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Proceedings of the National Academy of... Mar 1972A hydrogen-bonding interaction between phenobarbital or pentobarbital with phosphatidylcholine in chloroform is indicated by the effects of added phosphatidylcholine on...
A hydrogen-bonding interaction between phenobarbital or pentobarbital with phosphatidylcholine in chloroform is indicated by the effects of added phosphatidylcholine on the infrared and proton magnetic resonance spectra of these barbiturates. The nitrogenbound proton of the barbiturate and the orthophosphate moiety of the phosphatidylcholine molecule appear to be involved. The more pronounced effect with the two barbiturates occurs in the proton magnetic resonance spectra of phenobarbital with increased amounts of phosphatidylcholine. A plot of the chemical shift of phenobarbital N-H against the concentration of phosphatidylcholine is linear and gives an extrapolated shift of 260 Hz (2.6 ppm) at 35 degrees C for a phosphatidylcholine-phenobarbital ratio of unity, pure 1:1 complex. It is suggested that the general depressant nature of barbiturates may be accounted for by their association in a similar fashion with a number of other phosphate-containing molecules.
Topics: Chemical Phenomena; Chemistry; Magnetic Resonance Spectroscopy; Pentobarbital; Phenobarbital; Phosphatidylcholines
PubMed: 4501578
DOI: 10.1073/pnas.69.3.640 -
Journal of Oleo Science Nov 2017Structured phosphatidylcholine was successfully produced by acidolysis between phosphatidylcholine and free medium chain fatty acid, using phospholipase A immobilized on...
Structured phosphatidylcholine was successfully produced by acidolysis between phosphatidylcholine and free medium chain fatty acid, using phospholipase A immobilized on Duolite A568. Response surface methodology was applied to optimize the reaction system using three process parameters: molar ratio of substrates (phosphatidylcholine to free medium chain fatty acid), enzyme loading, and reaction temperature. All parameters evaluated showed linear and quadratic significant effects on the production of modified phosphatidylcholine; molar ratio of substrates contributed positively, but temperature influenced negatively. Increased enzyme loading also led to increased production of modified phosphatidylcholine but only during the first 9 hours of the acidolysis reaction. Optimal conditions obtained from the model were a ratio of phosphatidylcholine to free medium chain fatty acid of 1:15, an enzyme loading of 12%, and a temperature of 45°C. Under these conditions a production of modified phosphatidylcholine of 52.98 % were obtained after 24 h of reaction. The prediction was confirmed from the verification experiments; the production of modified phosphatidylcholine was 53.02%, the total yield of phosphatidylcholine 64.28% and the molar incorporation of medium chain fatty acid was 42.31%. The acidolysis reaction was scaled-up in a batch reactor with a similar production of modified phosphatidylcholine, total yield of phosphatidylcholine and molar incorporation of medium chain fatty acid. Purification by column chromatography of the structured phosphatidylcholine yielded 62.53% of phosphatidylcholine enriched with 42.52% of medium chain fatty acid.
Topics: Chemistry Techniques, Synthetic; Esterification; Fatty Acids; Hydrolysis; Kinetics; Models, Chemical; Molecular Structure; Phosphatidylcholines; Phospholipases A1; Temperature
PubMed: 29021492
DOI: 10.5650/jos.ess17087 -
Journal of Oleo Science Jul 2016Recent studies have shown that EPA enriched PLs have beneficial effects on lipid metabolism. Our previous study has demonstrated that the anti-obesity and hypolipidemic... (Comparative Study)
Comparative Study
Recent studies have shown that EPA enriched PLs have beneficial effects on lipid metabolism. Our previous study has demonstrated that the anti-obesity and hypolipidemic effects of EPA-PL were superior to DHA-PL. In the present study, we comparatively evaluated the effects of EPA-enriched phosphatidylcholine (EPA-PC) and EPA-enriched phosphatidylserine (EPA-PS) on lipid metabolism in mice. Both 2% dietary EPA-PC and EPA-PS significantly improved serum and hepatic lipid levels in mice. The HDL-c level in mice on EPA-PC diet was significantly higher than the other two groups. The level of DHA in hepatic TG and PL were significantly increased in both EPA-PC and EPA-PS fed groups (98.3 and 117.8%, respectively; p < 0.05). Notably, the proportion of DHA in EPA-PS group was significantly higher than the EPA-PC group. EPA-PC and EPA-PS suppressed hepatic SREBP-1c mediated lipogenesis and activated PPARα mediated fatty acid β-oxidation in the liver. These data are the first to indicate that EPA-PS has beneficial effects on lipid metabolism.
Topics: Animals; Eicosapentaenoic Acid; Lipid Metabolism; Lipids; Male; Mice; Mice, Inbred Strains; Phosphatidylcholines; Phosphatidylserines
PubMed: 27321119
DOI: 10.5650/jos.ess16005 -
Langmuir : the ACS Journal of Surfaces... Nov 2019This study provides insights into dynamic nanostructural changes in phospholipid systems during hydrolysis with phospholipase C, the fate of the hydrolysis products, and...
This study provides insights into dynamic nanostructural changes in phospholipid systems during hydrolysis with phospholipase C, the fate of the hydrolysis products, and the kinetics of lipolysis. The effect of lipid restructuring of the vesicle was investigated using small-angle X-ray scattering and cryogenic scanning electron microscopy. The rate and extent of phospholipid hydrolysis were quantified using nuclear magnetic resonance. Hydrolysis of two phospholipids, phosphatidylethanolamine (PE) and phosphatidylcholine (PC), results in the cleavage of the molecular headgroup, causing two strikingly different changes in lipid self-assembly. The diacylglycerol product of PC escapes the lipid bilayer, whereas the diacylglycerol product adopts a different configuration within the lipid bilayer of the PE vesicles. These results are then discussed concerning the change of the lipid configuration upon the lipid membrane and its potential implications in vivo, which is of significant importance for the detailed understanding of the fate of lipidic particles and the rational design of enzyme-responsive lipid-based drug delivery systems.
Topics: Drug Delivery Systems; Drug Liberation; Hydrolysis; Lipid Bilayers; Magnetic Resonance Spectroscopy; Membrane Lipids; Micelles; Microscopy, Electron, Scanning; Phosphatidylcholines; Phosphatidylethanolamines; Phospholipids; Scattering, Small Angle; Type C Phospholipases; X-Ray Diffraction
PubMed: 31642682
DOI: 10.1021/acs.langmuir.9b02288 -
Medical Science Monitor : International... Dec 2017BACKGROUND The aim of this study was to evaluate the efficacy and safety of bicyclol treatment in statin-induced liver injury. MATERIAL AND METHODS The study included... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND The aim of this study was to evaluate the efficacy and safety of bicyclol treatment in statin-induced liver injury. MATERIAL AND METHODS The study included 168 patients with liver injury caused by statins. Patients were randomized into two four-week treatment groups: bicyclol 25 mg three times daily or polyene phosphatidylcholine 456 mg three times daily as control. Serum biochemical indexes were compared before and after treatment. RESULTS Significant differences in alanine transaminase (ALT) levels among the three measurements before and after treatment in the two groups at different time points were observed (p<0.01). There was a significant difference (p<0.01) between two weeks and four weeks after treatment compared to the baseline period. There was a significant interaction (p=0.003) between the two groups and time factors. After two and four weeks of treatment, the ALT levels in the control group (68.20±26.31, 50.71±27.13 respectively) were higher compared to the ALT in the bicyclol group (49.33±21.39, 30.36±17.41 respectively) (p<0.01). After four weeks of treatment, the normalization rates of bicyclol and polyene phosphatidylcholine groups were 74.68% and 46.15%, respectively. The efficacy of bicyclol was significantly better than that of polyene phosphatidylcholine (p<0.05). The incidence of adverse reactions in the bicyclol and polyene phosphatidylcholine groups were 2.53% and 2.56%, respectively, with no statistically significant differences observed between the two groups (p>0.05). CONCLUSIONS These findings suggest that trends of ALT changes in the two groups were different, and the improvement of ALT was more obvious in the bicyclol group. Bicyclol is considered to be safe and effective in the treatment of statin-induced liver injury.
Topics: Adult; Aged; Alanine Transaminase; Biphenyl Compounds; Chemical and Drug Induced Liver Injury; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Liver; Male; Middle Aged; Phosphatidylcholines
PubMed: 29200411
DOI: 10.12659/msm.904090 -
Scientific Reports Nov 2020Topical ophthalmic antibiotics show low efficacy due to the well-known physiological defense mechanisms of the eye, which prevents the penetration of exogenous...
Topical ophthalmic antibiotics show low efficacy due to the well-known physiological defense mechanisms of the eye, which prevents the penetration of exogenous substances. Here, we aimed to incorporate besifloxacin into liposomes containing amines as positively charged additives and to evaluate the influence of this charge on drug delivery in two situations: (i) iontophoretic and (ii) passive treatments. Hypothesis are (i) charge might enhance the electromigration component upon current application improving penetration efficiency for a burst drug delivery, and (ii) positive charge might prolong formulation residence time, hence drug penetration. Liposomes elaborated with phosphatidylcholine (LP PC) or phosphatidylcholine and spermine (LP PC: SPM) were stable under storage at 6 ºC for 30 days, showed mucoadhesive characteristics, and were non-irritant, according to HET-CAM tests. Electron paramagnetic resonance spectroscopy measurements showed that neither the drug nor spermine incorporations produced evident alterations in the fluidity of the liposome's membranes, which retained their structural stability even under iontophoretic conditions. Mean diameter and zeta potential were 177.2 ± 2.7 nm and - 5.7 ± 0.3 mV, respectively, for LP PC; and 175.4 ± 1.9 nm and + 19.5 ± 1.0 mV, respectively, for LP PC:SPM. The minimal inhibitory concentration (MIC) and the minimal bactericide concentration (MBC) of the liposomes for P. aeruginosa showed values lower than the commercial formulation (Besivance). Nevertheless, both formulations presented a similar increase in permeability upon the electric current application. Hence, liposome charge incorporation did not prove to be additionally advantageous for iontophoretic therapy. Passive drug penetration was evaluated through a novel in vitro ocular model that simulates the lacrimal flow and challenges the formulation resistance in the passive delivery situation. As expected, LP PC: SPM showed higher permeation than the control (Besivance). In conclusion, besifloxacin incorporation into positively charged liposomes improved passive topical delivery and can be a good strategy to improve topical ophthalmic treatments.
Topics: Administration, Ophthalmic; Animals; Azepines; Eye; Fluoroquinolones; Liposomes; Permeability; Phosphatidylcholines; Swine
PubMed: 33159142
DOI: 10.1038/s41598-020-76381-y -
Journal of Lipid Research Dec 2017Cholesterol, an essential component in biological membranes, is highly unevenly distributed within the cell, with most localized in the plasma membrane while only a...
Cholesterol, an essential component in biological membranes, is highly unevenly distributed within the cell, with most localized in the plasma membrane while only a small fraction is found in the endoplasmic reticulum, where it is synthesized. Cellular membranes differ in lipid composition and protein content, and these differences can exist across their leaflets too. This thermodynamic landscape that cellular membranes impose on cholesterol is expected to modulate its transport. To uncover the role the membrane environment has on cholesterol inter- and intra-membrane movement, we used time-resolved small angle neutron scattering to study the passive movement of cholesterol between and within membranes with varying degrees of saturation content. We found that cholesterol moves systematically slower as the degree of saturation in the membranes increases, from a palmitoyl oleyl phosphotidylcholine membrane, which is unsaturated, to a dipalmitoylphosphatidylcholine (DPPC) membrane, which is fully saturated. Additionally, we found that the energetic barrier to move cholesterol in these phosphatidylcholine membranes is independent of their relative lipid composition and remains constant for both flip-flop and exchange at ∼100 kJ/mol. Further, by replacing DPPC with the saturated lipid palmitoylsphingomyelin, an abundant saturated lipid of the outer leaflet of the plasma membrane, we found the rates decreased by a factor of two. This finding is in stark contrast with recent molecular dynamic simulations that predict a dramatic slow-down of seven orders of magnitude for cholesterol flipping in membranes with a similar phosphocholine and SM lipid composition.
Topics: 1,2-Dipalmitoylphosphatidylcholine; Biological Transport; Cholesterol; Kinetics; Phosphatidylcholines; Sphingomyelins; Thermodynamics; Unilamellar Liposomes
PubMed: 29046341
DOI: 10.1194/jlr.M077909 -
Chemistry and Physics of Lipids Apr 2017The phospholipid (PL) composition of embryo and oocyte membranes affects thermal phase behavior and several physicochemical properties such as fluidity and permeability....
The phospholipid (PL) composition of embryo and oocyte membranes affects thermal phase behavior and several physicochemical properties such as fluidity and permeability. The characterization of PL profiles and the development of suitable in vitro maturation (IVM) protocols, that are able to modify membrane's composition, may result in significant improvements in oocyte developmental potential and cryotolerance. Using soybean phosphatidylcholine (PC) as a model supplement, we evaluated the effect of PL supplementation during IVM on bovine cumulus-oocyte-complex (COC). Substantial changes in the lipid profiles of oocyte membrane were observed and associated with pre-implantation data. The propensity of the PC supplement to become soluble in the maturation medium and/or diffuse into mineral oil was also assessed. Oocytes were matured in TCM without supplementation, i.e. control, (n=922) or supplemented with 50 or 100μM PC (n=994). The maturation media and mineral oil pre- and post- IVM, along with control and PC-treated oocytes were then analyzed using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), and the lipid profiles were compared via principal component analysis (PCA). Soybean PCs are bioavailable and stable in IVM medium; further, PCs did not diffuse to the mineral oil, which also remained unaltered by the metabolism of treated oocytes. PC supplementation at 100μM resulted in substantially greater relative abundances of polyunsatured PL, namely PC (32:1), PC (34:2), PC (36:6), PC (36:4), and PC (38:6), in oocyte membrane. These differences indicated that short-term exposure to the PC supplement could indeed modify the lipid composition of IVM-oocytes in a dose-dependent manner. Membrane incorporation of polyunsaturated molecular species of PC was favored, and does so without compromising the viability of the subsequent embryo in regards to cleavage, blastocyst development and hatching rate. The reported approach will allow for the development of novel strategies to modulate oocyte membrane dynamics and structure.
Topics: Animals; Cattle; Cell Membrane; Dose-Response Relationship, Drug; In Vitro Techniques; Lipids; Oocytes; Phosphatidylcholines; Principal Component Analysis; Glycine max; Structure-Activity Relationship
PubMed: 28336451
DOI: 10.1016/j.chemphyslip.2017.03.003 -
The Journal of Clinical Investigation Nov 2017Liver triacylglycerol (TAG) synthesis and secretion are closely linked to nutrient availability. After a meal, hepatic TAG formation from fatty acids is decreased,...
Liver triacylglycerol (TAG) synthesis and secretion are closely linked to nutrient availability. After a meal, hepatic TAG formation from fatty acids is decreased, largely due to a reduction in circulating free fatty acids (FFA). Despite the postprandial decrease in FFA-driven esterification and oxidation, VLDL-TAG secretion is maintained to support peripheral lipid delivery and metabolism. The regulatory mechanisms underlying the postprandial control of VLDL-TAG secretion remain unclear. Here, we demonstrated that the mTOR complex 1 (mTORC1) is essential for this sustained VLDL-TAG secretion and lipid homeostasis. In murine models, the absence of hepatic mTORC1 reduced circulating TAG, despite hepatosteatosis, while activation of mTORC1 depleted liver TAG stores. Additionally, mTORC1 promoted TAG secretion by regulating phosphocholine cytidylyltransferase α (CCTα), the rate-limiting enzyme involved in the synthesis of phosphatidylcholine (PC). Increasing PC synthesis in mice lacking mTORC1 rescued hepatosteatosis and restored TAG secretion. These data identify mTORC1 as a major regulator of phospholipid biosynthesis and subsequent VLDL-TAG secretion, leading to increased postprandial TAG secretion.
Topics: Animals; Cells, Cultured; Fatty Liver; Hepatocytes; Lipogenesis; Liver; Male; Mechanistic Target of Rapamycin Complex 1; Mice, Inbred C57BL; Mice, Transgenic; Phosphatidylcholines; Triglycerides
PubMed: 29035283
DOI: 10.1172/JCI96036 -
Biochimica Et Biophysica Acta Oct 2016Accurate details on the sampled atomistic resolution structures of lipid bilayers can be experimentally obtained by measuring C-H bond order parameters, spin relaxation... (Review)
Review
Accurate details on the sampled atomistic resolution structures of lipid bilayers can be experimentally obtained by measuring C-H bond order parameters, spin relaxation rates and scattering form factors. These parameters can be also directly calculated from the classical atomistic resolution molecular dynamics simulations (MD) and compared to the experimentally achieved results. This comparison measures the simulation model quality with respect to 'reality'. If agreement is sufficient, the simulation model gives an atomistic structural interpretation of the acquired experimental data. Significant advance of MD models is made by jointly interpreting different experiments using the same structural model. Here we focus on phosphatidylcholine lipid bilayers, which out of all model membranes have been studied mostly by experiments and simulations, leading to the largest available dataset. From the applied comparisons we conclude that the acyl chain region structure and rotational dynamics are generally well described in simulation models. Also changes with temperature, dehydration and cholesterol concentration are qualitatively correctly reproduced. However, the quality of the underlying atomistic resolution structural changes is uncertain. Even worse, when focusing on the lipid bilayer properties at the interfacial region, e.g. glycerol backbone and choline structures, and cation binding, many simulation models produce an inaccurate description of experimental data. Thus extreme care must be applied when simulations are applied to understand phenomena where the interfacial region plays a significant role. This work is done by the NMRlipids Open Collaboration project running at https://nmrlipids.blogspot.fi and https://github.com/NMRLipids. This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Róg.
Topics: Cholesterol; Lipid Bilayers; Magnetic Resonance Imaging; Molecular Dynamics Simulation; Phosphatidylcholines
PubMed: 26809025
DOI: 10.1016/j.bbamem.2016.01.019