A sensitive and simple method was developed for the classification of wines according to variety, geographical origin, and vintage using NMR-based metabonomics. Polyphenol-rich extracts were prepared from 67 varietal wines from the principal wine-producing regions of Greece, using adsorption resin XAD-4. 1D (1)H NMR spectra obtained from the corresponding extracts were segmented, integrated, and normalized, and the data were subjected to principal component analysis. The chemometric classification of wines according to their phenolic profile allows discrimination between wines from different wineries of the same wine-producing zone and between different vintages for wines of the same variety.
(1)H NMR based metabonomic approach was applied in order to monitor the alterations of plasma metabolic profile in Renal Cell Carcinoma (RCC) patients and controls. (1)H NMR spectra of plasma samples from 32 RCC patients and 13 controls (patients exhibiting benign urologic disease) were recorded and analyzed using multivariate statistical techniques. Alterations in the levels of LDL/VLDL, NAC, lactate, and choline were observed between RCC patients and controls discriminating these groups in Principal Component Analysis (PCA) plots. Post OSC PLS-DA presented a satisfactory clustering between T1 with T3 RCC patients. Decrease in plasma lipid concentrations in RCC patients was verified using conventional clinical chemistry analysis. The results suggest that combination of (1)H NMR spectroscopy with PCA has potential in cancer diagnosis; however, a limitation of the method to monitor RCC is that major biomarkers revealed (lipoproteins and choline) in this metabolic profile are not unique to RCC but may be the result of the presence of any malignancy.
Doxorubicin (DXR) is a commonly used antineoplastic agent; however, its use is limited due to cardiotoxicity. Oxidative stress and consequent alterations of cardiac energetics are involved in the development of DXR toxicity. Oleuropein (Oleu) is a phenolic antioxidant, present in olive tree, reported to confer protection against DXR cardiotoxicity. In this study, NMR based-metabonomics was applied to characterize the metabolic profile of the acute DXR cardiotoxicity in rats and to evaluate the metabolic alterations conferred by co-treatment with Oleu. Wistar rats were divided into six groups and treated as follows: control group with a single injection of 2 mL normal saline intraperitoneally (i.p.), DXR group with a single dose of 20 mg/kg, i.p and DXR plus Oleu groups with 20mg/kg DXR i.p., and 100 or 200 mg/kg/BW of Oleu i.p. for 5 or 3 consecutive days starting either 2 days before or on the day of DXR administration. Hearts were excised 72 h after DXR treatment and (1)H-NMR spectra of aqueous myocardium extracts were recorded. Principal Component Analysis (PCA) and Partial Least Square Discriminant Analysis (PLS-DA) revealed differences in the metabolic profile between control and DXR attributed to several metabolites. A number of them were quantified by integration of the NMR spectra. Myocardial levels of acetate and succinate were increased in DXR compared to controls, while branched amino acids were decreased. These results correlate with nonenzymatic conversion of pyruvate to acetate and of alpha-ketoglutarate to succinate by DXR free radicals. Oleu completely restored the changes of metabolites to the normal levels. Acetate and succinate constitute novel biomarkers related to DXR, and Oleu treatment aids the compensation of distressed energy metabolic pathways.
Toxicogenomics, resulting from the merge of conventional toxicology with functional genomics, being the scientific field studying the complex interactions between the cellular genome, toxic agents in the environment, organ dysfunction and disease state. When an organism is exposed to a toxic agent the cells respond by altering the pattern of gene expression. Genes are transcribed into mRNA, which in turn is translated into proteins that serve in a variety of cellular functions. Toxicogenomics through microarray technology, offers large-scale detection and quantification of mRNA transcripts, related to alterations in mRNA stability or gene regulation. This may prove advantageous in toxicological research. In the present review, the applications of toxicogenomics, especially to mechanistic and predictive toxicology are reported. The limitations arising from the use of this technology are also discussed. Additionally, a brief report of other approaches, using other -omic technologies (proteomics and metabonomics) that overcome limitations and give global information related to toxicity, is included.
Pharmacological agents and environmental pollutants can transfer from mother to fetus across the placental barrier, leading to reproductive toxic effects. Ex vivo human placental perfusion constitutes the most widely used method to study placental transfer and metabolism of drugs and chemicals. The aim of the present study was to evaluate whether quantitative structure-activity relationship (QSAR) methodology could serve as an effective alternative tool to estimate drugs and chemicals transport across the human placental barrier on the basis of easily interpretable molecular, physicochemical and structural properties. Multivariate data analysis (MVDA) was applied to a set of 88 structurally diverse drugs and chemicals to model placental transfer expressed by clearance index values compiled from literature sources. An adequate and robust QSAR model (r(2) = 0.73, Q(2) = 0.71, RMSEE = 0.15) was established, providing an informative illustration of the contributing physicochemical, molecular and structural properties of the compounds in placental transfer process. Descriptors reflecting the polarity of compounds proved to be the most important with a negative sign. Lipophilicity and, at a lower extent, molecular size parameters exerted positive contribution in the model. Thus, QSAR analysis may be considered as a promising alternative tool to support high-throughput screening of drugs and chemicals in respect to their transport across placental barrier.
Plasma NGAL concentrations were associated with patient age, hypertension, eGFR, creatinine and homocysteine concentrations and therapy with ACE inhibitors. The role of NGAL in the development of atherosclerosis needs to be further explored taking into consideration the uncontrolled effect of renal disease in atherosclerotic patients with multiple risk factors.
Liver fibrosis results from sustained wound healing response to chronic liver injury. Liver cirrhosis, the end stage of the fibrotic process, is characterized by disruption of the entire liver architecture and reduced hepatocyte regenerative ability. Hepatic stimulator substance (HSS) is a liver-specific growth factor triggering hepatocyte proliferation in vitro and in vivo. Previous studies have indicated the involvement of HSS in animal models of acute liver injury. The aim of the present study was to investigate the involvement of HSS in the process of fibrosis and cirrhosis induction. Liver fibrosis and cirrhosis were induced in rats by thioacetamide (TAA) administration (300 mg/l) in the drinking water for 3 months, and animals were killed at 0, 1, 2, and 3 months of treatment. TAA administration resulted in progressively increasing liver fibrosis, leading to the onset of cirrhosis at the end of the experimental time. HSS was continuously produced during the course of fibrosis and cirrhosis induction, peaking at the 2nd month of TAA treatment, coinciding with markers of hepatic proliferative capacity, as thymidine kinase activity and DNA biosynthesis. Significantly reduced HSS activity was noted in cirrhotic liver (3rd month). In this case, the exogenous HSS administration during the 3rd month of TAA treatment suppressed the onset of liver cirrhosis, stimulating the hepatic regenerative capacity. Our data indicate the active participation of HSS in the process of fibrosis and cirrhosis induction post-TAA treatment in rats, suggesting also the beneficial effect of HSS treatment against cirrhosis induction with future possible clinical implications.
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