty acids are involved in the regulation of diverse cellular functions by themselves or through their metabolites.     

Robust passive and active efflux of cellular cholesterol to a designer functional mimic of high density lipoprotein

The ability of HDL to support macrophage cholesterol efflux is an integral part of its atheroprotective action. Augmenting this ability, especially when HDL cholesterol efflux capacity from macrophages is poor, represents a promising therapeutic strategy. One approach to enhancing macrophage cholesterol efflux is infusing blood with HDL mimics. Previously, we reported the synthesis of a functional mimic of HDL (fmHDL) that consists of a gold nanoparticle template, a phospholipid bilayer, and apo A-I. In this work, we characterize the ability of fmHDL to support the well-established pathways of cellular cholesterol efflux from model cell lines and primary macrophages. fmHDL received cell cholesterol by unmediated (aqueous) and ABCG1- and scavenger receptor class B type I (SR-BI)-mediated diffusion. Furthermore, the fmHDL holoparticle accepted cholesterol and phospholipid by the ABCA1 pathway. These results demonstrate that fmHDL supports all the cholesterol efflux pathways available to native HDL and thus, represents a promising infusible therapeutic for enhancing macrophage cholesterol efflux. fmHDL accepts cholesterol from cells by all known pathways of cholesterol efflux: unmediated, ABCG1- and SR-BI-mediated diffusion, and through ABCA1.     

Hypoxia enhances unilateral lung injury by increasing blood flow to the injured lung

We hypothesized that in unilateral lung injury, bilateral hypoxic ventilation would induce vasoconstriction in the normal lung, redirect blood flow to the injured lung, and cause enhanced edema formation. Unilateral left lung injury was induced by intrabronchial instillation of 1.5 ml/kg of 0.1 N HCl. After HCl injury, blood flow to the injured left lung decreased progressively from 0.70 +/- 0.04 to 0.37 +/- 0.05 l/min and percent of flow to the injured left lung (QL/QT) decreased from 37.7 +/- 2.2 to 23.6 +/- 2.2% at 240 min. Exposure to hypoxia (12% O2) for three 10-min episodes did not affect QL/QT in normal animals, but after unilateral HCl injury, it caused blood flow to the injured left lung to increase significantly. A concomitant decrease in blood flow occurred to the noninjured right lung, resulting in a significant increase in QL/QT. The enhanced blood flow to the injured lung was associated with a significant increase in the wet-to-dry lung weight ratio in the dependent regions of the injured lung. These findings demonstrate that in unilateral HCl-induced lung injury, transient hypoxia can enhance blood flow to the areas of injury and increase lung edema formation.     

The effect of changes in the lipid composition of membranes on the functional activity of platelets

The phospholipid and fatty acid composition as well as the effect of platelet lipid composition modifications on the functional parameters of platelets were studied in blood sera from healthy donors and from patients with ischemic heart disease (IHD). It was found that the content of cholesterol and phospholipid hydrolysis products in IHD patients was increased. Reconstitution of the lipid composition of donor platelets by lysophosphatidylcholines, phosphatidic acid, fatty acids and cholesterol led to the increase of the platelet functional activity. It is suggested that the increased adsorption of Ca2+ on platelet surface is due to alterations in the platelet lipid composition in IHD and after modifications.     

Effect of qualitatively different carbohydrates on the lipoprotein spectrum and lipid composition of the blood in experimental animals]

Experiments on rats demonstrated that a high-carbohydrate diet with starch produced no changes in the lipoprotein composition and lipid concentration in the blood. Diets containing sucrose promoted an increase in triglycerides and of the pre-beta-lipoproteins. However, the effect of sucrose depended on the qualitative correlation of the carbohydrate and lipid components of the diet. A reduction of lipoproteins of low density and of the total cholesterol/phospholipid ratio on account of an increase of the latter in the blood was seen in rats given sucrose in the composition of the high-carbohydrate diet with a decreased amount of the saturated fat. Inclusion of sucrose into the diet with a physiological carbohydrate and lipid level (56 and 26% of total amount of calories, respectively) was accompanied by elevation of beta-lipoprotein level and an increase in the total cholesterol/phospholipid ratio.     

Incorporation of cholesterol into serum high density lipoprotein apoprotein and recombinants

The uptake of cholesterol (CHL) by serum high density lipoprotein (HDL) delipidated apoproteins and phospholipid-apoprotein recombinants has been studied with two methods; by incubation with Celite-dispersed cholesterol or with cholesterol crystals. The apoproteins bind very small amounts of cholesterol with a maximum of about 6 micrograms/mg apoprotein. Recombinants with dimyristoyl phosphatidylcholine (DMPC) or egg phosphatidylcholine (EPC) as phospholipid component gave similar values for cholesterol uptake. The initial rate for uptake from Celite-cholesterol by recombinants was high (0.1 mol cholesterol/mol phospholipid/h) and somewhat higher than that for phospholipid vesicles. The maximal uptake was by gel filtration shown to depend on the size of the complexes with values about 0.95 mol cholesterol per phospholipid for vesicular complexes, 0.75 for discoidal complexes and between 0.5 and 0.2 for small 'protein-rich' complexes. During the incubation of recombinants with cholesterol there was considerable decomposition of discoidal complexes and formation of larger ones. The results show that phospholipid-apoprotein complexes are efficient acceptors for cholesterol but also that about 25% of the phospholipid in the discoidal complexes is excluded from interaction with cholesterol by interaction with apoprotein.