PubMed

Related Articles Targeted metabolomics to understand the association between arsenic metabolism and diabetes-related outcomes: Preliminary evidence from the Strong Heart Family Study. Environ Res. 2018 Sep 27;168:146-157 Authors: Spratlen MJ, Grau-Perez M, Umans JG, Yracheta J, Best LG, Francesconi K, Goessler W, Bottiglieri T, Gamble MV, Cole SA, Zhao J, Navas-Acien A Abstract BACKGROUND: Inorganic arsenic exposure is ubiquitous and both exposure and inter-individual differences in its metabolism have been associated with cardiometabolic risk. A more efficient arsenic metabolism profile (lower MMA%, higher DMA%) has been associated with reduced risk for arsenic-related health outcomes. This profile, however, has also been associated with increased risk for diabetes-related outcomes. OBJECTIVES: The mechanism behind these conflicting associations is unclear; we hypothesized the one-carbon metabolism (OCM) pathway may play a role. METHODS: We evaluated the influence of OCM on the relationship between arsenic metabolism and diabetes-related outcomes (HOMA2-IR, waist circumference, fasting plasma glucose) using metabolomic data from an OCM-specific and P180 metabolite panel measured in plasma, arsenic metabolism measured in urine, and HOMA2-IR and FPG measured in fasting plasma. Samples were drawn from baseline visits (2001-2003) in 59 participants from the Strong Heart Family Study, a family-based cohort study of American Indians aged ≥14 years from Arizona, Oklahoma, and North/South Dakota. RESULTS: In unadjusted analyses, a 5% increase in DMA% was associated with higher HOMA2-IR (geometric mean ratio (GMR)= 1.13 (95% CI: 1.03, 1.25)) and waist circumference (mean difference=3.66 (0.95, 6.38). MMA% was significantly associated with lower HOMA2-IR and waist circumference. After adjustment for OCM-related metabolites (SAM, SAH, cysteine, glutamate, lysophosphatidylcholine 18.2, and three phosphatidlycholines), associations were attenuated and no longer significant. CONCLUSIONS: These preliminary results indicate that the association of lower MMA% and higher DMA% with diabetes-related outcomes may be influenced by OCM status, either through confounding, reverse causality, or mediation. PMID: 30316100 [PubMed - as supplied by publisher]

Related Articles From Plants to Pharmacy Shelf: Focus on Toxicology. Food Chem Toxicol. 2018 Oct 10;: Authors: Georgiev MI, Sieniawska E PMID: 30315823 [PubMed - as supplied by publisher]

Related Articles Urinary and Plasma Metabolomics Identify the Distinct Metabolic Profile of Disease State in Chronic Mouse Model of Multiple Sclerosis. J Neuroimmune Pharmacol. 2018 Oct 12;: Authors: Singh J, Cerghet M, Poisson LM, Datta I, Labuzek K, Suhail H, Rattan R, Giri S Abstract Identification of non-invasive biomarkers of disease progression in multiple sclerosis (MS) is critically needed for monitoring the disease progression and for effective therapeutic interventions. Urine is an attractive source for non-invasive biomarkers because it is easily obtained in the clinic. In search of a urine metabolite signature of progression in chronic experimental autoimmune encephalomyelitis (EAE), we profiled urine at the chronic stage of the disease (day 45 post immunization) by global untargeted metabolomics. Using a combination of high-throughput liquid-and-gas chromatography with mass spectrometry, we found 105 metabolites (P < 0.05) significantly altered at the chronic stage, indicating a robust alteration in the urine metabolite profile during disease. Assessment of altered metabolites against the Kyoto Encyclopedia of Genes and Genomes revealed distinct non-overlapping metabolic pathways and revealed phenylalanine-tyrosine and associated metabolism being the most impacted. Combined with previously performed plasma profiling, eight common metabolites were significantly altered in both of the biofluids. Metaboanalyst analysis of these common metabolites revealed that phenylalanine metabolism and Valine, leucine, and isoleucine biosynthetic pathways are central metabolic pathways in both bio-fluids and could be analyzed further, either for the discovery of therapeutics or biomarker development. Overall, our study suggests that urine and plasma metabolomics may contribute to the identification of a distinct metabolic fingerprint of EAE disease discriminating from the healthy control which may aid in the development of an objective non-invasive monitoring method for progressive autoimmune diseases like MS. Graphical Abstract Untargeted urinary metabolomics of a chronic mouse model of multiple sclerosis identified Phenylalanine, tyrosine & tryptophan metabolism as the significantly altered metabolic pathway. Eight common metabolites were identified when we combined urinary and plasma metabolic signature, which revealed a perturbation of Phenylalanine metabolism and valine, leucine & isoleucine metabolic pathways, involved in CNS dysfunction during diseases. The identified eight metabolic signature of urine and plasma may be of clinical relevance as potential biomarkers and guide towards the identification of specific metabolic pathways as novel drug targets. PMID: 30315511 [PubMed - as supplied by publisher]

Related Articles Measuring Rates of ATP Synthesis. Methods Mol Biol. 2019;1862:97-107 Authors: Bird MJ, Radenkovic S, Vermeersch P, Cassiman D Abstract Here, we offer you a high-throughput assay to measure the ATP synthesis capacity in cells or isolated mitochondria. More specifically, the assay is linked to the mitochondrial' electron transport chain components of your interest being either through complex I (with or without a linkage to pyruvate dehydrogenase activity), through complex II, or through the electron transport flavoprotein and complex I (β-oxidation of fatty acids). PMID: 30315462 [PubMed - in process]

Related Articles Measuring In Vivo Tissue Metabolism Using 13C Glucose Infusions in Mice. Methods Mol Biol. 2019;1862:67-82 Authors: Broekaert D, Fendt SM Abstract Metabolic alterations are a hallmark of cancer. While determining metabolic changes in vitro has delivered valuable insight into the metabolism of cancer cells, it emerges that determining the in vivo metabolism adds an additional layer of information. Here, we therefore describe how to measure the in vivo metabolism of cancer tissue using 13C glucose infusions in mice. PMID: 30315460 [PubMed - in process]

Related Articles 13C Tracer Analysis and Metabolomics in 3D Cultured Cancer Cells. Methods Mol Biol. 2019;1862:53-66 Authors: van Gorsel M, Elia I, Fendt SM Abstract Metabolomics and 13C tracer analysis are state-of-the-art techniques that allow determining the concentration of metabolites and the activity of metabolic pathways, respectively. Three dimensional (3D) cultures of cancer cells constitute an enriched in vitro environment that can be used to assay anchorage-independent growth, spheroid formation, and extracellular matrix production by (cancer) cells. Here, we describe how to perform metabolomics and 13C tracer analysis in 3D cultures of cancer cells. PMID: 30315459 [PubMed - in process]

Related Articles Measuring the Nutrient Metabolism of Adherent Cells in Culture. Methods Mol Biol. 2019;1862:37-52 Authors: Ogrodzinski MP, Teoh ST, Yu L, Broadwater D, Ensink E, Lunt SY Abstract Metabolite extraction from cells cultured in vitro enables the comprehensive measurement of intracellular metabolites. These extracts can be analyzed using techniques such as liquid chromatography-mass spectrometry (LC-MS). This chapter describes in detail a method for metabolite extraction from cultured adherent mammalian cells to collect both polar and nonpolar intracellular metabolites. This chapter also describes experimental design considerations for performing stable isotope labeling experiments, and the use of chemical derivatization to increase the number of compounds that can be detected using one chromatography method. PMID: 30315458 [PubMed - in process]

Related Articles A Protocol to Compare Methods for Untargeted Metabolomics. Methods Mol Biol. 2019;1862:1-15 Authors: Wang L, Naser FJ, Spalding JL, Patti GJ Abstract There are thousands of published methods for profiling metabolites with liquid chromatography/mass spectrometry (LC/MS). While many have been evaluated and optimized for a small number of select metabolites, very few have been assessed on the basis of global metabolite coverage. Thus, when performing untargeted metabolomics, researchers often question which combination of extraction techniques, chromatographic separations, and mass spectrometers is best for global profiling. Method comparisons are complicated because thousands of LC/MS signals (so-called features) in a typical untargeted metabolomic experiment cannot be readily identified with current resources. It is therefore challenging to distinguish methods that increase signal number due to improved metabolite coverage from methods that increase signal number due to contamination and artifacts. Here, we present the credentialing protocol to remove the latter from untargeted metabolomic datasets without having to identify metabolite structures. This protocol can be used to compare or optimize methods pertaining to any step of the untargeted metabolomic workflow (e.g., extraction, chromatography, mass spectrometer, informatic software, etc.). PMID: 30315456 [PubMed - in process]

Related Articles De novo NAD synthesis is required for intracellular replication of Coxiella burnetii, the causative agent of the neglected zoonotic disease Q fever. J Biol Chem. 2018 Oct 12;: Authors: Bitew MA, Khoo CA, Neha N, De Souza DP, Tull D, Wawegama NK, Newton HJ, Sansom FM Abstract Coxiella burnetii is an intracellular Gram-negative bacterium responsible for the important zoonotic disease Q fever. Improved genetic tools and the ability to grow this bacterium in host cell-free media has advanced the study of C. burnetii pathogenesis, but the mechanisms that allow it to survive inside the hostile phagolysosome remain incompletely understood. Previous screening of a transposon mutant library for replication within HeLa cells has suggested that nadB, encoding a putative L-aspartate oxidase required for de novo NAD synthesis, is needed for intracellular replication. Here, using genetic complementation of two independent nadB mutants and intracellular replication assays, we confirmed this finding. Untargeted metabolite analyses demonstrated key changes in metabolites in the NAD biosynthetic pathway in the nadB mutant compared with the wildtype, confirming the involvement of NadB in de novo NAD synthesis. Bioinformatic analysis revealed the presence of a functionally conserved arginine residue at position 275. Using site-directed mutagenesis to substitute this residue with leucine, which abolishes the activity of Escherichia coli NadB, and expression of wildtype and R275L GST-NadB fusion proteins in E. coli JM109, we found that purified recombinant wildtype GST-NadB has L-aspartate oxidase activity and that the R275L NadB variant is inactive. Complementation of the C. burnetii nadB mutant with a plasmid expressing this inactive R275L NadB failed to restore replication to wildtype levels, confirming the link between de novo NAD synthesis and intracellular replication of C. burnetii. This suggests that targeting this prokaryotic-specific pathway could advance the development of therapeutics to combat C. burnetii infections. PMID: 30315113 [PubMed - as supplied by publisher]

Related Articles Assessment of flux through oleoresin biosynthesis in epithelial cells of loblolly pine resin ducts. J Exp Bot. 2018 Oct 11;: Authors: Turner GW, Parrish AN, Zager JJ, Fischedick JT, Lange BM Abstract The shoot system of pines contains abundant resin ducts, which harbor oleoresins that play important roles in constitutive and inducible defenses. In a pilot study, we assessed the chemical diversity of oleoresins obtained from mature tissues of loblolly pine trees (Pinus taeda L.). Building on these data sets, we designed experiments to assess oleoresin biosynthesis in needles of 2-year-old saplings. Comparative transcriptome analyses of single cell types indicated that genes involved in the biosynthesis of oleoresins are significantly enriched in isolated epithelial cells of resin ducts, compared with those expressed in mesophyll cells. Simulations using newly developed genome-scale models of epithelial and mesophyll cells, which incorporate our data on oleoresin yield and composition as well as gene expression patterns, predicted that heterotrophic metabolism in epithelial cells involves enhanced levels of oxidative phosphorylation and fermentation (providing redox and energy equivalents). Furthermore, flux was predicted to be more evenly distributed across the metabolic network of mesophyll cells, which, in contrast to epithelial cells, do not synthesize high levels of specialized metabolites. Our findings provide novel insights into the remarkable specialization of metabolism in epithelial cells. PMID: 30312429 [PubMed - as supplied by publisher]

Related Articles Characterising the plasma metabolome during 14 days live high, train low simulated altitude: A metabolomic approach. Exp Physiol. 2018 Oct 12;: Authors: Lawler NG, Abbiss CR, Gummer JP, Broadhurst DI, Govus AD, Fairchild TJ, Thompson KG, Garvican-Lewis LA, Gore CJ, Maker GL, Trengove RD, Peiffer JJ Abstract NEW FINDING: What is the central question of this study? To determine how 14 days of LHTL at simulated altitude alters an individual's metabolomic/metabolic profile? What is the main finding and its importance? This study demonstrated that ∼200 h of moderate simulated altitude exposure showed greater variance in measured metabolites between-person compared to within-person, which indicates individual variability during the adaptive phase to altitude exposure. In addition, metabolomics results indicate altitude alters multiple metabolic pathways of which the time course of these pathways is different over 14 days of altitude exposure. These findings support previous literature and provide new information into the acute adaptation response to altitude. ABSTRACT: Purpose The purpose of this study was to determine the influence of 14 days of normobaric hypoxic altitude exposure at 3000 m on the human plasma metabolomic profile. Methods Over 14 days, ten well trained endurance runners (six males, four females; 29 ± 7 y) lived at 3000 m simulated altitude, accumulating 196.4 ± 25.6 h of hypoxic exposure, and trained at ∼600 m. Resting plasma samples were collected at baseline, day 3 and day 14 of altitude exposure and stored at -80 °C. Plasma samples were analysed using liquid chromatography-high resolution mass spectrometry (LC-HRMS) to construct a metabolite profile of altitude exposure. Results Mass spectrometry of plasma identified 36 metabolites, of which eight were statistically significant (pFDR 0.1) from baseline to either day 3 or day 14. Specifically, changes in plasma metabolites relating to amino acid metabolism (tyrosine and proline), glycolysis (adenosine) and purine metabolism (adenosine) were observed during altitude exposure. Principal component canonical variate analysis showed significant discrimination between group means (p < 0.05) with canonical variate (CV) 1 describing non-linear recovery trajectory from baseline to day 3 and then back to baseline by day 14. Conversely, CV2 described a weaker non-recovery trajectory and increase from baseline to day 3, with a further increase from day 3 to day 14. Conclusion The current study demonstrates that metabolomics can be a useful tool to monitor metabolic changes associated with altitude exposure. Furthermore, it is apparent that altitude exposure alters multiple metabolic pathways, and the time course of these changes is different over 14 days of altitude exposure. This article is protected by copyright. All rights reserved. PMID: 30311980 [PubMed - as supplied by publisher]

Related Articles In vivo toxicology of carbon dots by 1H NMR-based metabolomics. Toxicol Res (Camb). 2018 Sep 01;7(5):834-847 Authors: Hong W, Liu Y, Li MH, Xing YX, Chen T, Fu YH, Jiang L, Zhao H, Jia AQ, Wang JS Abstract Owing to the promising applications of C-dots in biomedical engineering, concerns about their safety have drawn increasing attention recently. In this study, mice were intraperitoneally injected at different C-dot concentrations (0, 6.0, 12.0 and 24.0 mg kg-1) once every 2 days for 30 days. A 1H NMR-based metabolic approach supplemented with biochemical analysis and histopathology was used for the first time to explore the toxicity of C-dots in vivo. Histopathological inspection revealed that C-dots did not induce any obvious impairment in tissues. Biochemical assays showed no significant alterations of most measured biochemical parameters in tissues and serum, except for a slight reduction of the albumin level in serum as well as AChE activity in the liver and kidneys. Orthogonal signal correction-partial least squares-discriminant analysis (OSC-PLS-DA) of NMR profiles supplemented with correlation network analysis and SUS-plots disclosed that C-dots not only triggered the immune system but also disturbed the function of cell membranes as well as the normal liver clearance, indicating that the 1H NMR based metabolomics approach provided deep insights into the toxicity of C-dots in vivo and gained an advantage over traditional toxicological means, and should be helpful for the understanding of its toxic mechanism. PMID: 30310661 [PubMed]

Related Articles 1H-NMR-based metabolic profiling of healthy individuals and high-resolution CT-classified phenotypes of COPD with treatment of tiotropium bromide. Int J Chron Obstruct Pulmon Dis. 2018;13:2985-2997 Authors: Tan LC, Yang WJ, Fu WP, Su P, Shu JK, Dai LM Abstract Background: Heterogeneity of COPD results in different therapeutic effects for different patients receiving the same treatment. COPD patients need to be individually treated according to their own characteristics. The purpose of this study was to explore the differences in different CT phenotypic COPD by molecular metabolites through the use of metabolomics. Methods: According to the characteristics of CT imaging, 42 COPD patients were grouped into phenotype E (n=20) or phenotype M (n=24). Each COPD patient received tiotropium bromide powder for inhalation for a therapeutic period of 3 months. All subjects were assigned into phenotype E in pre-therapy (EB, n=20), phenotype E in post-therapy (EA, n=20), phenotype M in pre-therapy (MB, n=22), phenotype M in post-therapy (MA, n=22), or normal control (N, n=24). The method of metabolomics based on 1H nuclear magnetic resonance (1H-NMR) was used to compare the changes in serum metabolites between COPD patients and normal controls and between different phenotypes of COPD patients in pre- and post-therapy. Results: Patients with COPD phenotype E responded better to tiotropium bromide than patients with COPD phenotype M in terms of pulmonary function and COPD assessment test scores. There were differences in metabolites in COPD patients vs normal control people. Differences were also observed between different COPD phenotypic patients receiving the treatment in comparison with those who did not receive treatment. The changes of metabolites involved lactate, phenylalanine, fructose, glycine, asparagine, citric acid, pyruvic acid, proline, acetone, ornithine, lipid, pyridoxine, maltose, betaine, lipoprotein, and so on. These identified metabolites covered the metabolic pathways of amino acids, carbohydrates, lipids, genetic materials, and vitamin. Conclusion: The efficacy of tiotropium bromide on COPD phenotype E is better than that of phenotype M. Metabolites detected by 1H-NMR metabolomics have potentialities of differentiation of COPD and healthy people, discrimination of different COPD phenotypes, and giving insight into the individualized treatment of COPD. PMID: 30310274 [PubMed - in process]

Related Articles Hydroxyurea Treated β-Thalassemia Children Demonstrate a Shift in Metabolism Towards Healthy Pattern. Sci Rep. 2018 Oct 11;8(1):15152 Authors: Iqbal A, Ansari SH, Parveen S, Khan IA, Siddiqui AJ, Musharraf SG Abstract Augmentation of fetal hemoglobin (HbF) production has been an enduring therapeutic objective in β-thalassemia patients for which hydroxyurea (HU) has largely been the drug of choice and the most cost-effective approach. A serum metabolomics study on 40 patients with β-thalassemia prior to and after administration of HU was done along with healthy controls. Treated patients were divided further into non-responders (NR), partial (PR) and good (GR) per their response. 25 metabolites that were altered before HU therapy at p ≤ 0.05 and fold change >2.0 in β-thalassemia patients; started reverting towards healthy group after HU treatment. A prediction model based on another set of 70 HU treated patients showed a good separation of GR from untreated β-thalassemia patients with an overall accuracy of 76.37%. Metabolic pathway analysis revealed that various important pathways that were disturbed in β-thalassemia were reverted after treatment with HU and among them linoleic acid pathway was most impactfully improved in HU treated patients which is a precursor of important signaling molecules. In conclusion, this study indicates that HU is a good treatment option for β-thalassemia patients because in addition to reducing blood transfusion burden it also ameliorates disease complications by shifting body metabolism towards normal. PMID: 30310134 [PubMed - in process]

Related Articles Sample management for clinical biochemistry assays: Are serum and plasma interchangeable specimens? Crit Rev Clin Lab Sci. 2018 Oct 12;:1-21 Authors: Lima-Oliveira G, Monneret D, Guerber F, Guidi GC Abstract The constrained economic context leads laboratories to centralize their routine analyses on high-throughput platforms, to which blood collection tubes are sent from peripheral sampling sites that are sometimes distantly located. Providing biochemistry results as quickly as possible implies to consolidate the maximum number of tests on a minimum number of blood collection tubes, mainly serum tubes and/or tubes with anticoagulants. However, depending on the parameters and their pre-analytical conditions, the type of matrix - serum or plasma - may have a significant impact on results, which is often unknown or underestimated in clinical practice. Importantly, the matrix-related effects may be a limit to the consolidation of analyses on a single tube, and thus must be known by laboratory professionals. The purpose of the present critical review is to put forward the main differences between using serum and plasma samples on clinical biochemistry analyses, in order to sensitize laboratory managers to the need for standardization. To enrich the debate, we also provide an additional comparison of serum and plasma concentrations for approximately 30 biochemistry parameters. Properties, advantages, and disadvantages of serum and plasma are discussed from a pre-analytical standpoint - before, during, and after centrifugation - with an emphasis on the importance of temperature, delay, and transport conditions. Then, differences in results between these matrices are addressed for many classes of biochemistry markers, particularly proteins, enzymes, electrolytes, lipids, circulating nucleic acids, metabolomics markers, and therapeutic drugs. Finally, important key-points are proposed to help others choose the best sample matrix and guarantee quality of clinical biochemistry assays. Moreover, awareness of the implications of using serum and plasma samples on various parameters assayed in the laboratory is an important requirement to ensure reliable results and improve patient care. PMID: 30309270 [PubMed - as supplied by publisher]

Related Articles Utility of Integrated Analysis of Pharmacogenomics and Pharmacometabolomics in Early Phase Clinical Trial: A Case Study of a New Molecular Entity. Genomics Inform. 2018 Sep;16(3):52-58 Authors: Oh J, Yi S, Gu N, Shin D, Yu KS, Yoon SH, Cho JY, Jang IJ Abstract In this report, we present a case study of how pharmacogenomics and pharmacometabolomics can be useful to characterize safety and pharmacokinetic profiles in early phase new drug development clinical trials. During conducting a first-in-human trial for a new molecular entity, we were able to determine the mechanism of dichotomized variability in plasma drug concentrations, which appeared closely related to adverse drug reactions (ADRs) through integrated omics analysis. The pharmacogenomics screening was performed from whole blood samples using the Affymetrix DMET (Drug-Metabolizing Enzymes and Transporters) Plus microarray, and confirmation of genetic variants was performed using real-time polymerase chain reaction. Metabolomics profiling was performed from plasma samples using liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. A GSTM1 null polymorphism was identified in pharmacogenomics test and the drug concentrations was higher in GSTM1 null subjects than GSTM1 functional subjects. The apparent drug clearance was 13-fold lower in GSTM1 null subjects than GSTM1 functional subjects (p ＜ 0.001). By metabolomics analysis, we identified that the study drug was metabolized by cysteinylglycine conjugation in GSTM functional subjects but those not in GSTM1 null subjects. The incidence rate and the severity of ADRs were higher in the GSTM1 null subjects than the GSTM1 functional subjects. Through the integrated omics analysis, we could understand the mechanism of inter-individual variability in drug exposure and in adverse response. In conclusion, integrated multi-omics analysis can be useful for elucidating the various characteristics of new drug candidates in early phase clinical trials. PMID: 30309203 [PubMed]

Related Articles Uptake and toxic effects of triphenyl phosphate on freshwater microalgae Chlorella vulgaris and Scenedesmus obliquus: Insights from untargeted metabolomics. Sci Total Environ. 2019 Feb 10;650(Pt 1):1239-1249 Authors: Wang L, Huang X, Lim DJ, Laserna AKC, Li SFY Abstract The flame retardant triphenyl phosphate (TPhP) has been widely detected in surface waters. Yet, little information is known regarding its impact on microalgae. We investigated the uptake and toxicity of TPhP on two freshwater microalgae Chlorella vulgaris (CV) and Scenedesmus obliquus (SO) after exposure to 10 μg/l-10 mg/l for 5 days. The presence of microalgae significantly enhanced TPhP degradation, with the final concentrations dropped to 5.5-35.1% of the original concentrations. Most of the medium TPhP were sorbed and transformed by microalgae in just one day. Growth of CV was inhibited in a concentration-dependent manner, whereas growth of SO were only inhibited significantly at 10 mg/l TPhP exposure. Mass spectrometry-based untargeted metabolomics revealed concentration- and species-dependent metabolic responses. Exposure to TPhP in CV resulted in enhanced respiration (increase of fumarate and malate) and osmoregulation (increase of sucrose and myo-inositol), synthesis of membrane lipids (accumulation of monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG), decrease of lysoglycerolipids, fatty acids, and glyceryl-glucoside). Exposure to TPhP in SO resulted in enhanced osmoregulation (increase of valine, proline, and raffinose) and lipolysis (decrease of MGDG, accumulation of fatty acids, lysophospholipids, and glycerol phosphate). Although chlorophyll a and b contents did not change significantly, decrease of chlorophyll derivatives was observed in both CV and SO at high exposure concentrations. Further bioassays confirmed that CV exhibited enhanced membrane integrity and decreased cellular reactive oxygen species (ROS) possibly as a defense strategy, whereas SO showed disruption of membrane integrity and induction of ROS at 10 mg/l exposure. This study demonstrated the potential of microalgae to remove TPhP in water, and offered new insights for the risk assessment of TPhP on freshwater microalgae using metabolomics. PMID: 30308812 [PubMed - in process]

28 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2018/10/12PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

22 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2018/10/10PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Assessing pH-dependent toxicity of fluoxetine in embryonic zebrafish using mass spectrometry-based metabolomics. Sci Total Environ. 2018 Oct 01;650(Pt 2):2731-2741 Authors: Mishra P, Gong Z, Kelly BC Abstract While it is well known that fluoxetine is more toxic to aquatic organisms at high pH, the metabolic dysregulations related to observed pH-dependent effects are still poorly understood. In the present study, we utilized a gas chromatography mass spectrometry (GC-MS) based metabolomics approach to assess metabolomic profile changes in developing zebrafish embryos following exposure (2 hpf-96 hpf) to different concentrations of fluoxetine at three environmentally relevant pH values (7.0, 8.0, and 9.0). Multivariate data analyses and pathway analyses were used to assess metabolomic profile changes and elicit important biochemical information regarding pH-dependent toxicity of fluoxetine. Overall, the affected biochemical functions related to fluoxetine exposure included amino acid metabolism, energy metabolism, nitrogenous waste excretion and osmolyte functions. While fluoxetine exposure (56 μg/L, 70 μg/L and 500 μg/L) caused no significant changes at pH 7, 500 μg/L and 70 μg/L fluoxetine was differentiated from the controls at pH 8 and pH 9 respectively. Three, eight and seven metabolites were identified as the most adversely affected at pH 7, 8 and 9, respectively. The altered metabolites associated with fluoxetine toxicity at high pH included urea, glycine and d-glucose 6-phosphate. Exposure to 70 μg/L fluoxetine, did not cause significant metabolomic profile changes at pH 7, However, the results indicate that this exposure concentration at pH and 9 can cause significant metabolic dysregulation related to apoptosis and oxidative stress. Increasing aqueous pH progressively enhanced fluoxetine induced toxicity for the 70 μg/L exposure group. The observed impacts included higher energy consumption at pH 7, a breakdown of reserve energy to supplement energy demand at pH 8 and impaired lipid metabolism at pH 9. This study provides important information regarding molecular-level effects related to pH-dependent exposure of fluoxetine in embryonic zebrafish. PMID: 30296778 [PubMed - as supplied by publisher]