Publications by authors named "Fabiana Lairion"

9 Publications

  • Page 1 of 1

Cannabidiol (CBD) Alters the Functionality of Neutrophils (PMN). Implications in the Refractory Epilepsy Treatment.

Pharmaceuticals (Basel) 2021 Mar 5;14(3). Epub 2021 Mar 5.

Departamento de Bioquímica Clínica, Facultad de Farmacia y Bioquímica, Instituto de Fisiopatología y Bioquímica Clínica (INFIBIOC), Universidad de Buenos Aires, Buenos Aires C1120AAF, Argentina.

Cannabidiol (CBD), a lipophilic cannabinoid compound without psychoactive effects, has emerged as adjuvant of anti-epileptic drugs (AEDs) in the treatment of refractory epilepsy (RE), decreasing the severity and/or frequency of seizures. CBD is considered a multitarget drug that could act throughout the canonical endocannabinoid receptors (CB1-CB2) or multiple non-canonical pathways. Despite the fact that the CBD mechanism in RE is still unknown, experiments carried out in our laboratory showed that CBD has an inhibitory role on P-glycoprotein excretory function, highly related to RE. Since CB2 is expressed mainly in the immune cells, we hypothesized that CBD treatment could alter the activity of polymorphonuclear neutrophils (PMNs) in a similar way that it does with microglia/macrophages and others circulating leukocytes. In vitro, CBD induced PMN cytoplasmatic vacuolization and proapoptotic nuclear condensation, associated with a significantly decreased viability in a concentration-dependent manner, while low CBD concentration decreased PMN viability in a time-dependent manner. At a functional level, CBD reduced the chemotaxis and oxygen consumption of PMNs related with superoxide anion production, while the singlet oxygen level was increased suggesting oxidative stress damage. These results are in line with the well-known CBD anti-inflammatory effect and support a potential immunosuppressor role on PMNs that could promote an eventual defenseless state during chronic treatment with CBD in RE.
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http://dx.doi.org/10.3390/ph14030220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001508PMC
March 2021

Supplementation with Resveratrol, Piperine and Alpha-Tocopherol Decreases Chronic Inflammation in a Cluster of Older Adults with Metabolic Syndrome.

Nutrients 2020 Oct 15;12(10). Epub 2020 Oct 15.

Unidad Polifenoles, Vino y Salud, Cuarta Cátedra de Medicina, Hospital de Clínicas "José de San Martín" Facultad de Medicina, Universidad de Buenos Aires, City of Buenos Aires C1120AAF, Argentina.

Metabolic Syndrome (MetS) is increasing worldwide regardless of culture, genetic, gender, and geographic differences. While multiple individual risk factors, such as obesity, hypertension, diabetes, and hyperlipidemia, can cause cardiovascular disease (CVD), it is the intercurrence of these risk factors that defines MetS as a cluster that creates an environment for atherosclerosis and other manifestations of CVD. Despite the advances in the knowledge and management of each of the components of MetS, there are two molecular biology processes, chronic inflammation and oxidative stress, which are still underdiagnosed and undertreated. In order to assess the effect of a dietary supplement on chronic inflammation in MetS, we conducted a clinical trial with volunteers receiving a formula composed of resveratrol, piperine and alpha tocopherol (FRAMINTROL), together with their habitual treatment, for three months. The inflammatory state was evaluated by ultrasensitive C reactive protein (US CRP) and ferritin in plasma, and oxygen consumption and chemiluminescence in neutrophils. The results showed that ferritin decreased by 10% ( < 0.05), US-CRP by 33% ( < 0.0001), oxygen consumption by 55% ( < 0.0001), and spontaneous chemiluminiscence was by 25% ( < 0.005) after treatment. As far as we know, this is the first study showing a chronic inflammation decrease in MetS patients due to the administration of a biopower Resveratrol-piperine and alpha tocopherol dietary supplement together with conventional therapy.
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http://dx.doi.org/10.3390/nu12103149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602615PMC
October 2020

Molecular dynamics study of the interaction of arginine with phosphatidylcholine and phosphatidylethanolamine bilayers.

J Phys Chem B 2012 Apr 6;116(15):4476-83. Epub 2012 Apr 6.

Institut Pasteur de Montevideo, Montevideo, Uruguay.

In this work, the differential interaction of zwitterionic arginines with fully hydrated dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE) bilayers was analyzed by molecular dynamics simulations. In both systems, arginine binds to lipids with the carboxylate moiety oriented toward the aqueous phase, in agreement with previous experimental determinations of ζ potential of DMPC and DMPE liposomes. The guanidinium groups are found at different depths within the bilayers indicating that some arginines are buried, especially in DMPE. We observe, in the DMPE system, that the strongest interaction occurs between the guanidinium group and the carbonyl oxygen of the lipid. In the case of DMPC membranes, the strongest interaction is found between the guanidinium groups of the arginines and the phosphate groups of the lipids. Unexpectedly, arginine zwitterions are stabilized through the creation of hydrogen bonds (HB), either with water or with polar groups of the lipids. The mechanisms of interaction seem to be different in both membranes. In DMPE bilayers, arginines insert by breaking the inner HB network of the polar head groups, consequently increasing the occupied area per lipid molecule. In the DMPC bilayers the arginines insert by replacing the already present water molecules within the membrane, without significant effects on the area per lipid.
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http://dx.doi.org/10.1021/jp2096357DOI Listing
April 2012

Methylation of ethanolamine groups in phosphoethanolamines is relevant for L-arginine insertion in lipid membranes.

Biochim Biophys Acta 2012 May 17;1818(5):1395-401. Epub 2012 Feb 17.

Laboratorio de Fisicoquímica de Membranas Lipídicas, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956 2°P (1113) Buenos Aires, Argentina.

The interaction of L-arginine with membranes composed by phospholipids with different degrees of methylation of the ethanolamine group was studied by means of surface and dipole potentials and surface pressure variations. The subsequent methylation of the amine head group appears to hinder the synergic response of the adsorption observed in phosphatidylethanolamine membranes. The kinetics of the binding process denotes that the methyl groups are relevant in regulating the specific interaction of the amino acid with the interface by hydrogen bonds. This response can be put in correlation with the function of signal transduction assigned previously to methyl lipids [F. Hirata and J. Axelrod, 1980] and appears to be relevant to understand the mechanism of insertion of arginine residues in peptides of biological interest.
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http://dx.doi.org/10.1016/j.bbamem.2012.02.011DOI Listing
May 2012

Role of guanidinium group in the insertion of l-arginine in DMPE and DMPC lipid interphases.

Biochim Biophys Acta 2010 Mar 6;1798(3):616-23. Epub 2009 Nov 6.

Laboratorio de Fisicoquímica de Membranas Lipídicas, U. B. A. Junín 956 2 degrees P (1113) Buenos Aires, Argentina.

l-Arginine (Arg) is a positively charged amino acid constituent of peptides and proteins, participating in diverse mechanisms of protein-membrane interaction. The effect of Arg on phosphatidylcholine (PC) membranes has been previously related to water structure changes and to the presence of water defects in the hydrocarbon region. However, no information is available with regard to phosphatidylethanolamine (PE), another important component of lipid membranes. For this reason, the aim of this study is to determine the effect of Arg on DMPE membranes and partially methylated PEs in comparison to DMPC. The adsorption of the amino acid onto the lipid membranes was followed by determining the changes in the surface potential as a function of the bulk amino acid concentrations. The effects of Arg on the surface properties were also measured by changes in the surface pressure and the dipole potential. The onset of the transition temperature was measured with a fluorophore anchored at the membrane interphase. The results provide a new insight on amino acid-PE interactions, which can be ascribed to specific perturbations in the head group region induced by the guanidinium residue.
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http://dx.doi.org/10.1016/j.bbamem.2009.10.019DOI Listing
March 2010

Interaction of nicotinamide and picolinamide with phosphatidylcholine and phosphatidylethanolamine membranes: a combined approach using dipole potential measurements and quantum chemical calculations.

Biochim Biophys Acta 2009 Dec 17;1788(12):2553-62. Epub 2009 Oct 17.

Department of Chemistry, University of Coimbra, Portugal.

Interaction between the bioactive compounds nicotinamide and picolinamide and phospholipids (phosphatidylcholines and phosphatidylethanolamines) was investigated by a combined approach using dipole potential measurements and quantum chemical calculations. It is shown that nicotinamide and picolinamide interactions with phosphatidylcholines are of two main types: (i) specific interactions with the phosphate group of the lipid, for which H-bonding between NH(2) group of the substrate and the phosphate plays a dominant role, (ii) conjugated less specific weaker interactions involving both the phosphate and carbonyl groups of the head group, which propagate to the lipid alkyl chains and increase their conformational disorder. For phosphatidylethanolamines, picolinamide was found to decrease the dipole potential of the membrane in a similar way as for phosphatidylcholines, while nicotinamide is ineffective. These findings are correlated with the specific properties of phosphatidylethanolamines (reduced exposure of phosphate groups) and structural differences in the two substrates, in particular: different separation of the nitrogen atoms in the molecules, existence of a strong intramolecular hydrogen bond in picolinamide (NH...N ((ring))), which is absent in nicotinamide, and non-planarity of nicotinamide molecules, in contrast to picolinamide ones. Additional information on the lipid/substrate interactions was extracted from the analysis of the changes produced in the relevant vibrational frequencies of the lipid and substrate upon binding. The present study gives molecular support to the argument that changes of dipole potentials are due to effects on the constitutive dipolar PO and CO groups. In addition, it is also shown that according to the specific binding of the substrate to one or both of those, the conformational state of the acyl chains may be affected. These entropy effects may be in the origin of the well-known interdependence of the properties of one monolayer with respect to the other in bilayer membranes.
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http://dx.doi.org/10.1016/j.bbamem.2009.10.007DOI Listing
December 2009

Effect of trehalose on the contributions to the dipole potential of lipid monolayers.

Chem Phys Lipids 2007 Dec 1;150(2):117-24. Epub 2007 Jul 1.

Laboratorio de Fisicoquímica de Membranas Lipídicas y Liposomas, Cátedra de Química General e Inorgánica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956 2(o) Piso (1113), Capital Federal, Argentina.

The dipole potential and the area changes induced by trehalose on dimyristoyl phosphatidylcholine (DMPC), 1,2-di-O-tetradecyl-sn-glycero-3-phosphocholine (dietherPC), dimyristoyl phosphatidylethanolamine (DMPE), 1,2-di-O-tetradecyl-sn-glycero-3-phosphoethanolamine (dietherPE) monolayers have been studied at different temperatures. The insertion of trehalose into DMPC monolayers in the fluid and gel states requires of the presence of carbonyl groups. The area increase observed at 0.15M trehalose is congruent with the decrease in the dipole potential. However, in dietherPC, in which trehalose does not affect the area, a decrease in the dipole potential is also observed. This is interpreted as a result of the displacement of water from the phosphate groups exposed to the aqueous phase. In DMPE, trehalose also decreases the dipole potential without affecting the area of saturated monolayers and in dietherPE no effect on dipole potential and area was observed. It is concluded that the spacer effect of trehalose depends on the specific interaction with CO, which is modulated by the strength of the interaction of the PO groups with lateral NH groups. However, it is not the only contribution to the dipole potential decrease.
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http://dx.doi.org/10.1016/j.chemphyslip.2007.06.221DOI Listing
December 2007

Effect of arbutin on the dipole potential and area per lipid of ester and ether phosphatidylcholine and phosphatidyl ethanolamine monolayers.

Biochim Biophys Acta 2007 Mar 16;1768(3):450-6. Epub 2006 Dec 16.

Laboratorio de Fisicoquímica de Membranas Lipídicas y Liposomas, Cátedra de Química General e Inorgánica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956 20 Piso (1113), Capital Federal, Argentina.

The present results report for the first time a systematic study of the effect of arbutin on the dipole potential of lipid membranes. The dipole potential and the area per lipid were measured in monolayers of dimyristoylphosphatidylcholine (DMPC), 1,2-di-O-tetradecyl-sn-glycero-3-phosphocholine (dietherPC), dimyristoylphosphatidylethanolamine (DMPE) and 1,2-di-O-tetradecyl-sn-glycero-3-phosphoethanolamine (dietherPE), spread on aqueous solutions of different concentrations of arbutin. The decrease of the dipole potential of DMPC, both in condensed and expanded monolayers, is parallel to an increase in the area per lipid. In contrast, for dietherPC, the area per lipid is not affected, in spite of the fact that arbutin is also able to decrease the dipole potential in a less drastic extent. In the case of DMPE, the response is similar to that observed with dietherPC: the dipole potential decreases, while the area per lipid remains unchanged. However, when the carbonyl groups are absent in phosphatidylethanolamine derivatives such as the dietherPE, the dipole potential is not affected by arbutin, with a small decrease in the area. The effect of arbutin on the dipole potential differs from that of sucrose, trehalose and phloretin and is congruent with previous results obtained by FTIR on its interaction with the CO groups. Arbutin binding is interpreted in terms of the exposure to water of the phosphate and carbonyl groups at the membrane interface of the different monolayers.
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http://dx.doi.org/10.1016/j.bbamem.2006.11.022DOI Listing
March 2007

Effect of phloretin on the dipole potential of phosphatidylcholine, phosphatidylethanolamine, and phosphatidylglycerol monolayers.

Langmuir 2004 Oct;20(21):9151-5

Laboratorio de Fisicoquímica de Membranas Lipídicas y Liposomas, Cátedra de Química General e Inorgánica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956 2 degrees Piso (1113), Capital Federal, Argentina.

The effect of phloretin on the potential of phosphatidylcholine (PC), phosphatidylethanolamine (PE,) and phosphatidylglycerol (PG) monolayers below and above the phase transition in mixtures of different PC/PE ratios with and without cholesterol of ester and ether phospholipids have been determined. The effectiveness of phloretin to decrease the dipole potential of monolayers in the fluid state is lessened by the moieties esterified to the phosphate group in the sequence choline > ethanolamine > glycerol. These effects on the dipole potential of monolayers are independent of the presence of carbonyls. In addition, in the gel state phloretin does not affect the dipole potential on dimyristoylphosphatidylethanolamine, although it is very pronounced in dimyristoylphosphatidylcholine. The changes of the dipole potential induced by phloretin were correlated with the packing of the lipids and with the formation of intermolecular hydrogen bonds between adjacent phospholipid molecules. These results may be indicative of the different distribution of polarized water around the phosphate groups imposed by the surrounding environment.
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http://dx.doi.org/10.1021/la049515kDOI Listing
October 2004
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