A soybean-based diet modulates cadmium-induced vascular apoptosis.

Cadmium (Cd) exposure has been associated with an increased risk of cardiovascular diseases. The diet is a modifiable source of protecting or damaging factors that may affect this risk. Herein we tested the hypothesis that a soybean-based diet (SBD) protects the vascular wall of the aorta against Cd-induced pro-inflammatory and pro-apoptotic effects. To test this hypothesis, we fed male Wistar rats for 60 days with a casein-based diet (CBD) or an SBD. These animals were also exposed to tap-water without (CBD-Co/SBD-Co) or with 15(CBD-15Cd/SBD-15Cd) or 100 (CBD-100Cd/SBD-100Cd) ppm of Cd. Inflammatory parameters (mRNAs and/or proteins) were measured in thoracic aorta tissue. These included inducible and endothelial nitric oxide synthases, cyclooxygenase-2, intracellular-adhesion molecule-1, and vascular cell-adhesion molecule-1. As pro-apoptotic parameters, we measured Bax and Bcl-2 mRNA/protein, as well as TUNEL positive cells in the aorta tissue. Compared to CBD-Co, inflammatory and apoptosis markers increased in the aorta with the concentration of Cd in the drinking water. These effects were not observed in either SBD-15Cd or SBD-100Cd, which were similar to CBD-Co. Cd content in serum and in aortas from animals fed CBD-Co/SBD-15Cd or CBD-Co/SBD-100Cd were similar suggesting that, if any, the effect of SBD is not due to changes in Cd bioaccumulation, but due to secondary effects linked to the composition of the dietary soybean flour. Our findings are consistent with a protective effect of an SBD against Cd-induced inflammation and apoptosis in the thoracic aorta in a rat model.

Quantitative structure-activity relationship to elucidate human CYP2A6 inhibition by organosulfur compounds.

CYP2A6 is a human enzyme responsible for the metabolic elimination of nicotine, and it is also involved in the activation of procarcinogenic nitrosamines, especially those present in tobacco smoke. Several investigations have reported that reducing this enzyme activity may contribute to anti-smoking therapy as well as reducing the risk of promutagens in the body. For these reasons, several authors investigate selective inhibitors molecules toward this enzyme. The aim of this study was to evaluate the interactions between a set of organosulfur compounds and the CYP2A6 enzyme by a quantitative structure-activity relationship (QSAR) analysis. The present work provides a better understanding of the mechanisms involved, with the final goal of providing information for the future design of CYP2A6 inhibitors based on dietary compounds. The reported activity data were modeled by means of multiple regression analysis (MLR) and partial least-squares (PLS) techniques. The results indicate that hydrophobic and steric factors govern the union, while electronic factors are strongly involved in the case of monosulfides.

Determining the geographical origin of Sechium edule fruits by multielement analysis and advanced chemometric techniques.

This paper describes the determination and evaluation of the major and trace element composition (Al, As, Ba, Ca, Cd, Co, Cu, Fe, K, Mg, Mn, Na, Pb, Sr and Zn) of Sechium edule (Jacq) Swartz fruits collected from four different places of production in Corrientes province, Argentina. Element concentrations were determined by using inductively coupled plasma optical emission spectrometry (ICP OES) after microwave digestion. The accuracy was confirmed with standard reference material of spinach leaves (NIST, 1570a) and spiking tests. Principal component analysis (PCA), linear discriminant analysis (LDA), k-nearest neighbors (kNN), partial least square-discriminant analysis (PLS-DA) and support vector machine (SVM) were applied to the results for discriminating the geographical origin of S. edule fruits. Finally, the LDA method was found to perform best with up to 90% accuracy rate based on the following elements: Ca, Ba, Cu, Mn, Na, Sr, and Zn.

Molecular factors influencing the affinity of flavonoid compounds on P-glycoprotein efflux transporter.

The most common mechanism of the so-called multidrug resistance (MDR), is mainly associated with an over expression of P-glycoprotein (Pgp). It is an ATP-dependent transport protein that limits the intracellular accumulation of a variety of structurally unrelated compounds within various organs and normal tissues such as kidney, small intestine and the blood brain barrier. Thus, the expression of Pgp has a major impact on the pharmacokinetic profile of many therapeutic agents and therefore, overcoming Pgp-mediated efflux constitutes an attractive means of potentially enhancing their therapeutic efficacy. The flavonoids comprise a large group of polyphenolic compounds that occur in plants and vegetables, and they have been shown to display a wide variety of biological activities. For example, anti-inflammatory, antioxidant, antiallergic, hepatoprotective, antithrombotic, antiviral, and anticarcinogenic activities. The interactions between flavonoids and Pgp have also been extensively studied and some quantitative structure-activity relationships (QSAR) have been reported. In the present work, we have employed 2D-QSAR analysis to evaluate the interactions between Pgp and several flavonoid compounds with the aim of identifying the molecular factors responsible for the Pgp-binding affinity evidenced by these compounds. Thus, the reported data for dissociation constants (KD) between Pgp and 62 flavonoid compounds were modeled by means of multiple regression analysis (MLR), and structures of the compounds under study were characterized by means of calculated physicochemical properties and several topological and constitutional descriptors, as well as geometrical and quantum chemical indexes. The obtained results suggest that the hydrophobic and especially geometric factors are of prime importance for binding, whereas in the case of flavonoid derivatives with flavone (flavonols), flavanone and isoflavone nuclei, the electronic factors are also involved in electron donor/acceptor interactions. In addition, in the case of chalcones, the results suggest that the affinity toward P-gp of such compounds is mainly governed by intermolecular dispersive interactions at the binding site.

Multivariate characterization of argentinean mistletoe,Ligaria cuneifolia (Loranthaceae) according to theirmineral nutrient composition / Caracterización multivariable de muérdago criollo, Ligaria cuneifolia (Loranthaceae) de acuerdo a su composición mineral

The aim of this study was to characterize samples of Ligaria cuneifolia collected from three areas of the north-east region of Argentina, during two sampling periods. In this work, the authors propose a mathematical model for searching associations among mineral contents and other factors such us geographic origin or sampling period. Mineral monitoring as a pattern recognition method is a promising tool in the characterization and/or standardization of phytomedicines. In the present work measurable amounts of Al, Ca, Co, Cr, Cu, Fe, K, Li, Mg, Mn, Na, P, Sr, and Zn were detected in phytopharmaceutical samples of L. cuneifolia by inductively coupled plasma optical emission spectrometry (ICP-OES). Finally, this methodology allows reliable determinations of mineral content in pharmaceutical quality control of medicinal plants.

El objetivo de este estudio fue caracterizar muestras de Ligaria cuneifolia recolectadas en tres zonas de la región noreste de Argentina, durante dos períodos de muestreo. En este trabajo los autores proponen un modelo matemático para la búsqueda de asociaciones entre el contenido mineral y otros factores como el origen geográfico o el periodo de muestreo. El monitoreo de las concentraciones de los elementos minerales, como método para el reconocimiento de patrones, es una herramienta prometedora en la caracterización y/o estandarización de fitofármacos. En el presente trabajo se pudieron detectar cantidades medibles de Al, Ca, Co, Cr, Cu, Fe, K, Li, Mg, Mn, Na, P, Sr y Zn que fueron detectadas en muestras fitomedicinales de L. cuneifolia por espectroscopía de emisión óptica de plasma acoplado inductivamente (ICP-OES). Finalmente, esta metodología permitió realizar determinaciones confiables del contenido mineral en el control de calidad farmacéutica de plantas medicinales.

Evaluation of macro and microminerals in crude drugs and infusions of five herbs widely used as sedatives

It has been determined the concentration of fourteen micro and macrominerals (Al, Ca, Co, Cr, Cu, Fe, K, Li, Mg, Mn, Na, P, Se, and Zn) in both crude drugs and infusions of Melissa officinalis L., Lamiaceae, Nepeta cataria L., Lamiaceae, Passiflora caerulea L., Passifloraceae, Tilia x moltkei Späth ex C.K. Schneid., Tiliaceae, and Valeriana officinalis L., Caprifoliaceae. These herbs are widely consumed by its sedative properties, either alone or in herb mixtures. All measurements were performed using an inductively coupled plasma optical emission spectrometer (ICP-OES). The products were obtained from regional markets, mainly in San Luis province (Argentina). The estimated daily intake was compared with current recommendations. All products and its infusions were included within the upper tolerable limits for minerals, in trace elements such as toxic elements present at low levels.

Multielemental analysis and classification of amaranth seeds according to their botanical origin.

The characterization of amaranth seeds (Amaranthus spp.) was developed for Amaranthus hypochondriacus, Amaranthus cruentus, and Amaranthus dubius. The elemental concentrations were determined by inductively coupled plasma optic atomic spectroscopy. Pattern recognition methods were used for the characterization of seed samples: nonsupervised methods included principal components analysis and cluster analysis; supervised methods were linear discriminant analysis and partial least squares discriminant analysis (PLS-DA). Informed are the concentrations of the following elements: Ag, Al, Ba, Ca, Co, Cr, Cu, Fe, K, La, Li, Mg, Mn, Mo, Na, Ni, P, S, Sr, V, Zn, and Zr. The lowest mineral content was found in A. hypochondriacus, and the highest one was found in A. dubius. For the classification, selected variables for all multivariate methods were Ba, Cr, Li, Mn, Ni, S, and Sr. Nonsupervised methods allowed us to distinguish between the three species of amaranth; however, PLS-DA supervised methods showed the best prediction ability.

Simultaneous determination of amoxicillin and diclofenac in pharmaceutical formulations using UV spectral data and the PLS chemometric method.

A new method for the simultaneous determination of amoxicillin trihydrate (AMT) and sodium diclofenac (DIC) in pharmaceutical formulations is proposed. The resolution of binary mixtures of these drugs has been accomplished by using partial least squares (PLS) regression analysis. The model was obtained from UV spectral data and validated by internal cross-validation; it was used to find the concentration of analytes in some commercial samples. The method was applied in the concentration ranges of 0-120.0 mg L(-1) for AMT and 0-16.0 mg L(-1) for DIC, allowing a rapid, accurate and precise simultaneous estimation of the concentration of both analytes of interest in the presence of small amounts of different, unmodelled, absorbing excipients, in spite of their important spectral overlapping. The accuracy, precision and figures of merit (FOM) for AMT and DIC were calculated. This new method proved to be useful for a fast and simultaneous determination of AMT and DIC in pharmaceutical formulations.

Characterisation of two South American food and medicinal plants by chemometric methods based on their multielemental composition.

INTRODUCTION: The chemometric characterisation of two plants frequently used as food and medicinal species, Achyrocline satureioides and Achyrocline venosa (Asteraceae: Gnaphalieae), was carried out based on their mineral composition. Both species, known by the common name of 'marcelas', are very similar in their morphological features but they have different medicinal and food properties. OBJECTIVE: To develop multivariate models for the classification of A. satureiodes and A. venosa based on their mineral content. METHODOLOGY: The analytic determinations were made by means of inductively coupled plasma optical emission spectrometry from aerial parts of the plants. An internal standard was used to evaluate the accuracy in the sample treatment and the recovery of toxic elements was studied. The multivariate methods used include principal components analysis, cluster analysis and linear discriminant analysis. RESULTS: Classification for both A. satureioides and A. venosa was successful in all cases using only four variables: aluminium, iron, magnesium and sulphur content. The concentrations of the following elements were determined: Al, As, Ba, Ca, Cd, Co, Cr, Cu, Fe, K, La, Mg, Mn, Mo, Na, Ni, P, Pb, S, Sr, Ti, V, Y and Zn. CONCLUSIONS: This method is useful to identify both species in raw material in order to detect eventual errors of selection.

Determination of oleic acid in sunflower seeds by infrared spectroscopy and multivariate calibration method.

A method for the determination of oleic acid in sunflower seeds is proposed. One hundred samples of sunflower seeds were analyzed by near-infrared diffuse reflectance spectroscopy (NIRDRS). The direct measures were realized in ground and sifted seeds. The PLS multivariate calibration model was obtained using first derivate absorbance values as response matrix, while the oleic acid concentration matrix was obtained analyzing the seed samples by gas chromatography with a flame ionization detector (GC-FID). The NIRDRS-PLS model was validated externally using unknown samples of sunflower seeds. The accuracy and precision of the method was evaluated using GC as reference method. The following figures of merit (FOM) were obtained: LOD=3.4% (w/w); LOQ=11.3% (w/w); SEN=8x10(-5); SEL=0.15; analytical sensibility (gamma)=1.5 and linear range (LR)=18.1-89.2% (w/w). This method is useful for the fast determination of oleic acid in sunflower seeds and for quality control of raw materials.

Simultaneous determination of saccharin and aspartame in commercial noncaloric sweeteners using the PLS-2 multivariate calibration method and validation by capillary electrophoresis.

A new method to determine a mixture for sweetener sodium saccharin and aspartame in commercial noncaloric sweeteners is proposed. A classical full factorial design for standards was used in the calibration step to build the partial least-squares (PLS-2) model. Instrumental data were obtained by means of UV-visible spectrophotometry. Salicylic acid was used as an internal standard to evaluate the adjustment of the real samples to the PLS model. The concentration of analytes in the commercial samples was evaluated using the obtained model by UV spectral data. The PLS-2 method was validated by capillary zone electrophoresis (CZE), finding in all cases a relative error of less than 11% between the PLS-2 and the CZE methods. The proposed procedure was applied successfully to the determination of saccharin and aspartame in noncaloric commercial sweeteners.

Multielement analysis of argentinean lemon juices by instrumental neutronic activation analysis and their classification according to geographical origin.

Multielement analysis of lemon juices from different Argentinean regions was carried out by instrumental neutronic activation analysis (INAA) with the aim at developing a reliable method in the traceability of the origin of lemon juices. This work presents a characterization of 44 lemon juice samples selected from three different geographical origins in the Northwest region of Argentina. Multivariate chemometric techniques such principal component analysis and lineal discriminant analysis (LDA) were used with the aim of classifying the juices and identifying the most significant parameters. Eleven elements were determined (Br, As, Na, Rb, La, Cr, Sc, Fe, Co, Zn, and Sb). The analytical method was validated by analyzing the standard reference material IAEA V-10 (hay powder); the results are within +/-10% of the reported values for the majority of the elements. Biplots of LDA scores for the INAA data illustrate clear separation between each sample.

Simultaneous determination of sorbic and benzoic acids in commercial juices using the PLS-2 multivariate calibration method and validation by high performance liquid chromatography.

A new method to determine a mixture for preserving sorbic and benzoic acids in commercial juices is proposed. The PLS-2 model was obtained preparing 40 standard solutions adding concentration of sorbic and benzoic acid to filtered natural juices of apple, lemon, orange and grapefruit. The concentration of analytes in the commercial samples was evaluated using the obtained model by UV spectral data. The PLS-2 method was validated by high performance liquid chromatography (HPLC), finding a relative error less than 12% between the PLS-2 and HPLC methods in all cases.

Penicillamine determination using a tyrosinase micro-rotating biosensor.

Tyrosinase [EC 1.14.18.1], immobilized on a rotating disk, catalyzed the oxidation of catechols to o-benzoquinone, whose back electrochemical reduction was detected on glassy carbon electrode surface at -150mV versus Ag/AgCl/NaCl 3M. Thus, when penicillamine (PA) was added to the solution, this thiol-containing compound participate in Michael type addition reactions with o-benzoquinone to form the corresponding thioquinone derivatives, decreasing the reduction current obtained proportionally to the increase of its concentration. This method could be used for sensitive determination of PA in drug and human synthetic serum samples. A linear range of 0.02-80 microM (r=0.999) was obtained for amperometric determination of PA in buffered pH 7.0 solutions (0.1 M phosphate buffer). The biosensor has a reasonable reproducibility (R.S.D.<4.0%) and a very stable amperometric response toward this compound (more than 1 month).

Enzymatic rotating biosensor for cysteine and glutathione determination in a FIA system.

The high sensitivity that can be attained using an enzymatic system and mediated by catechols has been verified by on-line interfacing of a rotating biosensor and continuous flow/stopped-flow/continuous-flow processing. Horseradish peroxidase, HRP, [EC 1.11.1.7], immobilized on a rotating disk, in presence of hydrogen peroxide catalyzed the oxidation of catechols, whose back electrochemical reduction was detected on glassy carbon electrode surface at -150mV. Thus, when l-cysteine (Cys) or glutathione (GSH) was added to the solution, these thiol-containing compounds participate in Michael addition reactions with catechols to form the corresponding thioquinone derivatives, decreasing the peak current obtained proportionally to the increase of its concentration. Cys was used as the model thiol-containing compound for the study. The highest response for Cys was obtained around pH 7. This method could be used to determine Cys concentration in the range 0.05-90muM (r=0.998) and GSH concentration in the range 0.04-90muM (r=0.999). The determination of Cys and GSH were possible with a limit of detection of 0.7 and 0.3nM, respectively, in the processing of as many as 25 samples per hour. Current response of the HRP-rotating biosensor is not affected by the oxidized form of GSH and Cys (glutathione disulfide, GSSG, and l-cystine, respectively), by sulfur-containing and alkyl-amino compounds such as methionine and lysine, respectively. The interferences from easily oxidizable species such as ascorbic acid and uric acid are lowest.

Enzymatic rotating biosensor for ciprofloxacin determination.

The high sensitivity that can be attained using an enzymatic system and mediated by catechol has been verified by on-line interfacing of a rotating biosensor and continuous flow/stopped-flow/continuous-flow processing. Horseradish peroxidase, HRP [EC 1.11.1.7], immobilized on a rotating disk, in the presence of hydrogen peroxide, catalyzed the oxidation of catechol, whose back electrochemical reduction was detected on a glassy carbon electrode surface at -200mV. Thus, when ciprofloxacin (CF) was added to the solution, this piperazine-containing compound participate in Michael addition reactions with catechol to form the corresponding piperazine-quinone derivatives, decreasing the peak current obtained, in proportion with the increase of its concentration. The highest response for CF was obtained around pH 7. This method could be used to determine CF concentration in the range of 0.02-65muM (r=0.999). The determination of CF concentration was possible with a detection limit of 0.4nM, in the processing of as many as 25 samples per hour. Application of this analysis to different pharmaceutical samples containing CF supports the utility of the HRP-rotating biosensor.