Publications by authors named "Constantinos A Demopoulos"

42 Publications

Micronutrients, Phytochemicals and Mediterranean Diet: A Potential Protective Role against COVID-19 through Modulation of PAF Actions and Metabolism.

Nutrients 2021 Jan 30;13(2). Epub 2021 Jan 30.

Laboratory of Biology, Biochemistry and Microbiology, Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, 70 El. Venizelou Street, 17671 Athens, Greece.

The new coronavirus disease 2019 (COVID-19) pandemic is an emerging situation with high rates of morbidity and mortality, in the pathophysiology of which inflammation and thrombosis are implicated. The disease is directly connected to the nutritional status of patients and a well-balanced diet is recommended by official sources. Recently, the role of platelet activating factor (PAF) was suggested in the pathogenesis of COVID-19. In the present review several micronutrients (vitamin A, vitamin C, vitamin E, vitamin D, selenium, omega-3 fatty acids, and minerals), phytochemicals and Mediterranean diet compounds with potential anti-COVID activity are presented. We further underline that the well-known anti-inflammatory and anti-thrombotic actions of the investigated nutrients and/or holistic dietary schemes, such as the Mediterranean diet, are also mediated through PAF. In conclusion, there is no single food to prevent coronavirus Although the relationship between PAF and COVID-19 is not robust, a healthy diet containing PAF inhibitors may target both inflammation and thrombosis and prevent the deleterious effects of COVID-19. The next step is the experimental confirmation or not of the PAF-COVID-19 hypothesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu13020462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911163PMC
January 2021

Coronavirus 2019, Microthromboses, and Platelet Activating Factor.

Clin Ther 2020 10 17;42(10):1850-1852. Epub 2020 Aug 17.

Laboratory of Biochemistry, Faculty of Chemistry, National & Kapodistrian University of Athens, Athens, Greece.

Recent articles have reported elevated markers of coagulation, endothelial injury, and microthromboses in lungs from deceased patients with coronavirus 2019 (COVID-19). Platelets are critical in the formation of thrombi, and their most potent trigger is platelet activating factor (PAF). PAF is produced by cells involved in host defense, and its biological actions bear similarities with COVID-19 disease manifestations, including pulmonary microthromboses and inflammation, possibly via activation of mast cells. The histamine receptor antagonist rupatadine was developed to have anti-PAF activity and inhibits activation of human mast cells in response to PAF. Rupatadine could be repurposed for COVID-19 prophylaxis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinthera.2020.08.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430296PMC
October 2020

Forty Years Since the Structural Elucidation of Platelet-Activating Factor (PAF): Historical, Current, and Future Research Perspectives.

Molecules 2019 Dec 3;24(23). Epub 2019 Dec 3.

Department of Chemistry, National and Kapodistrian University of Athens, Panepistimioupolis, 15771 Athens, Greece.

In the late 1960s, Barbaro and Zvaifler described a substance that caused antigen induced histamine release from rabbit platelets producing antibodies in passive cutaneous anaphylaxis. Henson described a 'soluble factor' released from leukocytes that induced vasoactive amine release in platelets. Later observations by Siraganuan and Osler observed the existence of a diluted substance that had the capacity to cause platelet activation. In 1972, the term platelet-activating factor (PAF) was coined by Benveniste, Henson, and Cochrane. The structure of PAF was later elucidated by Demopoulos, Pinckard, and Hanahan in 1979. These studies introduced the research world to PAF, which is now recognised as a potent phospholipid mediator. Since its introduction to the literature, research on PAF has grown due to interest in its vital cell signalling functions and more sinisterly its role as a pro-inflammatory molecule in several chronic diseases including cardiovascular disease and cancer. As it is forty years since the structural elucidation of PAF, the aim of this review is to provide a historical account of the discovery of PAF and to provide a general overview of current and future perspectives on PAF research in physiology and pathophysiology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules24234414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930554PMC
December 2019

Wine and its metabolic effects. A comprehensive review of clinical trials.

Metabolism 2018 06 3;83:102-119. Epub 2018 Feb 3.

Department of Chemistry, National and Kapodistrian University of Athens, Panepistimioupolis, 15771 Athens, Greece.

The introduction of the term "French Paradox" motivated an extensive and in-depth research into health benefits of moderate wine consumption. The superiority of wine is thought to be attributed to its micro-constituents and consequent effort was made to isolate and identify these bioactive compounds as well as to elucidate the mechanisms of their action. Controlled trials offer more concrete answers to several raised questions than observational studies. Under this perspective, clinical trials have been implemented, mainly in healthy volunteers and rarely in patients, in order to investigate the acute or chronic effect of wine consumption on metabolism and physio-pathological systems, which are mainly associated with cardiovascular diseases. The aim of this review is to update the knowledge about the acute and long term effect of wine consumption on lipid and glucose/insulin metabolism as well as on the inflammatory and haemostatic systems, based on the reported data of controlled clinical trials. In conclusion, the most repeated result of wine consumption is on lipid metabolism, attributed mainly to ethanol, while wine micro-constituents seem to have an important role mainly in haemostatic and inflammatory/endothelial systems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.metabol.2018.01.024DOI Listing
June 2018

A Review on Platelet Activating Factor Inhibitors: Could a New Class of Potent Metal-Based Anti-Inflammatory Drugs Induce Anticancer Properties?

Bioinorg Chem Appl 2017 28;2017:6947034. Epub 2017 Mar 28.

Laboratory of Inorganic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771 Athens, Greece.

In this minireview, we refer to recent results as far as the Platelet Activating Factor (PAF) inhibitors are concerned. At first, results of organic compounds (natural and synthetic ones and specific and nonspecific) as inhibitors of PAF are reported. Emphasis is given on recent results about a new class of the so-called metal-based inhibitors of PAF. A small library of 30 metal complexes has been thus created; their anti-inflammatory activity has been further evaluated owing to their inhibitory effect against PAF in washed rabbit platelets (WRPs). In addition, emphasis has also been placed on the identification of preliminary relationships for the different classes of metal-based inhibitors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2017/6947034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5387815PMC
March 2017

Postprandial effects of wine consumption on Platelet Activating Factor metabolic enzymes.

Prostaglandins Other Lipid Mediat 2017 05 16;130:23-29. Epub 2017 Mar 16.

Department of Nutrition and Dietetics, Harokopio University, 70 Eleftheriou Venizelou Avenue Kallithea, 17671, Athens, Greece. Electronic address:

Platelet Activating factor (PAF) is a potent inflammatory mediator that is involved in the initiation and the prolongation of atherosclerosis. The purpose of the study was to investigate the effect of wine consumption on the activity of PAF metabolic enzymes and on IL-6 levels as a cytokine inflammatory marker. Healthy men participated in 4 daily trials and consumed a standardized meal along with Robola wine (trial R), or Cabernet Sauvignon (trial CS), or ethanol solution (trial E), or water (trial W). A significant trial effect was found in the activity of lyso-PAF acetyltransferase (Lyso-PAF AT) (p=0.01). In specific, R trial decreased enzyme activity compared to E trial (p=0.03) while a trend for differentiation was observed between CS trial and E one (p=0.06) as well as between R trial and W one (p=0.07). Concerning PAF-cholinephosphotransferase (PAF-CPT) activity, a significant trial effect was found (p<0.00). Specifically, both R (p=0.002) and CS (p=0.001) trials decreased enzyme activity compared to E trial. Concerning lipoprotein-associated phospholipase A2 (LpPLA2) no time either trial effect was observed. Concerning IL-6 levels a significant time effect was found (p<0.00) while no trial effect was revealed. In conclusion, the protective effect of wine consumption could partly be explained through the modulation of PAF metabolism by wine micro-constituents that lead to lower PAF levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prostaglandins.2017.03.002DOI Listing
May 2017

Impact of prostaglandin glaucoma drops on platelet-activating factor action: an in vitro study.

Drug Des Devel Ther 2016 7;10:3977-3981. Epub 2016 Dec 7.

Laboratory of Biochemistry, National and Kapodistrian University of Athens, Athens, Greece.

Aim: The aim of this study was to investigate the effect of different prostaglandin analogs on platelet-activating factor (PAF) levels.

Methods: Three prostaglandin analogs were selected: bimatoprost 0.3 mg/mL, latanoprost 50 μg/mL, and tafluprost 15 μg/mL. Each drug sample was tested for its ability to cause platelet aggregation, which was measured as PAF-induced aggregation, before and after the addition of various concentrations of the examined sample, creating a linear curve of percentage inhibition (ranging from 0% to 100%) versus different concentrations of the sample. The concentration of the sample that inhibited 50% PAF-induced aggregation was calculated based on this curve, and this value was defined as IC50. In addition, the effect of eye drops on PAF metabolism was examined, through an in vitro analysis on PAF basic metabolic enzymes (PAF-cholinephosphotransferase, PAF-acetyl-CoA:1-O-alkyl-sn-glycero-3-phosphocholine acetyltransferase, and PAF-acetylhydrolase).

Results: The IC50 values for Lumigan UD (bimatoprost 0.3 mg/mL), Monoprost (latanoprost 50 μg/mL), and Saflutan (tafluprost 15 μg/mL) were 8.7, 0.28, and 1.4 μg/mL, respectively.

Discussion: All three prostaglandin analogs suspended PAF, but bimatoprost induced the most potent inhibition, compared to tafluprost and to the weak effect of latanoprost.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/DDDT.S117806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5153256PMC
March 2017

In Vitro Effects of Anti-Glaucomatous Eye Drops on Platelet-Activating Factor and its Metabolism.

Semin Ophthalmol 2017 13;32(2):198-203. Epub 2015 Aug 13.

b Laboratory of Biochemistry, Faculty of Chemistry , University of Athens , Athens , Greece , and.

Purpose: The purpose of this study is to determine the effect of various commonly used antiglaucoma eye drops on inflammatory mediators such as the platelet activating factor (PAF).

Methods: Various intraocular pressure (IOP) lowering drops were tested to examine their inhibitory effect on PAF. Multiple eye drops were tested in washed rabbit platelets (WRPs) in order to determine the interaction between these eye drops and the inhibition of PAF in the PAF-induced platelet aggregation model. In addition, we examined the eyedrops' effect on PAF-metabolism, through in vitro analysis on PAF basic metabolic enzymes (PAF-CPT, lyso PAF-AT, and PAF-AH).

Results: Latanoprost (Xalatan) was found to be the most potent in inhibiting PAF, suggesting that it is the most effective in decreasing IOP amongst the eye drops tested. Conversely, dorzolamide hydrochloride-timolol (Cosopt) exhibited the least anti-PAF action.

Conclusions: This is the first study examine the relationship between PAF activity and glaucoma medication. Potency in PAF inhibition may be related to drop efficacy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/08820538.2015.1053622DOI Listing
March 2017

In vivo effect of two first-line ART regimens on inflammatory mediators in male HIV patients.

Lipids Health Dis 2014 May 29;13:90. Epub 2014 May 29.

Faculty of Chemistry, National & Kapodistrian University of Athens, Panepistimioupolis Zografou, 15771 Athens, Greece.

Background: Persistent immune activation and inflammation are lying behind HIV-infection even in the setting of ART mediated viral suppression. The purpose of this study is to define the in vivo effect of two first-line ART regimens on certain inflammatory mediators in male HIV patients.

Methods: Male, naive, HIV-infected volunteers were assigned either to tenofovir-DF/emtricitabine/efavirenz (Group_T) or abacavir/lamivudine/efavirenz (Group_A). Platelet Activating Factor (PAF) levels and metabolic enzymes together with HIV-implicated cytokines (IL-1beta, IL-6, IL-8, IL-10, IL-12p70, TNFa) and VEGF were determined for a 12-month period. Differences within each group were determined by non-parametric Friedman and Wilcoxon test, while the differences between the groups were checked by ANOVA repeated measures.

Results: Both ART regimens present pronounced effect on inflammatory mediators, resulting in decreased PAF levels and Lipoprotein-associated phospholipase A2 (Lp-PLA2) activity for tenofovir-containing regimen and same as baseline PAF levels with a peak though at the 3rd month as well as elevated Lp-PLA2 activity for abacavir-containing regimen.

Conclusions: Studies regarding the effect of first-line ART regimens on inflammation may be beneficial in preventing chronic morbidities during HIV-treatment. From this point of view, the present study suggests an anti-inflammatory effect of tenofovir-containing ART, while the temporary increase of PAF levels in abacavir-containing ART may be the link between the reported cardiovascular risk and abacavir administration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1476-511X-13-90DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4055908PMC
May 2014

Re(I) tricarbonyl complex of 1,10-phenanthroline-5,6-dione: DNA binding, cytotoxicity, anti-inflammatory and anti-coagulant effects towards platelet activating factor.

J Inorg Biochem 2014 Jun 17;135:1-9. Epub 2014 Feb 17.

Laboratory of Inorganic Chemistry, Faculty of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 157 71 Athens, Greece. Electronic address:

The complex fac-[Re(CO)3(phendione)Cl] (1) (where phendione=1,10-phenanthroline-5,6-dione) has been synthesized and fully characterized by UV-visible, FTIR, and NMR techniques. The DNA binding properties of 1 are investigated by UV-spectrophotometric (melting curves), covalent binding assay, CV (cyclic voltammetry), circular dichroism (CD) and viscosity measurements. Experimental data indicate that 1 fits into the major groove without disrupting the helical structure of the B-DNA in contrast to the free phendione which intercalates within the base pairs of DNA. Upon irradiation, complex 1 promotes the cleavage of plasmid pBR322 DNA from supercoiled form I to nicked form II via a proton coupled electron transfer mechanism. This comes as a result of experimental data in anaerobic/aerobic conditions and in the presence of DMSO. The biological activities of 1 and its precursors [Re(CO)5Cl] and phendione are tested towards a series of cancerous cell lines as glioblastoma (T98G), prostate cancer (PC3) and breast cancer (MCF-7) as well as platelet activating factor (PAF)-aggregation. Moreover, all the aforementioned compounds are tested for their ability to modulate PAF-basic metabolic enzyme activities in preparations of rabbit leukolytes. The in vitro experiments indicate that phendione has a better antitumor effect than cisplatin whereas [Re(CO)5Cl] is a better PAF inhibitor than both the phendione ligand and 1. Moreover, for the first time it is indicated that [Re(CO)5Cl], with a IC50 of 17nM is comparable to the widely used PAF receptor antagonists, BN52021 and WEB2170 with IC50 of 30 and 20nM, respectively, whereas 1 affects PAF-catabolism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jinorgbio.2014.02.003DOI Listing
June 2014

In vitro effects of vitamin supplements on platelet-activating factor and its metabolism in age-related macular degeneration.

Cutan Ocul Toxicol 2014 Sep 22;33(3):235-41. Epub 2013 Oct 22.

Laboratory of Electrophysiology, 1st Department of Ophthalmology, University of Athens , Athens , Greece and.

Objective: The purpose of our study was to investigate for the first time a series of vitamin supplements used for age-related macular degeneration (AMD) as potential inhibitors of platelet-activating factor (PAF).

Materials And Methods: Various vitamin supplements were tested in washed rabbit platelets (WRPs), in order to investigate the interaction between vitamin supplements (InShape, Nutrof, Ocuvite, Vitalux) and inhibition of PAF-induced platelet aggregation. Additionally, we examined their ability to affect PAF-metabolism, through their in vitro effect on PAF basic metabolic enzymes (PAF-CPT, lyso PAF-AT, and PAF-AH).

Results: Nutrof exhibited the strongest anti-PAF activity, while Vitalux was the most potent anti-inflammatory factor.

Conclusion: This is the first study to bring in surface potent anti-inflammatory and anti-angiogenic activities of some vitamin supplements used against AMD, through their in vitro anti-PAF effects in WRPs and the rabbit plasma and leukocyte PAF metabolism, suggesting a promising role of vitamin supplements and especially resveratrol, concerning its potent anti-angiogenic activity in AMD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/15569527.2013.835818DOI Listing
September 2014

Evaluation of the in vitro anti-atherogenic properties of lipid fractions of olive pomace, olive pomace enriched fish feed and gilthead sea bream (Sparus aurata) fed with olive pomace enriched fish feed.

Mar Drugs 2013 Sep 30;11(10):3676-88. Epub 2013 Sep 30.

Laboratory of Food Chemistry, Faculty of Chemistry, School of Sciences, National and Kapodistrian University of Athens, Athens 15771, Greece.

Given the pivotal role of Platelet-Activating-Factor (PAF) in atherosclerosis and the cardio-protective role of PAF-inhibitors derived from olive pomace, the inclusion of olive pomace in fish feed has been studied for gilthead sea bream (Sparus aurata). The aim of the current research was to elucidate the anti-atherogenic properties of specific HPLC lipid fractions obtained from olive pomace, olive pomace enriched fish feed and fish fed with the olive pomace enriched fish feed, by evaluating their in vitro biological activity against washed rabbit platelets. This in vitro study underlines that olive pomace inclusion in fish feed improves the nutritional value of both fish feed and fish possibly by enriching the marine lipid profile of gilthead sea bream (Sparus aurata) with specific bioactive lipid compounds of plant origin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/md11103676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3826129PMC
September 2013

Interleukin-1beta stimulates platelet-activating factor production in U-937 cells modulating both its biosynthetic and catabolic enzymes.

Cytokine 2013 Aug 11;63(2):97-104. Epub 2013 May 11.

Faculty of Chemistry, National and Kapodistrian University, Athens, Greece.

Interleukin-1beta (IL-1β) is a potent agonist of platelet-activating factor (PAF) synthesis. The monocyte-derived PAF may amplify the inflammatory and thrombotic processes. The IL-1β-induced enzymatic alterations leading to increased PAF synthesis are ill-defined. In the present study the last enzymatic activities of the remodeling (acetyl-CoA:lyso-PAF acetyltransferase) and de novo (DTT-insensitive CDP-choline:1-alkyl-2-acetyl-sn-glycerol cholinephosphotransferase) biosynthetic routes of PAF and its main catabolic enzyme, PAF acetylhydrolase, along with the intracellular and extracellular PAF levels were determined in homogenates and medium of U-937 after their stimulation with recombinant IL-1β. IL-1β at 2.5ng/mL induced an early (0.5-3h) and a late (12h) elevation of intracellular PAF levels (2-fold). Only a small portion of intracellular PAF (∼10%) was released to the extracellular medium. IL-1β increased lyso-PAF acetyltrasnferase activity which was peaked at 3h and kept elevated till 12h. A rapid 1.5-fold increase of cholinephosphotransferase activity was observed in IL-1β stimulated cells. Finally, a transient stimulation of intracellular PAF-AH was induced by IL-1β at 3h while incubation of U-937 with the PAF acetylhydrolase inhibitor pefabloc in the presence or absence of IL-1β led to a strong sustained increase of intracellular PAF levels. In conclusion, both biosynthetic routes of PAF, along with its degradation can be modulated by IL-1β in a time-specific manner. The inhibition of PAF acetylhydrolase strongly augments PAF's intracellular levels implying its crucial role for the regulation of cellular PAF. The regulation of PAF's enzymatic machinery under inflammatory conditions is more complicated than we thought to be.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cyto.2013.04.024DOI Listing
August 2013

Paricalcitol effects on activities and metabolism of platelet activating factor and on inflammatory cytokines in hemodialysis patients.

Int J Artif Organs 2013 Feb;36(2):87-96

Faculty of Chemistry, National & Kapodistrian University of Athens, Panepistimioupolis, Athens - Greece.

Purpose: Paricalcitol improves the inflammatory status of hemodialysis patients. PAF is a strong inflammatory mediator which is produced during hemodialysis. We studied the effects of paricalcitol on PAF and other inflammatory mediators implicated in chronic kidney disease (CKD).

Methods: We examined the in vitro effects of paricalcitol on PAF/thrombin-induced aggregation as well as on the activities of PAF-basic metabolic enzymes, lyso-PAF acetyltransferase (Lyso-PAF-AT), DTT-insensitive CDP-choline: 1-alkyl-2-acetyl-sn-glycerol cholinephospho-transferase (PAF-CPT) and PAF-acetylhydrolase (PAF-AH) in blood cells from healthy volunteers. In addition, the in vivo effects of paricalcitol on the above these enzymes were examined in plasma and blood cells of hemodialysis patients who had not received any type of vitamin D treatment during the last three months before and after receiving paricalcitol for a month. Finally, IL-12p70, IL-1β, IL-6, IL-8 and TNF-α were measured.

Results: Paricalcitol inhibited in vitro PAF/thrombin-induced platelet aggregation and the inhibitory effect was comparable with that of PAF/thrombin antagonists. In addition, paricalcitol inhibited in vitro PAF-CPT activity in platelets and leukocytes and increased PAF-AH activity in leukocytes, while much higher concentrations of paricalcitol were needed to inhibit Lyso-PAF-AT activity. Similarly, in hemodialysis patients, paricalcitol treatment reduced PAF-CPT activity in platelets and leukocytes and increased PAF-AH activity in leukocytes, while it could not influence Lyso-PAF-AT activity. On the other hand, paricalcitol therapy reduced IL-8, IL-1β, and TNF-α.

Conclusions: These results further support the beneficial effects of vitamin D treatment in hemodialysis patients, since it strongly affects PAF/thrombin activities, PAF-metabolism, and IL-8, IL-1β and TNF-α circulating levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5301/ijao.5000187DOI Listing
February 2013

Synthesis, biochemical evaluation and molecular modeling studies of novel rhodium complexes with nanomolar activity against Platelet Activating Factor.

J Inorg Biochem 2013 Mar 19;120:63-73. Epub 2012 Dec 19.

Laboratory of Biochemistry, Faculty of Chemistry, National and Kapodistrian University of Athens, Athens 15771, Greece.

Two square planar Rh(I) organometallic complexes namely [Rh(L(1))(cod)]Cl (cod = cycloocta-1,5-diene, L(1)=2,2'-pyridylquinoxaline (1-Cl), [Rh(L1)(cod)](NO3) (1-NO(3)) and a series of novel octahedral rhodium(III) complexes of the general formulae mer-[Rh(L(1))Cl(3)(MeOH)] (2) and cis-[Rh(L(2))(2)Cl(2)]Cl (L(2)=4 carboxy 2 (2' pyridyl)quinoline (3), L(3)=2,2' bipyridine 4,4' dicarboxylic acid (4) were synthesized and characterized spectroscopically. All the synthesized compounds including the previously prepared cis-[Rh(L(1))(2)Cl(2)]Cl complex (5) were biologically evaluated as potential inhibitors of the Platelet Activation Factor (PAF) and thrombin induced aggregation. In particular compounds 1-Cl and 1-NO(3) were found to be strong inhibitors of PAF with IC(50) values in the range of 16 nM and 15 nM rendering them good candidates for further investigation. Their potency is comparable to that of the widely used PAF receptor antagonists WEB2170, BN52021, and Rupatadine (IC(50) of 20, 30 and 260 nM respectively). Molecular docking calculations suggest that 1-Cl, 1-NO3 and 2 can be accommodated within the ligand-binding site of PAF receptor and block the activity of PAF. On the other hand, the octahedral rhodium(III) complexes 3-5 that cannot fit the ligand-binding domain, could potentially exhibit their activity at the extracellular domain of the receptor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jinorgbio.2012.12.004DOI Listing
March 2013

Platelet activating factor levels and metabolism in Tangier disease: a case study.

Lipids Health Dis 2012 Jul 8;11:89. Epub 2012 Jul 8.

Cardiology Department and Molecular Immunology Laboratory, Onassis Cardiac Surgery Center, Athens, Greece.

Background: Tangier disease (TD) is a phenotypic expression of rare familial syndrome with mutations in the ABCA1 transporter. The risk of coronary artery disease in patients with TD is variable. On the other hand the pivotal role of Platelet-Activating Factor (PAF) mediator in atheromatosis was found. Plasma lipoproteins are transporters of the PAF acetylhydrolase (PAF-AH) in cells and known as lipoprotein-phospholipase A2 (Lp-PLA2) in plasma and regulators of PAF levels in blood. In addition, PAF can be biosynthesized from the remodeling and the de novo pathways in which Lyso-platelet activating factor-acetyltransferase (Lyso-PAF-AT) and platelet activating factor-cholinephosphotransferase (PAF-CPT) are the regulatory enzymes. The aim of this study is to investigate in a TD patient with a unique mutation (C2033A), the concentration of PAF in blood, the Equivalent Concentration for 50% aggregation (EC50) values of platelet rich plasma (PRP) toward PAF, adenosine diphosphate (ADP) and thrombin, and the activities of PAF metabolic enzymes Lp-PLA2, PAF-AH, Lyso-PAF-AT and PAF-CPT.

Methods: The EC50 value of PRP was measured by an aggregometer. The determination of the specific activity of PAF-CPT and Lyso-PAF-AT was made after in vitro enzymatic assay, chromatographic separation and measurement of the produced PAF in a biological assay with washed rabbit platelets. The determination of PAF-AH and Lp-PLA2 was made after an in vitro enzymatic assay from the decay of radioactive PAF.

Results: The TD patient had lower bound-PAF values in blood, decreased specific activity of PAF-CPT and Lyso-PAF-AT, increased specific activity of PAF-AH in platelets and leukocytes and Lp-PLA2 activity in plasma compared to healthy women. The EC50 of PAF and Thrombin were higher compared to healthy women.

Conclusion: The increased Lp-PLA2 activity, as well as, the decreased activities of PAF-CPT and Lyso-PAF-AT, explain the decreased bound-PAF level in TD patient and the EC50 of PAF. However, total PAF is in a normal range and this probably can explain one of the reasons this TD patient has no CAD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1476-511X-11-89DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3499335PMC
July 2012

Effects of olive pomace and olive pomace oil on growth performance, fatty acid composition and cardio protective properties of gilthead sea bream (Sparus aurata) and sea bass (Dicentrarchus labrax).

Food Chem 2011 Dec 25;129(3):1108-13. Epub 2011 May 25.

Laboratory of Food Chemistry, Faculty of Chemistry, School of Sciences, National and Kapodistrian University of Athens, Athens 15771, Greece. Electronic address:

Gilthead sea bream (Sparus aurata) and sea bass (Dicentrarchus labrax) were fed with two experimental diets: olive pomace diet and olive pomace oil diet, in order to examine whether fish oil substitution in fish feeds by olive oil production wastes, such as olive pomace and olive pomace oil, has an influence on growth performance, fatty acid composition and cardio protective properties of fish. Gilthead sea bream fed with both experimental diets exhibited satisfactory growth performance factors while sea bass did not. The total lipids of gilthead sea bream fed with olive pomace diet contained statistically decreased levels of fatty acids, while exhibited the most potent biological activity against platelet aggregation induced by Platelet Activating Factor. These data indicate that olive pomace can be used as a partial substitute of fish oil in fish feed improving its cardio protective properties.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.foodchem.2011.05.086DOI Listing
December 2011

Fish polar lipids retard atherosclerosis in rabbits by down-regulating PAF biosynthesis and up-regulating PAF catabolism.

Lipids Health Dis 2011 Nov 16;10:213. Epub 2011 Nov 16.

Department of Food and Nutrition Sciences, University of the Aegean, 2 Metropoliti Ioakim,814 00 Myrina, Lemnos, Greece.

Background: Platelet activating factor (PAF) has been proposed as a key factor and initial trigger in atherosclerosis. Recently, a modulation of PAF metabolism by bioactive food constituents has been suggested. In this study we investigated the effect of fish polar lipid consumption on PAF metabolism.

Results: The specific activities of four PAF metabolic enzymes; in leukocytes, platelets and plasma, and PAF concentration; either in blood cells or plasma were determined. Samples were acquired at the beginning and at the end of a previously conducted study in male New Zealand white rabbits that were fed for 45 days with atherogenic diet supplemented (group-B, n = 6) or not (group-A, n = 6) with gilthead sea bream (Sparus aurata) polar lipids.The specific activity of PAF-Acetylhydrolase (PAF-AH); a catabolic enzyme of PAF, was decreased in rabbits' platelets of both A and B groups and in rabbits' leukocytes of group A (p < 0.05). On the other hand the specific activity of Lipoprotein-associated Phospholipase A2 (Lp-PLA2); the catabolic enzyme of PAF in plasma was increased in both A and B groups in both leukocytes and platelets (p < 0.05). PAF-cholinephosphotransferase (PAF-CPT); a biosynthetic enzyme of PAF showed increased specific activity only in rabbits' leukocytes of group A (p < 0.05). Neither of the two groups showed any change in Lyso-PAF-acetyltransferase (Lyso-PAF-AT) specific activity (p > 0.05). Free and bound PAF levels increased in group A while decreased in group B (p < 0.05).

Conclusions: Gilthead sea bream (Sparus aurata) polar lipids modulate PAF metabolism upon atherosclerotic conditions in rabbits leading to lower PAF levels and activity in blood of rabbits with reduced early atherosclerotic lesions compared to control group.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1476-511X-10-213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3229473PMC
November 2011

Effects of HAART on platelet-activating factor metabolism in naive HIV-infected patients I: study of the tenofovir-DF/emtricitabine/efavirenz HAART regimen.

AIDS Res Hum Retroviruses 2012 Aug 22;28(8):766-75. Epub 2011 Dec 22.

3rd Internal Medicine Department-Infectious Diseases Unit, Red Cross General Hospital, Athens, Greece.

Platelet-activating factor (PAF) is implicated in human immunodeficiency virus (HIV)-related manifestations. Increased PAF synthesis has been recently detected in HIV-infected patients. In this study, we examined in naive HIV-infected patients the in vivo effects of a highly active antiretroviral therapy (HAART) regimen, containing tenofovir-DF/emtricitabine/efavirenz, on PAF metabolism. The specific activities of PAF basic biosynthetic enzymes, PAF-cholinephosphotransferase (PAF-CPT) and lyso-PAF-acetyltransferase (lyso-PAF-AT), but also the ones of PAF-basic catabolic enzymes, PAF acetylhydrolase (PAF-AH) in leukocytes and platelets, and lipoprotein-associated-phospholipase-A(2) (LpPLA(2)) in plasma, were measured in blood samples of eight asymptomatic naive male HIV-infected patients just before and after 1, 3, and 6 months of treatment. CD4 cell counts, viral load, and several biochemical markers were also measured in the same blood samples of these patients. The repeated measures ANOVA and the Pearson r criterion were used to study statistical differences and correlations-partial correlations, while linear mixed models were conducted in order to estimate association(s) between time-dependent changes in these factors. Before treatment, the activities of PAF-CPT in leukocytes and LpPLA(2) in plasma were found to be inversely correlated with CD4 cell counts and positively correlated with the viral load. After 6 months of treatment, the activities of basic PAF-biosynthetic enzymes, PAF-CPT and lyso-PAF-AT, were both reduced in leukocytes. At 6 months, PAF-AH activity was also reduced in these cells, while LpPLA(2) remained stable. The reduction of PAF-CPT occurred even from the first month, while there is a time-dependent correlation between the increase of CD4 and the decrease of both viral load and PAF-CPT of leukocytes during treatment. Apart from its classical antiretroviral activities the tenofovir-DF/emtricitabine/efavirenz regimen also exhibited favorable effects on PAF metabolism and therefore may also display beneficial effects in some HIV-related conditions, such as cardiovascular disease (CVD), in which PAF is implicated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/AID.2011.0202DOI Listing
August 2012

Platelet-activating factor and its basic metabolic enzymes in blood of naive HIV-infected patients.

Angiology 2012 Jul 22;63(5):343-52. Epub 2011 Sep 22.

Department of Chemistry, National and Kapodistrian University of Athens, Greece.

Platelet-activating factor (PAF), a mediator of proatherosclerotic inflammatory processes, is also implicated in endothelial dysfunction during human immunodeficiency virus (HIV) infection. We examined PAF metabolism in blood of naive male patients, 8 with early HIV infection (group A) and 17 just before treatment initiation (group B), versus 18 healthy age-matched males (group C). Statistical analysis was performed with 1-way analysis of variance (ANOVA) criterion and Pearson r test. Higher PAF biosynthesis in patients' leukocytes versus group C was accompanied by an increase in lipoprotein-associated phospholipase A2 (Lp-PLA2) activity that degrades PAF. Moreover, PAF synthesis was higher and Lp-PLA2 activity was lower in group B compared to group A. Lipoprotein-associated phospholipase A2 was positively correlated with viral load and negatively correlated with CD4 cell counts in group B. The activities of PAF-basic biosynthetic enzymes in patients' leukocytes were also negatively correlated with CD4 cell counts. The observed continuous increase in PAF biosynthesis during HIV infection progress seems to amplify the risk of AIDS manifestations and/or cardiovascular complications in HIV-infected patients, while a subsequent increase in Lp-PLA2 activity seems to be a host response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0003319711420608DOI Listing
July 2012

PAF effects on MCP-1 and IL-6 secretion in U-937 monocytes in comparison with oxLDL and IL-1β effects.

Atherosclerosis 2011 Dec 5;219(2):519-25. Epub 2011 Aug 5.

Faculty of Chemistry, National and Kapodistrian University of Athens, Panepistimioupolis, 15771 Athens, Greece.

Objective: To study the effects of PAF, in comparison with oxLDL and IL-1β on MCP-1 and IL-6 secretion from U-937 monocytes and to investigate the mechanism of its action.

Methods: U-937 cell line was cultured in the presence or absence of PAF or oxLDL or IL-1β. Secretion of IL-6 and MCP-1 was measured by ELISA method, mRNA levels of MCP-1 and PAFR was measured using real-time PCR. In order to investigate the mechanism of mediator's action signal transduction appropriate inhibitors was used and oxidant status of cells by measurement the total cellular thiols content and glutathione was determined.

Results And Conclusion: None of the tested mediators induced the secretion of IL-6. On the other hand PAF and oxLDL caused a short-term while IL-1β caused a long-term secretion and expression of MCP-1. Reduced total thiol levels and GSH/GSSG ratio indicate that the above mediators induce oxidative stress. The signal transduction of all mediators is mediated through G-proteins, protein kinases (PKC, serine-threonine kinase and tyrosine kinase) and NF-κB activation. In addition, PAF, oxLDL, IL-1β activates monocytes leading to increased PAF receptor mRNA levels. These results indicate that PAF and oxLDL, in a different pattern from that of IL-1β, regulate MCP-1 expression via pathways that involve changes in cell redox status.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.atherosclerosis.2011.07.123DOI Listing
December 2011

In vitro anti-inflammatory and anti-coagulant effects of antibiotics towards Platelet Activating Factor and thrombin.

J Inflamm (Lond) 2011 Jul 7;8:17. Epub 2011 Jul 7.

Faculty of Chemistry, National & Kapodistrian University of Athens, Panepistimioupolis of Zografou, Athens, 15771, Greece.

Background: Sepsis is characterized as a systemic inflammatory response that results from the inability of the immune system to limit bacterial spread during an ongoing infection. In this condition the significant mediator of inflammation Platelet Activating Factor (PAF) and the coagulant factor thrombin are implicated. In animal models, treatment with PAF-antagonists or co-administration of antibiotics with recombinant-PAF-Acetylhydrolase (rPAF-AH) have exhibited promising results. In order to examine the putative anti-inflammatory and/or antithrombotic interactions between antibiotic treatment used in sepsis with PAF and/or thrombin, we studied the in vitro effects of these compounds towards PAF or/and thrombin related activities and towards PAF basic metabolic enzymes.

Methods: We assessed the inhibitory effect of these drugs against PAF or thrombin induced aggregation on washed rabbit platelets (WRPs) or rabbit Platelet Reach Plasma (rPRP) by evaluating their IC50 values. We also studied their effect on Cholinephosphotransferase of PAF (PAF-CPT)/Lyso-PAF-Acetyltransferase (Lyso-PAF-AT) of rabbit leukocytes (RLs), as well as on rabbit plasma-PAF-AH, the key enzymes of both de novo/remodelling PAF biosynthesis and PAF degradation, respectively.

Results: Several antibiotics inhibited PAF-induced platelet aggregation of both WRPs and rPRP in a concentration-depended manner, with clarithromycin, azithromycin and amikacin exhibiting the higher inhibitory effect, while when combined they synergistically inhibited PAF. Higher concentrations of all antibiotics tested were needed in order to inhibit PAF induced aggregation of rPRP, but also to inhibit thrombin induced aggregation of WRPs. Concentrations of these drugs similar to their IC50 values against PAF activity in WRPs, inhibited also in vitro PAF-CPT and Lyso-PAF-AT activities of rabbit leukocytes, while only clarithromycin and azithromycin increased rabbit plasma-PAF-AH activity.

Conclusions: These newly found properties of antibiotics used in sepsis suggest that apart from their general actions, these drugs may present additional beneficial anti-inflammatory and anti-coagulant effects against the onset and establishment of sepsis by inhibiting the PAF/PAF-receptor and/or the thrombin/protease-activated-receptor-1 systems, and/or by reducing PAF-levels through both PAF-biosynthesis inhibition and PAF-catabolism induction. These promising in vitro results need to be further studied and confirmed by in vivo tests, in order to optimize the efficacy of antibiotic treatment in sepsis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1476-9255-8-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3162514PMC
July 2011

ATP-binding cassette transporter A1 gene polymorphisms and serum lipid levels in young Greek nurses.

Lipids Health Dis 2011 Apr 13;10:56. Epub 2011 Apr 13.

Molecular Immunology Laboratory, Onassis Cardiac Surgery Center Athens, Greece.

Objective: The ATP-binding cassette transporter A1 (ABCA1) is essential protein involved in lipid metabolism. The present study was undertaken to detect the possible association of polymorphisms in the ABCA1 gene [rs2230806 (R219K) and rs2230808 (R1587K)] and lipid profile in Greek young nurses.

Methods: The study population consisted of 308 unrelated nurses who were genotyped and the ABCA1 polymorphisms were detected. Additionally, lipid profile [total cholesterol (TC), triglycerides (TGs), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and apolipoprotein (apo) A] was evaluated.

Results: There was no difference in the genotypic and allelic frequencies of the R219K polymorphism according to lipid profile. The R1587K genotypes differed significantly according to TC, LDL-C and TGs concentration (p = 0.023, p = 0.014 and p = 0.047, respectively). Particularly, significant difference in TC, LDL-C and TGs concentration was detected between RK and RR genotypes (p = 0.006, p = 0.004, p = 0.014, respectively). Women with RK genotype compared to RR genotype had higher concentration of TGs (134.25 mg/dl vs 108.89 mg/dl, p = 0.014, respectively), total cholesterol (207.41 mg/dl vs 187.69 mg/dl, p = 0.006, respectively), and LDL-C (110.6 mg/dl vs 96.9 mg/dl, p = 0.004, respectively).

Conclusions: These findings suggest that the R1587K polymorphism of ABCA1 gene was associated with lipid profile of Greek nurses. Women with RK genotype had higher TGs, total and LDL-C concentration compared to RR genotype. These observations may be significant in assessing the risk of CAD since a 1% change in LDL-C is associated with a 1% change of cardiovascular events. Also, TGs concentration were documented to play a significant role in women. However, this needs to be confirmed by larger studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1476-511X-10-56DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3090361PMC
April 2011

In vitro and in vivo effects of statins on platelet-activating factor and its metabolism.

Angiology 2011 Apr 29;62(3):209-18. Epub 2010 Aug 29.

Laboratory of Biochemistry, Faculty of Chemistry, National and Kapodistrian University, Athens, Greece.

Platelet activating factor (PAF) is implicated in cardiovascular disease (CVD). Statins are widely used in these situations. Therefore, we assessed their effect on the biological activities and metabolism of PAF. Several statins, including simvastatin, exhibited an inhibitory effect against PAF, comparable with that of PAF-inhibitors. Simvastatin also suppressed in vivo PAF-biosynthesis via the de novo pathway, in leukocytes of 6 simvastatin-treated volunteers. Total cholesterol and low-density lipoprotein cholesterol were also significantly decreased, whereas high-density lipoprotein cholesterol, triacylglycerol, EC(50), and lag time were unaffected in these participants. Simvastatin with an intact lactone ring also inhibited PAF-activities, while incubation of human mesangial cells with it also resulted in decreased de novo PAF-biosynthesis. This suggests that these simvastatin-dependent effects are independent of its lactone ring. These new actions of statins should be further studied in PAF-implicated pathological conditions such as CVD, cancer, and renal disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0003319710375089DOI Listing
April 2011

Structurally diverse metal coordination compounds, bearing imidodiphosphinate and diphosphinoamine ligands, as potential inhibitors of the platelet activating factor.

Bioinorg Chem Appl 2010 28. Epub 2010 Jun 28.

Biochemistry Laboratory, Faculty of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Zografou, 15771 Athens, Greece.

Metal complexes bearing dichalcogenated imidodiphosphinate [R(2)P(E)NP(E)R(2)'](-) ligands (E = O, S, Se, Te), which act as (E,E) chelates, exhibit a remarkable variety of three-dimensional structures. A series of such complexes, namely, square-planar [Cu{(OPPh(2))(OPPh(2))N-O, O}(2)], tetrahedral [Zn{(EPPh(2))(EPPh(2))N-E,E}(2)], E = O, S, and octahedral [Ga{(OPPh(2))(OPPh(2))N-O,O}(3)], were tested as potential inhibitors of either the platelet activating factor (PAF)- or thrombin-induced aggregation in both washed rabbit platelets and rabbit platelet rich plasma. For comparison, square-planar [Ni{(Ph(2)P)(2)N-S-CHMePh-P, P}X(2)], X = Cl, Br, the corresponding metal salts of all complexes and the (OPPh(2))(OPPh(2))NH ligand were also investigated. Ga(O,O)(3) showed the highest anti-PAF activity but did not inhibit the thrombin-related pathway, whereas Zn(S,S)(2), with also a significant PAF inhibitory effect, exhibited the highest thrombin-related inhibition. Zn(O,O)(2) and Cu(O,O)(2) inhibited moderately both PAF and thrombin, being more effective towards PAF. This work shows that the PAF-inhibitory action depends on the structure of the complexes studied, with the bulkier Ga(O,O)(3) being the most efficient and selective inhibitor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2010/731202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2905917PMC
July 2011

Implication of lipoprotein associated phospholipase A2 activity in oxLDL uptake by macrophages.

J Lipid Res 2010 Aug 23;51(8):2191-201. Epub 2010 Mar 23.

Department of Experimental Physiology, University of Athens Medical School, Athens, Greece.

Recognition and uptake of oxidized LDL (oxLDL) by scavenger receptors of macrophages and foam cell formation are mediated by the oxidatively modified apolipoprotein B (ApoB) and lipid moiety of oxLDL. A great amount of oxidized phosphatidylcholine (oxPC) of oxLDL is hydrolyzed at the sn-2 position by lipoprotein associated phospholipase A(2) (Lp-PLA(2)) to lysophosphatidylcholine and small oxidation products. This study examines the involvement of Lp-PLA(2) in the uptake of oxLDL by mouse peritoneal macrophages. LDL with intact Lp-PLA(2) activity [LDL(+)] and LDL with completely inhibited Lp-PLA(2) activity [LDL(-)] were subjected to oxidation with 5 microM CuSO(4) for 6 h [moderately oxLDL (MoxLDL)], or 24 h [heavily oxLDL (HoxLDL)] and peritoneal macrophages were incubated with these preparations. The uptake of MoxLDL(-) was about 30% increased compared with that of MoxLDL(+), and HoxLDL(-) uptake was about 20% increased compared with that of HoxLDL(+). Inhibition of Lp-PLA(2) activity had no effect on the uptake of ApoB-liposomes conjugates with ApoB isolated from MoxLDL(-), MoxLDL(+), HoxLDL(-), and HoxLDL(+). Liposomes prepared from the lipid extract of MoxLDL(-), MoxLDL(+), HoxLDL(-), and HoxLDL(+) exhibited a similar pattern to that observed in the uptake of the corresponding intact lipoproteins. This study suggests that the progressive inactivation of Lp-PLA(2) during LDL oxidation leads to an increased uptake of oxLDL by macrophages, which could be primarily attributed to the increased uptake of the oxidized phospholipids enriched lipid moiety of oxLDL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1194/jlr.M003558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903815PMC
August 2010

Detection and isolation of antiatherogenic and antioxidant substances present in olive mill wastes by a novel filtration system.

J Agric Food Chem 2009 Nov;57(22):10554-64

Faculty of Chemistry, National and Kapodistrian University of Athens, Athens, Greece.

Olive mill waste water (OMWW) is a major environmental issue in the Mediterranean. We address this problem by investigating the wastes for the presence of biologically active compounds already detected in both olive oil and pomace. Two initial OMWW samples were filtered using two microporous filtering media: (a) clayey diatomite and (b) zeolitic volcanic tuffs, obtaining three filtered samples from each. All initial and filtrated samples were tested for their activity on platelet activating factor (PAF)-induced aggregation. The results showed that the initial samples contain biologically active compounds (PAF inhibitors) and that in their respective last-eluted filtered samples these compounds are purified. These eluted samples, along with their corresponding initial OMWW, were further separated with HPLC and the purified fractions responsible for the aforementioned biological activity, were further studied using chemical determinations and MS analysis. It was confirmed that the PAF inhibitor present in these fractions resembles the one isolated from olive oil. These results offer a new approach on the OMWW handling by offering an alternative use of this waste as starting material for nutritional and/or pharmaceutical purposes in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/jf9016288DOI Listing
November 2009

Acetaminophen-induced liver injury and oxidative stress: protective effect of propofol.

Eur J Anaesthesiol 2009 Jul;26(7):548-53

Second Department of Anesthesiology, Attikon Hospital, National and Kapodistrian University of Athens, Athens, Greece.

Background And Objective: We evaluated the effects of propofol on oxidative stress and acute liver injury and regeneration produced by acetaminophen administration in rats.

Methods: Acetaminophen (3.5 g kg(-1)) was administered by gastric tube to 50 adult male Wistar rats. One minute before acetaminophen, propofol was administered intraperitoneally (60 mg kg(-1)) to 25 rats and diethyl ether to the other 25 animals. All rats were sacrificed. Markers of oxidative stress (malondialdehyde levels, cholesterol/high-density lipoprotein cholesterol fraction and glutathione-S-transferase-pi activity), liver injury (aspartate aminotransferase alanine aminotransferase and alkaline phosphatase and histological signs of inflammation and in-situ apoptosis) and liver regeneration (rate of [3H]thymidine incorporation into hepatic DNA, activity of liver thymidine kinase and mitotic index in hepatocytes) were determined. Unpaired Student's t-test and one-way analysis of variance were used for statistical analysis and a P value of 0.05 or less was considered significant.

Results: All markers of oxidative stress were significantly decreased in propofol-treated animals. Biochemical and histological markers of liver injury and regeneration in propofol-treated animals did not show any significant decrease compared with those observed in the control group.

Conclusion: The antioxidant capacity of propofol, verified in our study, did not manage to prevent liver injury and accelerate regeneration after acetaminophen administration in rats.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/EJA.0b013e32831c8a01DOI Listing
July 2009

Triacylglycerol metabolism.

Curr Drug Targets 2009 Apr;10(4):302-19

Department of Science of Nutrition-Dietetics, Harokopio University, Athens, Greece.

Apart from being the main energy reserves of the human body, triacylglycerols take part in metabolic processes that determine the rate of fatty acid oxidation, the plasma levels of free fatty acids, the biosynthesis of other lipid molecules and the metabolic fate of lipoproteins. Allosteric, hormonal, nutritional and transcriptional signals activate short-term and long-term regulatory mechanisms that assure the storage of triacylglycerols (TAGs) under states of excess energy and their mobilization under conditions of metabolic stress. New enzymes and novel regulatory mechanisms, involved in triacylglycerol metabolism, have been recently discovered and new details on the fine tuning of their metabolic reactions are coming to light. This knowledge will help us understand the biochemical basis of several diseases for the pathogenesis of which triacylglycerols play a role.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/138945009787846443DOI Listing
April 2009

Antibacterial and anti-PAF activity of lipid extracts from sea bass (Dicentrarchus labrax) and gilthead sea bream (Sparus aurata).

Food Chem 2008 Nov 10;111(2):433-8. Epub 2008 Apr 10.

Laboratory of Food Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimioupolis, 157-71 Athens, Greece. Electronic address:

The anti-PAF and the antibacterial activities of lipid extracts obtained from cultured sea bass (Dicentrarchus labrax) and cultured gilthead sea bream (Sparus aurata) were evaluated. Total lipids of sea bass and gilthead sea bream exerted PAF-like activity while, in higher amounts they inhibited this PAF activity. Neutral lipids of both sea bass and gilthead sea bream contained only PAF antagonists while the polar lipid fractions contained both PAF antagonists and agonists. Total lipids of sea bass exhibited stronger PAF-like activity than did those of gilthead sea bream; however, neutral lipids of sea bass contained stronger PAF antagonists than did gilthead sea bream. Total lipids of both sea bass and gilthead sea bream exhibited antibacterial activity only towards Staphylococcus aureus (S. aureus) with those of sea bass being more potent. Subsequently, neutral lipids of both sea bass and gilthead sea bream also showed antibacterial activity against S. aureus and less so towards Escherichia coli (E. coli), while only neutral lipids of sea bass showed antibacterial activity against Enterococcusfaecalis (E. faecalis). Sea bass neutral lipids were more active against S. aureus than were those of gilthead sea bream, while their activity towards E. coli was similar. Polar lipids of both sea bass and gilthead sea bream showed antibacterial activity against all bacteria strains. Sea bass polar lipids were more active towards S. aureus than were those of gilthead sea bream, while their activities against E. faecalis and E. coli were the same. The detected antibacterial activities of the lipid extracts isolated from sea bass and gilthead sea bream were observed in amounts equal to those that exerted either PAF inhibition or PAF-like activity, suggesting that PAF antagonists and agonists of fish lipids may be responsible for the antibacterial activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.foodchem.2008.04.011DOI Listing
November 2008