Alexandra Furtos - Academia.edu (original) (raw)

Papers by Alexandra Furtos

Inorganic Chemistry, 2014

A molecular triangle, based on the self-assembly of 4,7-phenanthroline by a neutral palladium com... more A molecular triangle, based on the self-assembly of 4,7-phenanthroline by a neutral palladium complex, has been synthesized and characterized by a combination of techniques: (1)H NMR and UV-vis absorption spectroscopies, mass spectrometry, elemental analysis, and gel permeation chromatography. This new neutral metallocavitand has demonstrated the capacity to host both anionic and cationic guests, thus acting as an open-shaped heteroditopic receptor. Density functional theory calculations have shown that (i) there is no overtension in the assembly of the discrete triangle, which is more stable than open-chain oligomers, (ii) the adducts formed between the triangle and some salts (modeled in the gas phase) are thermodynamically stable, and (iii) two types of cavities coexist in the triangle, which host ions and ion pairs. This easily accessible triangular unit extends further the rational design of model nanoarchitectures in host-guest chemistry with applications in analytical chemistry and multifunctional molecular materials.

Water Research, 2009

Nonylphenol ethoxylate UV-vis spectroscopy FTIR spectroscopy Mass spectrometry a b s t r a c t A ... more Nonylphenol ethoxylate UV-vis spectroscopy FTIR spectroscopy Mass spectrometry a b s t r a c t A study of inclusion complexation of liquid non-ionic surfactants, nonylphenol (NP) and nonylphenol 9 mole ethoxylate (NP9EO), with b-cyclodextrin (b-CD), was carried out by mass spectrometry, surface tension, and ultraviolet-visible (UV-VIS) and Fourier transform infrared (FTIR) spectroscopies. The inclusion complexation was effectuated by heating at 80 C and filtration of aqueous NP þ b-CD and NP9EO þ b-CD suspensions. The mass spectrometry and surface tension measurements revealed that NP and NP9EO form inclusion complexes with b-CD and b-CD possesses a higher affinity for NP. These results are supported by the data from UV-VIS spectroscopic analyses that have indicated that a three times greater amount of NP is entrapped into b-CD than NP9EO. This phenomenon has been associated with the smaller size and a higher degree of hydrophobicity of NP that favours its entrapment into b-CD as compared to that of NP9EO. At the structural level, the data from FTIR spectroscopic study have indicated that alkyl chains of NP and NP9EO can form van der Waals interactions with the cavity of b-CD.

Journal of Chromatography a, Nov 1, 2009

We describe the development and validation of an on-line solid-phase extraction of large-volume i... more We describe the development and validation of an on-line solid-phase extraction of large-volume injections coupled to liquid chromatography-tandem mass spectrometry method for the simultaneous quantitation and confirmation of 14 selected trace organic contaminants in drinking and surface water. Selected compounds were: anti-infectives (clarithromycin, sulfamethoxazole and trimethoprim), an anticonvulsant (carbamazepine) and its transformation product 10,11-dihydrocarbamazepine, an antihypertensive (enalapril), antineoplastics (cyclophosphamide and methotrexate), herbicides (atrazine, cyanazine, and simazine) and two of their transformation products (deethylatrazine and deisopropylatrazine) and an antiseptic (triclocarban). The breakthrough volume determinations showed that out of all the investigated sorbents, the Strata-X on-line solid-phase extraction column showed the best performance. The method used a load volume of 10.0 mL and was validated using the corresponding matrices, yielding for most compounds, R 2 > 0.99. Extraction recoveries ranged from 60 to 109%. The intra-and inter-day precision were <14 and <16%, respectively. The method detection limits ranged from 0.6 to 6 ng L −1 . Matrix effects were in general low. The performance of the on-line method was demonstrated with the analysis of real water samples. The application of alternative techniques of confirmation was also explored using accurate mass measurements on a time-of-flight mass spectrometer and the data-dependent reverse energy ramp scan on a triple quadrupole.

Analytical Chemistry, Jul 1, 2009

Atmospheric pressure chemical ionization-tandem mass spectrometry (APCI-MS/MS) was applied for th... more Atmospheric pressure chemical ionization-tandem mass spectrometry (APCI-MS/MS) was applied for the first time to the direct analysis of octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5) in gaseous matrixes without extraction or prior chromatographic separation. Mass spectrometric characteristics of both compounds under APCI conditions and their fragmentation behavior in MS/MS were investigated. Unlike the classical gas chromatography/mass spectrometry (GC/MS), which involves solvent extraction before gas chromatography, the proposed approach prevents contamination from GC system components and provides unambiguous structural assignments. The method performs well achieving good linearity (R 2 > 0.997), low limits of detection (4-6 µg/ m 3 ), good precision (RSD < 10%) and accuracy (>93%), and a wide dynamic range. Its applicability to real-world samples was evaluated through measurements of D4 and D5 concentrations in air and biogas samples. The high sensitivity, selectivity, and reliability of this method render our approach a good alternative to the commonly used GC/MS method.

Inorganic Chemistry, 2014

A molecular triangle, based on the self-assembly of 4,7-phenanthroline by a neutral palladium com... more A molecular triangle, based on the self-assembly of 4,7-phenanthroline by a neutral palladium complex, has been synthesized and characterized by a combination of techniques: (1)H NMR and UV-vis absorption spectroscopies, mass spectrometry, elemental analysis, and gel permeation chromatography. This new neutral metallocavitand has demonstrated the capacity to host both anionic and cationic guests, thus acting as an open-shaped heteroditopic receptor. Density functional theory calculations have shown that (i) there is no overtension in the assembly of the discrete triangle, which is more stable than open-chain oligomers, (ii) the adducts formed between the triangle and some salts (modeled in the gas phase) are thermodynamically stable, and (iii) two types of cavities coexist in the triangle, which host ions and ion pairs. This easily accessible triangular unit extends further the rational design of model nanoarchitectures in host-guest chemistry with applications in analytical chemistry and multifunctional molecular materials.

Clinical Science, 2014

Cranberry fruit has been reported to have high antioxidant effectiveness that is potentially link... more Cranberry fruit has been reported to have high antioxidant effectiveness that is potentially linked to its richness in diversified polyphenolic content. The aim of the present study was to determine the role of cranberry polyphenolic fractions in oxidative stress (OxS), inflammation and mitochondrial functions using intestinal Caco-2/15 cells. The combination of HPLC and UltraPerformance LC®-tandem quadrupole (UPLC-TQD) techniques allowed us to characterize the profile of low, medium and high molecular mass polyphenolic compounds in cranberry extracts. The medium molecular mass fraction was enriched with flavonoids and procyanidin dimers whereas procyanidin oligomers (DP &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 4) were the dominant class of polyphenols in the high molecular mass fraction. Pre-incubation of Caco-2/15 cells with these cranberry extracts prevented iron/ascorbate-mediated lipid peroxidation and counteracted lipopolysaccharide-mediated inflammation as evidenced by the decrease in pro-inflammatory cytokines (TNF-α and interleukin-6), cyclo-oxygenase-2 and prostaglandin E2. Cranberry polyphenols (CP) fractions limited both nuclear factor κB activation and Nrf2 down-regulation. Consistently, cranberry procyanidins alleviated OxS-dependent mitochondrial dysfunctions as shown by the rise in ATP production and the up-regulation of Bcl-2, as well as the decline of protein expression of cytochrome c and apoptotic-inducing factor. These mitochondrial effects were associated with a significant stimulation of peroxisome-proliferator-activated receptor γ co-activator-1-α, a central inducing factor of mitochondrial biogenesis and transcriptional co-activator of numerous downstream mediators. Finally, cranberry procyanidins forestalled the effect of iron/ascorbate on the protein expression of mitochondrial transcription factors (mtTFA, mtTFB1, mtTFB2). Our findings provide evidence for the capacity of CP to reduce intestinal OxS and inflammation while improving mitochondrial dysfunction.

PLoS ONE, 2013

Since gastrointestinal mucosa is constantly exposed to reactive oxygen species from various sourc... more Since gastrointestinal mucosa is constantly exposed to reactive oxygen species from various sources, the presence of antioxidants may contribute to the body's natural defenses against inflammatory diseases.

Frontiers in Psychiatry, 2012

Schizophrenia is a complex psychiatric disorder strongly associated with substance use disorders.... more Schizophrenia is a complex psychiatric disorder strongly associated with substance use disorders. Theoretically, schizophrenia and SUD may share endocannabinoid alterations in the brain reward system.The main endocannabinoids, anandamide, and 2-arachidonoylglycerol, are lipids which bind cannabinoid receptors. Oleoylethanolamide (OEA), a fatty-acid ethanolamide, binds peroxisome proliferator-activated receptors.The endocannabinoid system has been shown to be impaired in schizophrenia, and recently, our group has shown that schizophrenia patients with SUD have elevated peripheral levels of anandamide and OEA that do not normalize after 3-month treatment with quetiapine. Objective For comparative purposes, we aimed to measure endocannabinoids in non-psychosis substance abusers and non-abusing schizophrenia patients. Methods Using liquid chromatography and mass spectrometry, we measured plasma levels of anandamide and OEA in nonpsychosis SUD patients, non-abusing schizophrenia patients, and healthy controls. In an open-label manner, all patients received 12-week treatment with quetiapine. Results Anandamide and OEA were reduced in substance abusers without schizophrenia, relative to healthy controls (p < 0.05). Both endocannabinoids were unchanged in non-abusing schizophrenia patients. After quetiapine, anandamide, and OEA levels remained significantly reduced the SUD group (p < 0.05). Discussion Taken together with results of our previous study performed in dual-diagnosis patients, our results suggest that peripheral anandamide and OEA levels are impaired in patients with SUD in opposite ways according to the presence or absence of schizophrenia. Endocannabinoid alterations did not change with treatment, suggesting that they are trait markers. Further studies are necessary to understand the role of endocannabinoids in substance abusers with and without schizophrenia and to examine therapeutic implications.

Water Research, 2009

Nonylphenol ethoxylate UV-vis spectroscopy FTIR spectroscopy Mass spectrometry a b s t r a c t A ... more Nonylphenol ethoxylate UV-vis spectroscopy FTIR spectroscopy Mass spectrometry a b s t r a c t A study of inclusion complexation of liquid non-ionic surfactants, nonylphenol (NP) and nonylphenol 9 mole ethoxylate (NP9EO), with b-cyclodextrin (b-CD), was carried out by mass spectrometry, surface tension, and ultraviolet-visible (UV-VIS) and Fourier transform infrared (FTIR) spectroscopies. The inclusion complexation was effectuated by heating at 80 C and filtration of aqueous NP þ b-CD and NP9EO þ b-CD suspensions. The mass spectrometry and surface tension measurements revealed that NP and NP9EO form inclusion complexes with b-CD and b-CD possesses a higher affinity for NP. These results are supported by the data from UV-VIS spectroscopic analyses that have indicated that a three times greater amount of NP is entrapped into b-CD than NP9EO. This phenomenon has been associated with the smaller size and a higher degree of hydrophobicity of NP that favours its entrapment into b-CD as compared to that of NP9EO. At the structural level, the data from FTIR spectroscopic study have indicated that alkyl chains of NP and NP9EO can form van der Waals interactions with the cavity of b-CD.

Macromolecular Chemistry and Physics, 2013

The synthesis of telechelic poly(ether sulfone)s with methoxy end groups is reported. Molecular w... more The synthesis of telechelic poly(ether sulfone)s with methoxy end groups is reported. Molecular weights ranging from 1600 to 2800 g mol −1 and polydispersities of 1.1-1.2 are synthesized by chain-growth condensation polymerization. The initiator is chosen by using semiempirical calculations and 19 F NMR spectroscopy measurements. The polymers are characterized by NMR spectroscopy and matrix-assisted laser desorption/ionization time of fl ight (MALDI-TOF) mass spectrometry (MS), and are terminated by a methoxy group at one end and a fl uorine at the other, and up to approximately 20% polymer of similar mass but slightly higher polydispersity, methoxy terminated at both ends, is present, along with less than 5% of polymer terminated at both ends by fl uorine atoms. These do not need to be separated, and can be converted to methoxy-ending telechelic blocks, yielding polyvalent, reactive rigid building blocks for copolymer synthesis.

Journal of Macromolecular Science, Part A, 2013

ABSTRACT Syntheses of symmetrical etherketone rigid blocks containing from four to ten aromatic r... more ABSTRACT Syntheses of symmetrical etherketone rigid blocks containing from four to ten aromatic rings were performed by a succession of Williamson synthesis steps, followed by deprotection by BBr3. Solubility decreased upon an increase in number of aromatic rings. Bis-(p-oxy-(p-hydroxyphenyl))benzophenone, a four-ring block, was soluble in the usual solvents (dichloromethane and chloroform), while 6 and 8-ring blocks were only soluble in dichloromethane to which trifluoroacetic acid was added. Rigid-flexible copolyetherketones with very short flexible segments were synthesized by reacting the 8-ring block with dibromo-terminated short alkane chains of 4 to 10 CH2 units in the presence of sodium hydride. Molar masses were estimated by MALDI-TOF, which was also used to verify the incorporation of the flexible spacers in a regular way. Copolymers are of moderate molecular weights (Mw values from 1240 to 2610 g mol−1), and of low polydispersity (from 1.02 to 1.17). Rigid blocks and rigid-flexible copolymers show high crystallinity and low solubility, in spite of the presence of the aliphatic spacers along the chain backbone, showing that incorporation of regularly spaced flexible segments does not decrease crystallization significantly. These flexible chains however decrease thermal stability of the copolymers.

Journal of Controlled Release, 2011

Nanonization is a simple and effective method to improve dissolution rate and oral bioavailabilit... more Nanonization is a simple and effective method to improve dissolution rate and oral bioavailability of drugs with poor water solubility. There is growing interest to downscale the nanocrystal production to enable early preclinical evaluation of new drug candidates when compound availability is scarce. The purpose of the present study was to investigate laser fragmentation to form nanosuspensions in aqueous solution of the insoluble model drug megestrol acetate (MA) using very little quantities of the drug. Laser fragmentation was obtained by focusing a femtosecond (fs) or nanosecond (ns) laser radiation on a magnetically stirred MA suspension in water or aqueous solution of a stabilizing agent. The size distribution and physicochemical properties of the drug nanoparticles were characterized, and the in vitro dissolution and in vivo oral pharmacokinetics of a laser fragmented formulation were evaluated. A MA nanosuspension was also prepared by media milling for comparison purpose. For both laser radiations, smaller particles were obtained as the laser power was increased, but at a cost of higher degradation. Significant nanonization was achieved after a 30-min fs laser treatment at 250 mW and a 1-h ns laser treatment at 2500 mW. The degradation induced by the laser process of the drug was primarily oxidative in nature. The crystal phase of the drug was maintained, although partial loss of crystallinity was observed. The in vitro dissolution rate and in vivo bioavailability of the laser fragmented formulation were similar to those obtained with the nanosuspension prepared by media milling, and significantly improved compared to the coarse drug powder. It follows that this laser nanonization method has potential to be used for the preclinical evaluation of new drug candidates.

Journal of Chromatography A, 2014

A rapid LC-MS/MS method has been developed to simultaneously separate 71 erectile dysfunction (ED... more A rapid LC-MS/MS method has been developed to simultaneously separate 71 erectile dysfunction (ED) drugs and 11 natural ingredients that are sometimes found alongside ED drugs, present in suspected adulterated or counterfeit samples. The separation was achieved in 10min using 2.6μm fused-core C18 particles in a 100×2.1mm column coupled to an LTQ Orbitrap XL mass spectrometer operated in positive electrospray mode. Using a straightforward methanolic extraction procedure, recovery from real samples (tablets, capsules, oral liquids and herbal products) was 92-111% and the lower and upper limits of detection and quantification were in the sub ng/mL and the sub μg/mL ranges, respectively. The intra- and inter-assay precision were ≤3.2% and 10.4% respectively across three concentrations of standards (50, 250 and 1000ng/mL) measured for 4 representative drugs spiked into a tablet-based matrix. This behavior was consistently observed for all the other compounds. The mass accuracy was less than 3ppm. Moreover, an advantage of this method is that the full scan event in the acquisition method associated with the high resolution of the Orbitrap XL allows post-analysis identification, in an untargeted approach, of additional species in the complex matrices. Our LC-MS/MS method for ED drugs was successfully applied to 32 samples and the drug identifications were in 100% agreement with those obtained by the conventional methods HPLC-UV and GC-MS. Following the complete validation of the ED method, it has been introduced in the current counterfeit identification procedures at Health Canada.

Journal of Chromatography A, 2009

We describe the development and validation of an on-line solid-phase extraction of large-volume i... more We describe the development and validation of an on-line solid-phase extraction of large-volume injections coupled to liquid chromatography-tandem mass spectrometry method for the simultaneous quantitation and confirmation of 14 selected trace organic contaminants in drinking and surface water. Selected compounds were: anti-infectives (clarithromycin, sulfamethoxazole and trimethoprim), an anticonvulsant (carbamazepine) and its transformation product 10,11-dihydrocarbamazepine, an antihypertensive (enalapril), antineoplastics (cyclophosphamide and methotrexate), herbicides (atrazine, cyanazine, and simazine) and two of their transformation products (deethylatrazine and deisopropylatrazine) and an antiseptic (triclocarban). The breakthrough volume determinations showed that out of all the investigated sorbents, the Strata-X on-line solid-phase extraction column showed the best performance. The method used a load volume of 10.0 mL and was validated using the corresponding matrices, yielding for most compounds, R 2 > 0.99. Extraction recoveries ranged from 60 to 109%. The intra-and inter-day precision were <14 and <16%, respectively. The method detection limits ranged from 0.6 to 6 ng L −1 . Matrix effects were in general low. The performance of the on-line method was demonstrated with the analysis of real water samples. The application of alternative techniques of confirmation was also explored using accurate mass measurements on a time-of-flight mass spectrometer and the data-dependent reverse energy ramp scan on a triple quadrupole.

Journal of Chromatography A, 2008

In the present study we evaluated two commonly used iodinated contrast agents, iohexol and iodixa... more In the present study we evaluated two commonly used iodinated contrast agents, iohexol and iodixanol, as potential markers of impaired renal function. A reversed phase LC-MS method has been developed in order to separate and quantify the two substances. The assay was linear between 0.02 and 9.7 mol/L for iohexol and between 0.4 and 49.3 mol/L for iodixanol (r 2 > 0.998). The recovery during sample preparation ranged from 89.1 to 112.4%. The intra-and inter-assay RSD values were 3.06-13.6% for iohexol and 4.32-12.7% for iodixanol. The validated method was subsequently applied to 17 patients scheduled for angiographic procedure displaying normal and impaired renal function. A mixture of iohexol and iodixanol was intra-arterially injected and their corresponding plasma levels were determined periodically over a 24 h period following administration. The elimination of both contrast agents followed by the LC-MS approach allowed us to discriminate between patients with normal and impaired renal function at 4, 8 and 24 h after administration. Our preliminary results support the predictive value of iohexol and/or iodixanol clearance in a clinical environment to screen and identify patients at risk of developing CIN.

Journal of Chromatography A, 2009

Chlorogenic acid is the most abundant polyphenol found in the tobacco plant. The biological effec... more Chlorogenic acid is the most abundant polyphenol found in the tobacco plant. The biological effects of its combustion products remain largely unknown. In this study, chlorogenic acid was burned at 640 • C for 2 min and the particulate matter of the smoke was collected onto Cambridge filter pads followed by selective extraction in five different solvents. Various fractions of the chlorogenic acid combustion products were tested for induction of micronuclei in V79 Chinese hamster fibroblast cells. Over 40 compounds were identified in the dimethyl sulfoxide (DMSO) extract by high-performance liquid chromatography coupled to electrospray time-of-flight mass spectrometry (HPLC/TOF-MS). The DMSO extract was then fractionated into three major fractions by preparative LC. The fraction inducing the highest degree of toxicity was further separated into four sub-fractions. The sub-fraction responsible for the most toxic response was determined to contain catechol as its major component. The overall reproducibility of the combustion, the extraction procedure and the chemical characterization of the compounds responsible for the toxicity in the chlorogenic acid smoke were evaluated by LC/TOF-MS.

Journal of Chromatography A, 2008

A novel approach for chitosan oligosaccharide (COS) separation by immobilized metal affinity chro... more A novel approach for chitosan oligosaccharide (COS) separation by immobilized metal affinity chromatography (IMAC) based on the differences in the interactions of chelated copper (II) ions with various COS (dimers, trimers, tetramers) is described. Polyhydroxylic chromatographic supports (agarose CL-6B and silica) were functionalized with various chelating functions such as iminodiacetate (IDA), carboxymethylaspartate (CM-Asp) and tris(carboxymethyl)ethylenediamine (TED). The COS retention capacities of the columns were between 2 and 6 mg/cm 3 , depending on the chelating group. The COS were separated and/or enriched up to 95% for dimer and trimer and 90% for the tetramer, with yields of 60-95%.

Journal of Biological Chemistry, 2002

The presence of intracellular aggregates that contain Cu/Zn superoxide dismutase (SOD1) in spinal... more The presence of intracellular aggregates that contain Cu/Zn superoxide dismutase (SOD1) in spinal cord motor neurons is a pathological hallmark of amyotrophic lateral sclerosis (ALS). Although SOD1 is abundant in all cells, its half-life in motor neurons far exceeds that in any other cell type. On the basis of the premise that the long half-life of the protein increases the potential for oxidative damage, we investigated the effects of oxidation on misfolding/aggregation of SOD1 and ALS-associated SOD1 mutants. Zinc-deficient wild-type SOD1 and SOD1 mutants were extremely prone to form visible aggregates upon oxidation as compared with wild-type holo-protein. Oxidation of select histidine residues that bind metals in the active site mediates SOD1 aggregation. Our results provide a plausible model to explain the accumulation of SOD1 aggregates in motor neurons affected in ALS.

Free Radical Research, 2004

Ceruloplasmin (CP) is a blue copper glycoprotein with multiple physiological functions including ... more Ceruloplasmin (CP) is a blue copper glycoprotein with multiple physiological functions including ferroxidase and oxidase activities. CP is also an important serum oxygen free radical (OFR) scavenger and antioxidant, exerting cardioprotective and antifibrillatory actions. Although it has been reported that CP activities can be inhibited by OFR, the intimate mechanism of this inactivation is still not clear. Exposure of bovine CP to H2O2 induced inactivation of the protein as well as structural alterations as indicated by loss of protein bands by SDS-PAGE. Both phenomena were H2O2 concentration and time dependent. HPLC gel filtration and capillary electrophoresis analysis of CP treated with H2O2 revealed an aggregation of the protein. Quantification of dityrosine formation by fluorescence indicated the involvement of dityrosine bridging, which could be responsible for aggregation of CP under oxidative attack. Oxidative damage to CP under H2O2 treatment was completely prevented by pyruvate, suggesting that the association of CP with antioxidants could extend the range of the protective action of this protein.

Free Radical Biology and Medicine, 2011

Vitamin E, also called tocopherol (TOH), belongs to a class of vitamins referred to as lipid-solu... more Vitamin E, also called tocopherol (TOH), belongs to a class of vitamins referred to as lipid-soluble vitamins and well known for its antioxidant effects in living cells. Vitamin E is not produced in the body; it can only be obtained by mean of food from plant sources or through natural and synthetic supplements. Vitamin E is commercially extracted primarily from vegetable oils such as palm, canola, corn, cotton or soybean oils. Studies have shown that during industrial production a significant loss of tocopherols occurs in the range of 25% to 35% due to either thermal breakdown or chemical reactions. the majority of the tocopherol loss during oil processing is due to oxidation which renders the molecule ineffective with respect to its vitamin's function. Tocopherolquinone is one of the major oxidation products of vitamin E. The present study is the first to demonstrate that stannous chloride (SnCl 2 .2H 2 O) ion is capable of reducing αtocopherolquinone (TQ) back to α-tocopherol. Experiments conducted by reacting pure commercial standard α-TQ with stannous chloride (II) in organic solvent (methanol) yield promising results by reducing 95% of the α-TQ and producing vitamin E. These results led us to the isolation by HPLC of a fraction of TQ that was successfully reduced back to TOH. the TQ was obtained by oxidation reaction in vitro of a small quantity of commercial standard α-TOH and copper chloride (CuCl 2 ). in this study, stannous chloride has also proven to provide an important antioxidation effect by preventing the oxidation of TOH when exposed to a powerful oxidation catalyst such as CuCl 2 . the present study has shown as well for the first time the reaction of chromium (III) hexahydrate CrCl 3 .6 (H 2 O) with αtocopherolquinone resulting in the formation of α-tocopherol. This discovery presents a double advantage with regard to its applications: on one hand it can help reduce significantly the loss of vitamin E during industrial processing and on the other hand it could explain the still unanswered question on the potential antioxidant properties of chromium (III) reported in several publications. Background: It has been shown that dietary supplementation with Malaysian red palm oil improves functional recovery and reduces infarct size, following ischaemia/reperfusion (IR) in rat hearts. We subsequently investigated the composition of several other palm oils. These palm oils are consumed as a regular part of the diet in many parts of Africa and South-America. Materials and Methods: Oils were analyzed for fatty acid composition, antioxidant and trace metal content. Results: Fatty acid and antioxidant composition of palm oils from Africa yielded similar results to that of the Malaysian product. South-American palm oil however showed some differences in fatty acid composition, as well as significant differences in antioxidant content, especially with respect to vitamin E content. Trace metal analysis of oils are under way. Conclusion: Malaysian red palm oil supplementation reduces myocardial ischaemia/reperfusion injury and infarct size, through its natural antioxidant and fatty acid content. We hypothesize that African palm oil will have similar effects than the Malaysian counterpart with regards to cardiovascular protection. Further studies need to be done with the South-American palm oil to determine its effects on cardiovascular protection in the rat model. a (BPA), an important occupational and environmental chemical, causes toxicity to several organ systems including the liver. However, very little is known regarding the precise molecular mechanisms and cellular targets responsible for BPA toxicity. Studies in experimental animal models report that mitochondrial damage could be involved in BPA-induced liver injury. Given that BPA adversely affects the liver, and considering the central role of the liver in whole body energy metabolism and homeostasis, it is critical to understand the mechanisms behind BPA-induced hepatotoxicity. the aim of the present study was to evaluate the effects of BPA on metabolism and mitochondrial function by measuring the oxygen consumption rate (OCR) in primary rat hepatocytes using an XF24 analyzer (Seahorse Bioscience). Primary rat hepatocytes were plated in collagencoated Seahorse 24-well plates, allowed to attach for 5 h, and then exposed to various concentrations of BPA (0, 1,10, and 100 µM) for 12 h before measuring OCR. Basal and maximal respiration, as well as the proton leak, were significantly increased following exposure to 100 µM BPA compared to untreated control hepatocytes. Cell viability was unaffected in rat hepatocytes exposed to 1 µM BPA, and decreased by only 22% and 30% with 10 µM and 100 µM BPA concentrations, respectively. Importantly, these results are in agreement with previous studies showing BPA-mediated increases in the rate of state 4 oxygen consumption in isolated mitochondria. These findings suggest that BPA may cause bioenergetic stress in cells by uncoupling. in summary, our results show that BPA negatively impacts mitochondrial function leading to critical alterations in the metabolic profile of hepatocytes.

Inorganic Chemistry, 2014

A molecular triangle, based on the self-assembly of 4,7-phenanthroline by a neutral palladium com... more A molecular triangle, based on the self-assembly of 4,7-phenanthroline by a neutral palladium complex, has been synthesized and characterized by a combination of techniques: (1)H NMR and UV-vis absorption spectroscopies, mass spectrometry, elemental analysis, and gel permeation chromatography. This new neutral metallocavitand has demonstrated the capacity to host both anionic and cationic guests, thus acting as an open-shaped heteroditopic receptor. Density functional theory calculations have shown that (i) there is no overtension in the assembly of the discrete triangle, which is more stable than open-chain oligomers, (ii) the adducts formed between the triangle and some salts (modeled in the gas phase) are thermodynamically stable, and (iii) two types of cavities coexist in the triangle, which host ions and ion pairs. This easily accessible triangular unit extends further the rational design of model nanoarchitectures in host-guest chemistry with applications in analytical chemistry and multifunctional molecular materials.

Water Research, 2009

Nonylphenol ethoxylate UV-vis spectroscopy FTIR spectroscopy Mass spectrometry a b s t r a c t A ... more Nonylphenol ethoxylate UV-vis spectroscopy FTIR spectroscopy Mass spectrometry a b s t r a c t A study of inclusion complexation of liquid non-ionic surfactants, nonylphenol (NP) and nonylphenol 9 mole ethoxylate (NP9EO), with b-cyclodextrin (b-CD), was carried out by mass spectrometry, surface tension, and ultraviolet-visible (UV-VIS) and Fourier transform infrared (FTIR) spectroscopies. The inclusion complexation was effectuated by heating at 80 C and filtration of aqueous NP þ b-CD and NP9EO þ b-CD suspensions. The mass spectrometry and surface tension measurements revealed that NP and NP9EO form inclusion complexes with b-CD and b-CD possesses a higher affinity for NP. These results are supported by the data from UV-VIS spectroscopic analyses that have indicated that a three times greater amount of NP is entrapped into b-CD than NP9EO. This phenomenon has been associated with the smaller size and a higher degree of hydrophobicity of NP that favours its entrapment into b-CD as compared to that of NP9EO. At the structural level, the data from FTIR spectroscopic study have indicated that alkyl chains of NP and NP9EO can form van der Waals interactions with the cavity of b-CD.

Journal of Chromatography a, Nov 1, 2009

We describe the development and validation of an on-line solid-phase extraction of large-volume i... more We describe the development and validation of an on-line solid-phase extraction of large-volume injections coupled to liquid chromatography-tandem mass spectrometry method for the simultaneous quantitation and confirmation of 14 selected trace organic contaminants in drinking and surface water. Selected compounds were: anti-infectives (clarithromycin, sulfamethoxazole and trimethoprim), an anticonvulsant (carbamazepine) and its transformation product 10,11-dihydrocarbamazepine, an antihypertensive (enalapril), antineoplastics (cyclophosphamide and methotrexate), herbicides (atrazine, cyanazine, and simazine) and two of their transformation products (deethylatrazine and deisopropylatrazine) and an antiseptic (triclocarban). The breakthrough volume determinations showed that out of all the investigated sorbents, the Strata-X on-line solid-phase extraction column showed the best performance. The method used a load volume of 10.0 mL and was validated using the corresponding matrices, yielding for most compounds, R 2 > 0.99. Extraction recoveries ranged from 60 to 109%. The intra-and inter-day precision were <14 and <16%, respectively. The method detection limits ranged from 0.6 to 6 ng L −1 . Matrix effects were in general low. The performance of the on-line method was demonstrated with the analysis of real water samples. The application of alternative techniques of confirmation was also explored using accurate mass measurements on a time-of-flight mass spectrometer and the data-dependent reverse energy ramp scan on a triple quadrupole.

Analytical Chemistry, Jul 1, 2009

Atmospheric pressure chemical ionization-tandem mass spectrometry (APCI-MS/MS) was applied for th... more Atmospheric pressure chemical ionization-tandem mass spectrometry (APCI-MS/MS) was applied for the first time to the direct analysis of octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5) in gaseous matrixes without extraction or prior chromatographic separation. Mass spectrometric characteristics of both compounds under APCI conditions and their fragmentation behavior in MS/MS were investigated. Unlike the classical gas chromatography/mass spectrometry (GC/MS), which involves solvent extraction before gas chromatography, the proposed approach prevents contamination from GC system components and provides unambiguous structural assignments. The method performs well achieving good linearity (R 2 > 0.997), low limits of detection (4-6 µg/ m 3 ), good precision (RSD < 10%) and accuracy (>93%), and a wide dynamic range. Its applicability to real-world samples was evaluated through measurements of D4 and D5 concentrations in air and biogas samples. The high sensitivity, selectivity, and reliability of this method render our approach a good alternative to the commonly used GC/MS method.

Inorganic Chemistry, 2014

A molecular triangle, based on the self-assembly of 4,7-phenanthroline by a neutral palladium com... more A molecular triangle, based on the self-assembly of 4,7-phenanthroline by a neutral palladium complex, has been synthesized and characterized by a combination of techniques: (1)H NMR and UV-vis absorption spectroscopies, mass spectrometry, elemental analysis, and gel permeation chromatography. This new neutral metallocavitand has demonstrated the capacity to host both anionic and cationic guests, thus acting as an open-shaped heteroditopic receptor. Density functional theory calculations have shown that (i) there is no overtension in the assembly of the discrete triangle, which is more stable than open-chain oligomers, (ii) the adducts formed between the triangle and some salts (modeled in the gas phase) are thermodynamically stable, and (iii) two types of cavities coexist in the triangle, which host ions and ion pairs. This easily accessible triangular unit extends further the rational design of model nanoarchitectures in host-guest chemistry with applications in analytical chemistry and multifunctional molecular materials.

Clinical Science, 2014

Cranberry fruit has been reported to have high antioxidant effectiveness that is potentially link... more Cranberry fruit has been reported to have high antioxidant effectiveness that is potentially linked to its richness in diversified polyphenolic content. The aim of the present study was to determine the role of cranberry polyphenolic fractions in oxidative stress (OxS), inflammation and mitochondrial functions using intestinal Caco-2/15 cells. The combination of HPLC and UltraPerformance LC®-tandem quadrupole (UPLC-TQD) techniques allowed us to characterize the profile of low, medium and high molecular mass polyphenolic compounds in cranberry extracts. The medium molecular mass fraction was enriched with flavonoids and procyanidin dimers whereas procyanidin oligomers (DP &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 4) were the dominant class of polyphenols in the high molecular mass fraction. Pre-incubation of Caco-2/15 cells with these cranberry extracts prevented iron/ascorbate-mediated lipid peroxidation and counteracted lipopolysaccharide-mediated inflammation as evidenced by the decrease in pro-inflammatory cytokines (TNF-α and interleukin-6), cyclo-oxygenase-2 and prostaglandin E2. Cranberry polyphenols (CP) fractions limited both nuclear factor κB activation and Nrf2 down-regulation. Consistently, cranberry procyanidins alleviated OxS-dependent mitochondrial dysfunctions as shown by the rise in ATP production and the up-regulation of Bcl-2, as well as the decline of protein expression of cytochrome c and apoptotic-inducing factor. These mitochondrial effects were associated with a significant stimulation of peroxisome-proliferator-activated receptor γ co-activator-1-α, a central inducing factor of mitochondrial biogenesis and transcriptional co-activator of numerous downstream mediators. Finally, cranberry procyanidins forestalled the effect of iron/ascorbate on the protein expression of mitochondrial transcription factors (mtTFA, mtTFB1, mtTFB2). Our findings provide evidence for the capacity of CP to reduce intestinal OxS and inflammation while improving mitochondrial dysfunction.

PLoS ONE, 2013

Since gastrointestinal mucosa is constantly exposed to reactive oxygen species from various sourc... more Since gastrointestinal mucosa is constantly exposed to reactive oxygen species from various sources, the presence of antioxidants may contribute to the body's natural defenses against inflammatory diseases.

Frontiers in Psychiatry, 2012

Schizophrenia is a complex psychiatric disorder strongly associated with substance use disorders.... more Schizophrenia is a complex psychiatric disorder strongly associated with substance use disorders. Theoretically, schizophrenia and SUD may share endocannabinoid alterations in the brain reward system.The main endocannabinoids, anandamide, and 2-arachidonoylglycerol, are lipids which bind cannabinoid receptors. Oleoylethanolamide (OEA), a fatty-acid ethanolamide, binds peroxisome proliferator-activated receptors.The endocannabinoid system has been shown to be impaired in schizophrenia, and recently, our group has shown that schizophrenia patients with SUD have elevated peripheral levels of anandamide and OEA that do not normalize after 3-month treatment with quetiapine. Objective For comparative purposes, we aimed to measure endocannabinoids in non-psychosis substance abusers and non-abusing schizophrenia patients. Methods Using liquid chromatography and mass spectrometry, we measured plasma levels of anandamide and OEA in nonpsychosis SUD patients, non-abusing schizophrenia patients, and healthy controls. In an open-label manner, all patients received 12-week treatment with quetiapine. Results Anandamide and OEA were reduced in substance abusers without schizophrenia, relative to healthy controls (p < 0.05). Both endocannabinoids were unchanged in non-abusing schizophrenia patients. After quetiapine, anandamide, and OEA levels remained significantly reduced the SUD group (p < 0.05). Discussion Taken together with results of our previous study performed in dual-diagnosis patients, our results suggest that peripheral anandamide and OEA levels are impaired in patients with SUD in opposite ways according to the presence or absence of schizophrenia. Endocannabinoid alterations did not change with treatment, suggesting that they are trait markers. Further studies are necessary to understand the role of endocannabinoids in substance abusers with and without schizophrenia and to examine therapeutic implications.

Water Research, 2009

Nonylphenol ethoxylate UV-vis spectroscopy FTIR spectroscopy Mass spectrometry a b s t r a c t A ... more Nonylphenol ethoxylate UV-vis spectroscopy FTIR spectroscopy Mass spectrometry a b s t r a c t A study of inclusion complexation of liquid non-ionic surfactants, nonylphenol (NP) and nonylphenol 9 mole ethoxylate (NP9EO), with b-cyclodextrin (b-CD), was carried out by mass spectrometry, surface tension, and ultraviolet-visible (UV-VIS) and Fourier transform infrared (FTIR) spectroscopies. The inclusion complexation was effectuated by heating at 80 C and filtration of aqueous NP þ b-CD and NP9EO þ b-CD suspensions. The mass spectrometry and surface tension measurements revealed that NP and NP9EO form inclusion complexes with b-CD and b-CD possesses a higher affinity for NP. These results are supported by the data from UV-VIS spectroscopic analyses that have indicated that a three times greater amount of NP is entrapped into b-CD than NP9EO. This phenomenon has been associated with the smaller size and a higher degree of hydrophobicity of NP that favours its entrapment into b-CD as compared to that of NP9EO. At the structural level, the data from FTIR spectroscopic study have indicated that alkyl chains of NP and NP9EO can form van der Waals interactions with the cavity of b-CD.

Macromolecular Chemistry and Physics, 2013

The synthesis of telechelic poly(ether sulfone)s with methoxy end groups is reported. Molecular w... more The synthesis of telechelic poly(ether sulfone)s with methoxy end groups is reported. Molecular weights ranging from 1600 to 2800 g mol −1 and polydispersities of 1.1-1.2 are synthesized by chain-growth condensation polymerization. The initiator is chosen by using semiempirical calculations and 19 F NMR spectroscopy measurements. The polymers are characterized by NMR spectroscopy and matrix-assisted laser desorption/ionization time of fl ight (MALDI-TOF) mass spectrometry (MS), and are terminated by a methoxy group at one end and a fl uorine at the other, and up to approximately 20% polymer of similar mass but slightly higher polydispersity, methoxy terminated at both ends, is present, along with less than 5% of polymer terminated at both ends by fl uorine atoms. These do not need to be separated, and can be converted to methoxy-ending telechelic blocks, yielding polyvalent, reactive rigid building blocks for copolymer synthesis.

Journal of Macromolecular Science, Part A, 2013

ABSTRACT Syntheses of symmetrical etherketone rigid blocks containing from four to ten aromatic r... more ABSTRACT Syntheses of symmetrical etherketone rigid blocks containing from four to ten aromatic rings were performed by a succession of Williamson synthesis steps, followed by deprotection by BBr3. Solubility decreased upon an increase in number of aromatic rings. Bis-(p-oxy-(p-hydroxyphenyl))benzophenone, a four-ring block, was soluble in the usual solvents (dichloromethane and chloroform), while 6 and 8-ring blocks were only soluble in dichloromethane to which trifluoroacetic acid was added. Rigid-flexible copolyetherketones with very short flexible segments were synthesized by reacting the 8-ring block with dibromo-terminated short alkane chains of 4 to 10 CH2 units in the presence of sodium hydride. Molar masses were estimated by MALDI-TOF, which was also used to verify the incorporation of the flexible spacers in a regular way. Copolymers are of moderate molecular weights (Mw values from 1240 to 2610 g mol−1), and of low polydispersity (from 1.02 to 1.17). Rigid blocks and rigid-flexible copolymers show high crystallinity and low solubility, in spite of the presence of the aliphatic spacers along the chain backbone, showing that incorporation of regularly spaced flexible segments does not decrease crystallization significantly. These flexible chains however decrease thermal stability of the copolymers.

Journal of Controlled Release, 2011

Nanonization is a simple and effective method to improve dissolution rate and oral bioavailabilit... more Nanonization is a simple and effective method to improve dissolution rate and oral bioavailability of drugs with poor water solubility. There is growing interest to downscale the nanocrystal production to enable early preclinical evaluation of new drug candidates when compound availability is scarce. The purpose of the present study was to investigate laser fragmentation to form nanosuspensions in aqueous solution of the insoluble model drug megestrol acetate (MA) using very little quantities of the drug. Laser fragmentation was obtained by focusing a femtosecond (fs) or nanosecond (ns) laser radiation on a magnetically stirred MA suspension in water or aqueous solution of a stabilizing agent. The size distribution and physicochemical properties of the drug nanoparticles were characterized, and the in vitro dissolution and in vivo oral pharmacokinetics of a laser fragmented formulation were evaluated. A MA nanosuspension was also prepared by media milling for comparison purpose. For both laser radiations, smaller particles were obtained as the laser power was increased, but at a cost of higher degradation. Significant nanonization was achieved after a 30-min fs laser treatment at 250 mW and a 1-h ns laser treatment at 2500 mW. The degradation induced by the laser process of the drug was primarily oxidative in nature. The crystal phase of the drug was maintained, although partial loss of crystallinity was observed. The in vitro dissolution rate and in vivo bioavailability of the laser fragmented formulation were similar to those obtained with the nanosuspension prepared by media milling, and significantly improved compared to the coarse drug powder. It follows that this laser nanonization method has potential to be used for the preclinical evaluation of new drug candidates.

Journal of Chromatography A, 2014

A rapid LC-MS/MS method has been developed to simultaneously separate 71 erectile dysfunction (ED... more A rapid LC-MS/MS method has been developed to simultaneously separate 71 erectile dysfunction (ED) drugs and 11 natural ingredients that are sometimes found alongside ED drugs, present in suspected adulterated or counterfeit samples. The separation was achieved in 10min using 2.6μm fused-core C18 particles in a 100×2.1mm column coupled to an LTQ Orbitrap XL mass spectrometer operated in positive electrospray mode. Using a straightforward methanolic extraction procedure, recovery from real samples (tablets, capsules, oral liquids and herbal products) was 92-111% and the lower and upper limits of detection and quantification were in the sub ng/mL and the sub μg/mL ranges, respectively. The intra- and inter-assay precision were ≤3.2% and 10.4% respectively across three concentrations of standards (50, 250 and 1000ng/mL) measured for 4 representative drugs spiked into a tablet-based matrix. This behavior was consistently observed for all the other compounds. The mass accuracy was less than 3ppm. Moreover, an advantage of this method is that the full scan event in the acquisition method associated with the high resolution of the Orbitrap XL allows post-analysis identification, in an untargeted approach, of additional species in the complex matrices. Our LC-MS/MS method for ED drugs was successfully applied to 32 samples and the drug identifications were in 100% agreement with those obtained by the conventional methods HPLC-UV and GC-MS. Following the complete validation of the ED method, it has been introduced in the current counterfeit identification procedures at Health Canada.

Journal of Chromatography A, 2009

We describe the development and validation of an on-line solid-phase extraction of large-volume i... more We describe the development and validation of an on-line solid-phase extraction of large-volume injections coupled to liquid chromatography-tandem mass spectrometry method for the simultaneous quantitation and confirmation of 14 selected trace organic contaminants in drinking and surface water. Selected compounds were: anti-infectives (clarithromycin, sulfamethoxazole and trimethoprim), an anticonvulsant (carbamazepine) and its transformation product 10,11-dihydrocarbamazepine, an antihypertensive (enalapril), antineoplastics (cyclophosphamide and methotrexate), herbicides (atrazine, cyanazine, and simazine) and two of their transformation products (deethylatrazine and deisopropylatrazine) and an antiseptic (triclocarban). The breakthrough volume determinations showed that out of all the investigated sorbents, the Strata-X on-line solid-phase extraction column showed the best performance. The method used a load volume of 10.0 mL and was validated using the corresponding matrices, yielding for most compounds, R 2 > 0.99. Extraction recoveries ranged from 60 to 109%. The intra-and inter-day precision were <14 and <16%, respectively. The method detection limits ranged from 0.6 to 6 ng L −1 . Matrix effects were in general low. The performance of the on-line method was demonstrated with the analysis of real water samples. The application of alternative techniques of confirmation was also explored using accurate mass measurements on a time-of-flight mass spectrometer and the data-dependent reverse energy ramp scan on a triple quadrupole.

Journal of Chromatography A, 2008

In the present study we evaluated two commonly used iodinated contrast agents, iohexol and iodixa... more In the present study we evaluated two commonly used iodinated contrast agents, iohexol and iodixanol, as potential markers of impaired renal function. A reversed phase LC-MS method has been developed in order to separate and quantify the two substances. The assay was linear between 0.02 and 9.7 mol/L for iohexol and between 0.4 and 49.3 mol/L for iodixanol (r 2 > 0.998). The recovery during sample preparation ranged from 89.1 to 112.4%. The intra-and inter-assay RSD values were 3.06-13.6% for iohexol and 4.32-12.7% for iodixanol. The validated method was subsequently applied to 17 patients scheduled for angiographic procedure displaying normal and impaired renal function. A mixture of iohexol and iodixanol was intra-arterially injected and their corresponding plasma levels were determined periodically over a 24 h period following administration. The elimination of both contrast agents followed by the LC-MS approach allowed us to discriminate between patients with normal and impaired renal function at 4, 8 and 24 h after administration. Our preliminary results support the predictive value of iohexol and/or iodixanol clearance in a clinical environment to screen and identify patients at risk of developing CIN.

Journal of Chromatography A, 2009

Chlorogenic acid is the most abundant polyphenol found in the tobacco plant. The biological effec... more Chlorogenic acid is the most abundant polyphenol found in the tobacco plant. The biological effects of its combustion products remain largely unknown. In this study, chlorogenic acid was burned at 640 • C for 2 min and the particulate matter of the smoke was collected onto Cambridge filter pads followed by selective extraction in five different solvents. Various fractions of the chlorogenic acid combustion products were tested for induction of micronuclei in V79 Chinese hamster fibroblast cells. Over 40 compounds were identified in the dimethyl sulfoxide (DMSO) extract by high-performance liquid chromatography coupled to electrospray time-of-flight mass spectrometry (HPLC/TOF-MS). The DMSO extract was then fractionated into three major fractions by preparative LC. The fraction inducing the highest degree of toxicity was further separated into four sub-fractions. The sub-fraction responsible for the most toxic response was determined to contain catechol as its major component. The overall reproducibility of the combustion, the extraction procedure and the chemical characterization of the compounds responsible for the toxicity in the chlorogenic acid smoke were evaluated by LC/TOF-MS.

Journal of Chromatography A, 2008

A novel approach for chitosan oligosaccharide (COS) separation by immobilized metal affinity chro... more A novel approach for chitosan oligosaccharide (COS) separation by immobilized metal affinity chromatography (IMAC) based on the differences in the interactions of chelated copper (II) ions with various COS (dimers, trimers, tetramers) is described. Polyhydroxylic chromatographic supports (agarose CL-6B and silica) were functionalized with various chelating functions such as iminodiacetate (IDA), carboxymethylaspartate (CM-Asp) and tris(carboxymethyl)ethylenediamine (TED). The COS retention capacities of the columns were between 2 and 6 mg/cm 3 , depending on the chelating group. The COS were separated and/or enriched up to 95% for dimer and trimer and 90% for the tetramer, with yields of 60-95%.

Journal of Biological Chemistry, 2002

The presence of intracellular aggregates that contain Cu/Zn superoxide dismutase (SOD1) in spinal... more The presence of intracellular aggregates that contain Cu/Zn superoxide dismutase (SOD1) in spinal cord motor neurons is a pathological hallmark of amyotrophic lateral sclerosis (ALS). Although SOD1 is abundant in all cells, its half-life in motor neurons far exceeds that in any other cell type. On the basis of the premise that the long half-life of the protein increases the potential for oxidative damage, we investigated the effects of oxidation on misfolding/aggregation of SOD1 and ALS-associated SOD1 mutants. Zinc-deficient wild-type SOD1 and SOD1 mutants were extremely prone to form visible aggregates upon oxidation as compared with wild-type holo-protein. Oxidation of select histidine residues that bind metals in the active site mediates SOD1 aggregation. Our results provide a plausible model to explain the accumulation of SOD1 aggregates in motor neurons affected in ALS.

Free Radical Research, 2004

Ceruloplasmin (CP) is a blue copper glycoprotein with multiple physiological functions including ... more Ceruloplasmin (CP) is a blue copper glycoprotein with multiple physiological functions including ferroxidase and oxidase activities. CP is also an important serum oxygen free radical (OFR) scavenger and antioxidant, exerting cardioprotective and antifibrillatory actions. Although it has been reported that CP activities can be inhibited by OFR, the intimate mechanism of this inactivation is still not clear. Exposure of bovine CP to H2O2 induced inactivation of the protein as well as structural alterations as indicated by loss of protein bands by SDS-PAGE. Both phenomena were H2O2 concentration and time dependent. HPLC gel filtration and capillary electrophoresis analysis of CP treated with H2O2 revealed an aggregation of the protein. Quantification of dityrosine formation by fluorescence indicated the involvement of dityrosine bridging, which could be responsible for aggregation of CP under oxidative attack. Oxidative damage to CP under H2O2 treatment was completely prevented by pyruvate, suggesting that the association of CP with antioxidants could extend the range of the protective action of this protein.

Free Radical Biology and Medicine, 2011

Vitamin E, also called tocopherol (TOH), belongs to a class of vitamins referred to as lipid-solu... more Vitamin E, also called tocopherol (TOH), belongs to a class of vitamins referred to as lipid-soluble vitamins and well known for its antioxidant effects in living cells. Vitamin E is not produced in the body; it can only be obtained by mean of food from plant sources or through natural and synthetic supplements. Vitamin E is commercially extracted primarily from vegetable oils such as palm, canola, corn, cotton or soybean oils. Studies have shown that during industrial production a significant loss of tocopherols occurs in the range of 25% to 35% due to either thermal breakdown or chemical reactions. the majority of the tocopherol loss during oil processing is due to oxidation which renders the molecule ineffective with respect to its vitamin's function. Tocopherolquinone is one of the major oxidation products of vitamin E. The present study is the first to demonstrate that stannous chloride (SnCl 2 .2H 2 O) ion is capable of reducing αtocopherolquinone (TQ) back to α-tocopherol. Experiments conducted by reacting pure commercial standard α-TQ with stannous chloride (II) in organic solvent (methanol) yield promising results by reducing 95% of the α-TQ and producing vitamin E. These results led us to the isolation by HPLC of a fraction of TQ that was successfully reduced back to TOH. the TQ was obtained by oxidation reaction in vitro of a small quantity of commercial standard α-TOH and copper chloride (CuCl 2 ). in this study, stannous chloride has also proven to provide an important antioxidation effect by preventing the oxidation of TOH when exposed to a powerful oxidation catalyst such as CuCl 2 . the present study has shown as well for the first time the reaction of chromium (III) hexahydrate CrCl 3 .6 (H 2 O) with αtocopherolquinone resulting in the formation of α-tocopherol. This discovery presents a double advantage with regard to its applications: on one hand it can help reduce significantly the loss of vitamin E during industrial processing and on the other hand it could explain the still unanswered question on the potential antioxidant properties of chromium (III) reported in several publications. Background: It has been shown that dietary supplementation with Malaysian red palm oil improves functional recovery and reduces infarct size, following ischaemia/reperfusion (IR) in rat hearts. We subsequently investigated the composition of several other palm oils. These palm oils are consumed as a regular part of the diet in many parts of Africa and South-America. Materials and Methods: Oils were analyzed for fatty acid composition, antioxidant and trace metal content. Results: Fatty acid and antioxidant composition of palm oils from Africa yielded similar results to that of the Malaysian product. South-American palm oil however showed some differences in fatty acid composition, as well as significant differences in antioxidant content, especially with respect to vitamin E content. Trace metal analysis of oils are under way. Conclusion: Malaysian red palm oil supplementation reduces myocardial ischaemia/reperfusion injury and infarct size, through its natural antioxidant and fatty acid content. We hypothesize that African palm oil will have similar effects than the Malaysian counterpart with regards to cardiovascular protection. Further studies need to be done with the South-American palm oil to determine its effects on cardiovascular protection in the rat model. a (BPA), an important occupational and environmental chemical, causes toxicity to several organ systems including the liver. However, very little is known regarding the precise molecular mechanisms and cellular targets responsible for BPA toxicity. Studies in experimental animal models report that mitochondrial damage could be involved in BPA-induced liver injury. Given that BPA adversely affects the liver, and considering the central role of the liver in whole body energy metabolism and homeostasis, it is critical to understand the mechanisms behind BPA-induced hepatotoxicity. the aim of the present study was to evaluate the effects of BPA on metabolism and mitochondrial function by measuring the oxygen consumption rate (OCR) in primary rat hepatocytes using an XF24 analyzer (Seahorse Bioscience). Primary rat hepatocytes were plated in collagencoated Seahorse 24-well plates, allowed to attach for 5 h, and then exposed to various concentrations of BPA (0, 1,10, and 100 µM) for 12 h before measuring OCR. Basal and maximal respiration, as well as the proton leak, were significantly increased following exposure to 100 µM BPA compared to untreated control hepatocytes. Cell viability was unaffected in rat hepatocytes exposed to 1 µM BPA, and decreased by only 22% and 30% with 10 µM and 100 µM BPA concentrations, respectively. Importantly, these results are in agreement with previous studies showing BPA-mediated increases in the rate of state 4 oxygen consumption in isolated mitochondria. These findings suggest that BPA may cause bioenergetic stress in cells by uncoupling. in summary, our results show that BPA negatively impacts mitochondrial function leading to critical alterations in the metabolic profile of hepatocytes.