Mitigation of Surfactant Erythrocyte Toxicity by Egg Phosphatidylcholine (original) (raw)
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Chemico-biological Interactions, 1998
The effects of three different poly[oxyethylene (n) nonylphenols], n= 9.5, 20 and 100 oxyethylene (EO) units, on erythrocyte hemolysis and on the fluidity of the erythrocyte membrane were studied. The three different surfactants showed different effects. The surfactant with average n=9.5 EO units (C9E9) shows a biphasic effect: at low concentrations it protects erythrocytes against hypotonic hemolysis, but at higher concentrations it induces hemolysis both in isotonic and hypotonic buffers. C9E20 does not affect the erythrocyte membrane resistance to hemolysis, independent of the buffer osmolarity; this detergent did not show a hemolytic effect. C9E100 is an effective protective agent against hypotonic hemolysis, in concentrations \2×10 − 4 M. EPR spectroscopy of spin-labeled stearic acid indicated that the three different surfactants increase the fluidity of erythrocyte ghost membranes. At the higher C9E20 and C9E100 surfactant concentrations in the presence of membrane ghosts, spin-label is located in the surfactant micelles. In the case of the hemolytic concentrations of C9E9, mixed (surfactant plus phospholipid) micelles are formed. These results suggest that C9E9 has a higher affinity for membrane phospholipids, which accounts for its lytic activity. The protective effect of C9E100 is assigned to the osmotic buffering of the liquid surrounding the cell membrane, due to the large polar chains anchored to the membrane outer monolayer but other mechanisms previously considered in the literature may also be effective.
Haemolytic Action of Non‐ionic Surfactants Derived from Lysine in Rat Erythrocytes
Monodisperse, non-ionic surfactants based on lysine contain two hydrophobic chains and one or two polyoxyethylene glycol chains with a methoxy group capping the terminal hydroxyl function. Because their structural resemblance to lecithins suggests they could be regarded as non-ionic molecular mimics of these compounds, their haemolytic action has been studied.The presence of 14 and 18 carbon atoms in the hydrophobic moiety seems to result in greater haemolytic action of the surfactants with one polyoxyethylene glycol chain. In the series with two polyoxyethylene glycol chains, the compounds tested at a concentration higher than their critical micellar concentration have greater haemolytic effect, irrespective of the shape of the micelles. When there is a single polyoxyethylene chain a relationship is observed between chain length and haemolytic effect. This correlation is not observed for compounds with two chains.The results show that it is not always possible to predict the haemol...
The aim of this study is to evaluate the effect of polyethylene glycol brij ethers surfactants group on red blood cells as a model for biological membranes. Also in this study, physicochemical properties including emulsification index (E 24), foam producing activity (F h) and critical micelle concentration (cmc) were studied. Surfactant solutions were prepared in McIvan's buffer in specific concentrations. 0.2 ml of red blood cells (RBC) was mixed with 0.2 ml of each surfactant solution. The four surfactant solutions had each been incubated differently at two different temperatures for three different times. Each test was done six times. The results were presented as mean absorbance ± the standard deviation. E 24 , F h and cmc were also determined for each surfactant solution. All of the surfactant solutions showed hemolytic activity. In comparison with the four studied surfactants, brij 56 had the highest hemolytic effect and brij 72 the lowest. The values of E 24 and F h had good correlation with hydrophilic-lipophilic balance values. According to the results of this study, brijs should be used at concentrations lower than cmc in formulations. Also, according to the results, the use of brijs with low hemolytic effect such as brij 72, is preferred in pharmaceutical preparations.
Surfactant-induced cell toxicity and cell lysis
Biochemical Pharmacology, 1990
The effects of a variety of detergents (non-ionic, ionic and bile derivatives) on B16 melanoma cells have been examined. Two main effects can be clearly differentiated: loss of cell viability and cell lysis. Under our conditions, cell-surfactant interaction is highly dependent on the nature of the amphiphile (more specifically, on its critical micellar concentration). Loss of cell viability occurs at surfactant concentrations below the critical micellar concentration, i.e. the incorporation of detergent monomers into the cell membranes is enough to impair their barrier function, so that Trypan Blue is no longer actively secreted outside the cell. On the other hand, cell lysis only occurs at or near the critical micellar concentration of the detergent, i.e. when the bilayer-micelle transition may take place. Comparative studies using B16 cells and phospholipid vesicles indicate that the amount of detergent required to induce cell lysis is the same that produces disruption of the lipid bilayer. Thus, our results suggest that membranes are the primary target for the toxicologic effects of surfactants on cells. Moreover, they provide a rationale for the interpretation of other studies in this field: previous results from different laboratories are shown to fit very well our data.
Differential effect of surfactant and its saturated phosphatidylcholines on human blood macrophages
Journal of Lipid Research, 2006
Blood monocyte-derived macrophages invading the alveolus encounter pulmonary surfactant, a phospholipoprotein complex that changes composition during lung development. We tested the hypothesis that characteristic phosphatidylcholine (PC) components differentially influence macrophage phenotype and function, as determined by phagocytosis of green fluorescent protein-labeled Escherichia coli and aCD3-induced T cell proliferation. Human macrophages were exposed to surfactant (Curosurf:), to two of its characteristic phosphadidylcholine (PC) components (dipalmitoyl-PC and palmitoylmyristoyl-PC), and to a ubiquituous PC (palmitoyloleoyl-PC) as control. Interaction of Curosurf and PC species with macrophages was assessed using Lissaminei-dihexadecanoyl-phosphoethanolaminelabeled liposomes. Curosurf and both saturated surfactant PC species downregulated CD14 expression and upregulated CD206. HLA-DR and CD80 were upregulated by Curosurf and palmitoylmyristoyl-PC, whereas dipalmitoyl-PC showed no effect. The latter upregulated TLR2 and TLR4 expression, whereas Curosurf and palmitoylmyristoyl-PC had no effect. PC species tested were incorporated in comparable amounts by macrophages. Curosurf and PC species inhibited phagocytosis of E. coli. Scavenger receptor CD36, CD68, SR-A, and LOX-1 mRNA expression was upregulated by Curosurf, whereas PC species only upregulated SR-A. Curosurf and palmitoylmyristoyl-PC inhibited aCD3induced T cell proliferation by 50%, whereas dipalmitoyl-PC and palmitoyloleoyl-PC showed no effect. These data identify individual surfactant PC species as modifiers of macrophage differentiation and suggest differential effects on innate and adaptive immune functions.
A comparative study of mechanisms of surfactant inhibition
Biochimica et Biophysica Acta (BBA) - Biomembranes, 2008
Pulmonary surfactant spreads to the hydrated air-lung interface and reduces the surface tension to a very small value. This function fails in acute respiratory distress syndrome (ARDS) and the surface tension stays high. Dysfunction has been attributed to competition for the air-lung interface between plasma proteins and surfactant or, alternatively, to ARDS-specific alterations of the molecular profile of surfactant. Here, we compared the two mechanisms in vitro, to assess their potential role in causing respiratory distress. Albumin and fibrinogen exposure at or above blood level concentrations served as the models for testing competitive adsorption. An elevated level of cholesterol was chosen as a known adverse change in the molecular profile of surfactant in ARDS. Bovine lipid extract surfactant (BLES) was spread from a small bolus of a concentrated suspension (27 mg/ml) to the air-water interface in a captive bubble surfactometer (CBS) and the bubble volume was cyclically reduced and increased to assess surface activity of the spread material. Concentrations of inhibitors and the concentration and spreading method of pulmonary surfactant were chosen in an attempt to reproduce the exposure of surfactant to inhibitors in the lung. Under these conditions, neither serum albumin nor fibrinogen was persistently inhibitory and normal near-zero minimum surface tension values were obtained after a small number of cycles. In contrast, inhibition by an increased level of cholesterol persisted even after extensive cycling. These results suggest that in ARDS, competitive adsorption may not sufficiently explain high surface tension, and that disruption of the surfactant film needs to be given causal consideration.
Hemolysis and antihemolysis induced by amino acid-based surfactants
Toxicology Letters, 2007
Surfactants have the special ability to interact with the lipid bilayer of cell membranes. The red blood cell is one of the most used cellular membrane models to study the mechanisms underlying surfactant-induced osmotic cell resistance. To increase our knowledge regarding the mechanisms of surfactant membrane interaction, we studied the action of five lysine-derivative anionic and three arginine-derivative cationic amino acid-based surfactants on hypotonic hemolysis. Results showed two different antihemolytic behaviors among amino acid-based surfactants, both related to the maximal protective concentration. How the physico-chemical properties and structure of these compounds determine the protection against hypotonic hemolysis is discussed in detail. We found a good correlation between the CMC and the concentrations resulting in maximum protection against hypotonic hemolysis for the cationic surfactants, but no correlation for the anionic surfactants. In the case of lysine derivative surfactants, which only differ in their counterions, the counterion is implicated in the differences in the antihemolytic potency and the hemolytic activities of this.
Pediatric Research, 1988
C were isolated from lavage fluids of bovine lungs and recombined (lipid/proteins, 911, wt/wt) with dipalmitoyl phosphatidylcholine for testing in vitro and in surfactantdeficient adult rats. Using a pulsating bubble surfactometer, we found that inflation pressures of bubbles at minimum radii in these mixtures were 0.34 f 0.05 cm H 2 0 (+ SD, n = 24) after 1 min. These values were not affected by increasing amounts of surfactant protein relative to dipalmitoyl phosphatidylcholine (DPPC). Minimum inflation pressures were similar to those of modified bovine surfactant, surfactant Tokyo Akita (TA) (0.33 f 0.05 cm H20, n = 7). I n vivo testing was carried out in adult rats made surfactant deficient by repeated lavage and ventilated with 100% oxygen. Rats received tracheal instillations of either air, DPPC, DPPCISP-B,C (9:1), or surfactant TA at 50 mg/kg body weight. Surfactant TA and DPPCISP-B, SP-C mixtures resulted in similar immediate and sustained improvements in arterial oxygenation (308 + 66 torr, n = 10 and 312 2 101 torr, n = 6 at 30 min posttreatment) that were significantly greater than those of sham (76 f 24 torr, n = 17) and DPPC-treated rats (64 f 32 torr, n = 7). Rats treated with either DPPC/SP-B,C mixtures or surfactant TA showed similar postmortem static lung compliances (2.3 f 0.8 ml/cm H20/kg, n = 8 and 1.9 2 0.4 ml/cm H20/kg, n = 5, respectively) that were significantly larger than sham (1.3 + 0.3 ml/cm H 2 0 / kg, n = 14) and DPPC-treated rats (1.2 f 0.2 ml/cm H20/ kg, n = 6). We conclude that simple mixtures of DPPC and SP-B,C duplicate results found with more complex mixtures of pulmonary surfactants.
Interactions of Novel, Nonhemolytic Surfactants with Phospholipid Vesicles
Langmuir, 2007
PEG-12-acyloxystearates constitute a novel class of pharmaceutical solubilizers and are synthesized from polyethylene glycol and 12-hydroxystearic acid, which has been esterified with a second acyl chain. The hemolytic activity of these surfactants decreases drastically with increasing pendant acyloxy chain length, and surfactants with an acyloxy chain of 14 carbon atoms or more are essentially nonhemolytic. In this paper, the interactions of PEG-12-acyloxystearates (acyloxy chain lengths ranging from 8 to 16 carbon atoms) with phosphatidylcholine vesicles, used as a model system for erythrocyte membranes, were studied in search of an explanation for the large variations in hemolytic activity. Surfactant-induced alterations of membrane permeability were investigated by studying the leakage of vesicle-entrapped calcein. It was found that all of the surfactants within the series interact with the vesicle membranes and cause slow leakage at elevated surfactant concentrations, but with large variations in leakage kinetics. The initial leakage rate decreases rapidly with increasing pendant acyloxy chain length. After prolonged incubation, on the other hand, the leakage is not a simple function of acyloxy chain length. The effect of the surfactants on membrane integrity was also investigated by turbidity measurements and cryo-transmission electron microscopy. At a surfactant/lipid molar ratio of 0.4, the vesicle membranes are saturated with surfactant. When the surfactant/lipid molar ratio is further increased, the vesicle membranes are progressively solubilized into mixed micelles. The rate of this process decreases strongly with increasing acyloxy chain length. When comparing the results of the different experiments, it can be concluded that there is no membrane permeabilization below saturation of the vesicle membranes. The large variations in the kinetics suggest that several steps are involved in the mechanism of leakage induced by PEG-12-acyloxystearates and that their relative rates vary with acyloxy chain length. The slow kinetics may in part be explained by the low critical micelle concentrations (CMCs) exhibited by the surfactants. The CMCs were found to be in the range of 0.003-0.025 µM.
Gemini (dimeric) surfactant perturbation of the human erythrocyte
Acta biochimica Polonica, 2000
We studied the ability of di-cationic gemini surfactantsdi (amphiphiles), i.e. 1,4-butanediammonium-N,N-dialkyl-N,N,N',N'-tetramethyl bromides (Di-Cm-di-QAS (s = 4), where m = 8, 11, 13, 16 and s = the number of alkyl groups in the spacer) to induce shape alteration, vesiculation, haemolysis and phosphatidylserine exposure in human erythrocytes, and to protect erythrocytes against hypotonic haemolysis. At high sublytic concentrations the Di-Cm-di-QAS (s = 4) amphiphiles rapidly induced echinocytic (spiculated) shapes and a release of exovesicles, mainly in the form of tubes, from the cell surface. Following 60 min incubation erythrocytes were sphero-echinocytic and a few cells with invaginations/endovesicles were observed. No phosphatidylserine exposure was detected. The haemolytic potency increased with an increase of the alkyl chain length. At sublytic concentrations the Di-Cm-di-QAS (s = 4) amphiphiles protected erythrocytes against hypotonic haemolysis. It is suggested t...