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Karimpour, Masoumeh
Publications (8 of 8) Show all publications
Gouveia-Figueira, S. C., Karimpour, M., Bosson, J. A., Blomberg, A., Unosson, J., Sehlstedt, M., . . . Nording, M. L. (2018). Mass spectrometry profiling reveals altered plasma levels of monohydroxy fatty acids and related lipids in healthy humans after controlled exposure to biodiesel exhaust. Analytica Chimica Acta, 1018, 62-69
Open this publication in new window or tab >>Mass spectrometry profiling reveals altered plasma levels of monohydroxy fatty acids and related lipids in healthy humans after controlled exposure to biodiesel exhaust
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2018 (English)In: Analytica Chimica Acta, ISSN 0003-2670, E-ISSN 1873-4324, Vol. 1018, p. 62-69Article in journal (Refereed) Published
Abstract [en]

Experimental human exposure studies are an effective tool to study adverse health effects from acute inhalation of particulate matter and other constituents of air pollution. In this randomized and double-blinded crossover study, we investigated the systemic effect on bioactive lipid metabolite levels after controlled biodiesel exhaust exposure of healthy humans and compared it to filtered air at a separate exposure occasion. Eicosanoids and other oxylipins, as well as endocannabinoids and related lipids, were quantified in plasma from 14 healthy volunteers at baseline and at three subsequent time points (2, 6, and 24 h) after 1 h exposure sessions. Protocols based on liquid chromatography (LC) coupled to tandem mass spectrometry (MS/MS) methods were developed to detect temporal changes in circulating levels after biodiesel exhaust exposure. The exhaust was generated by a diesel engine fed with an undiluted rapeseed methyl ester fuel. Among the 51 analyzed lipid metabolites, PGF(2 alpha), 9,10-DiHOME, 9-HODE, 5-HETE, 11-HETE, 12-HETE, and DEA displayed significant responsiveness to the biodiesel exhaust exposure as opposed to filtered air. Of these, 9-HODE and 5-HETE at 24 h survived the 10% false discovery rate cutoff (p < 0.003). Hence, the majority of the responsive lipid metabolites were monohydroxy fatty acids. We conclude that it is possible to detect alterations in circulating bioactive lipid metabolites in response to biodiesel exhaust exposure using LC-MS/MS, with emphasis on metabolites with inflammation related properties and implications on cardiovascular health and disease. These observations aid future investigations on air pollution effects, especially with regard to cardiovascular outcomes.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
Oxylipin, Endocannabinoid, Eicosanoid, Mass spectrometry, Rapeseed methyl ester, Inflammation
National Category
Occupational Health and Environmental Health Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:umu:diva-148622 (URN)10.1016/j.aca.2018.02.032 (DOI)000428798200008 ()29605135 (PubMedID)
Funder
Swedish Research Council, 2010-303AFA Insurance, 130320
Available from: 2018-06-26 Created: 2018-06-26 Last updated: 2018-06-26Bibliographically approved
Gouveia-Figueira, S., Karimpour, M., Bosson, J. A., Blomberg, A., Unosson, J., Pourazar, J., . . . Nording, M. L. (2017). Mass spectrometry profiling of oxylipins, endocannabinoids, and N-acylethanolamines in human lung lavage fluids reveals responsiveness of prostaglandin E2 and associated lipid metabolites to biodiesel exhaust exposure. Analytical and Bioanalytical Chemistry, 409(11), 2967-2980
Open this publication in new window or tab >>Mass spectrometry profiling of oxylipins, endocannabinoids, and N-acylethanolamines in human lung lavage fluids reveals responsiveness of prostaglandin E2 and associated lipid metabolites to biodiesel exhaust exposure
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2017 (English)In: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 409, no 11, p. 2967-2980Article in journal (Refereed) Published
Abstract [en]

The adverse effects of petrodiesel exhaust exposure on the cardiovascular and respiratory systems are well recognized. While biofuels such as rapeseed methyl ester (RME) biodiesel may have ecological advantages, the exhaust generated may cause adverse health effects. In the current study, we investigated the responses of bioactive lipid mediators in human airways after biodiesel exhaust exposure using lipidomic profiling methods. Lipid mediator levels in lung lavage were assessed following 1-h biodiesel exhaust (average particulate matter concentration, 159 mu g/m(3)) or filtered air exposure in 15 healthy individuals in a double-blinded, randomized, controlled, crossover study design. Bronchoscopy was performed 6 h post exposure and lung lavage fluids, i.e., bronchial wash (BW) and bronchoalveolar lavage (BAL), were sequentially collected. Mass spectrometry methods were used to detect a wide array of oxylipins (including eicosanoids), endocannabinoids, Nacylethanolamines, and related lipid metabolites in the collected BWand BAL samples. Six lipids in the human lung lavage samples were altered following biodiesel exhaust exposure, three from BAL samples and three from BW samples. Of these, elevated levels of PGE2, 12,13-DiHOME, and 13-HODE, all of which were found in BAL samples, reached Bonferroni-corrected significance. This is the first study in humans reporting responses of bioactive lipids following biodiesel exhaust exposure and the most pronounced responses were seen in the more peripheral and alveolar lung compartments, reflected by BAL collection. Since the responsiveness and diagnostic value of a subset of the studied lipid metabolites were established in lavage fluids, we conclude that our mass spectrometry profiling method is useful to assess effects of human exposure to vehicle exhaust.

Place, publisher, year, edition, pages
SPRINGER HEIDELBERG, 2017
Keywords
BAL, BW, Lipidome, Air pollution, Bronchoscopy, Eicosanoid
National Category
Occupational Health and Environmental Health
Identifiers
urn:nbn:se:umu:diva-134210 (URN)10.1007/s00216-017-0243-8 (DOI)000398515900019 ()28235994 (PubMedID)
Available from: 2017-06-20 Created: 2017-06-20 Last updated: 2018-06-09Bibliographically approved
Surowiec, I., Karimpour, M., Gouveia-Figueira, S., Wu, J., Unosson, J., Bosson, J. A., . . . Nording, M. L. (2016). Multi-platform metabolomics assays for human lung lavage fluids in an air pollution exposure study. Analytical and Bioanalytical Chemistry, 408(17), 4751-4764
Open this publication in new window or tab >>Multi-platform metabolomics assays for human lung lavage fluids in an air pollution exposure study
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2016 (English)In: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 408, no 17, p. 4751-4764Article in journal (Refereed) Published
Abstract [en]

Metabolomics protocols are used to comprehensively characterize the metabolite content of biological samples by exploiting cutting-edge analytical platforms, such as gas chromatography (GC) or liquid chromatography (LC) coupled to mass spectrometry (MS) assays, as well as nuclear magnetic resonance (NMR) assays. We have developed novel sample preparation procedures combined with GC-MS, LC-MS, and NMR metabolomics profiling for analyzing bronchial wash (BW) and bronchoalveolar lavage (BAL) fluid from 15 healthy volunteers following exposure to biodiesel exhaust and filtered air. Our aim was to investigate the responsiveness of metabolite profiles in the human lung to air pollution exposure derived from combustion of biofuels, such as rapeseed methyl ester biodiesel, which are increasingly being promoted as alternatives to conventional fossil fuels. Our multi-platform approach enabled us to detect the greatest number of unique metabolites yet reported in BW and BAL fluid (82 in total). All of the metabolomics assays indicated that the metabolite profiles of the BW and BAL fluids differed appreciably, with 46 metabolites showing significantly different levels in the corresponding lung compartments. Furthermore, the GC-MS assay revealed an effect of biodiesel exhaust exposure on the levels of 1-monostearylglycerol, sucrose, inosine, nonanoic acid, and ethanolamine (in BAL) and pentadecanoic acid (in BW), whereas the LC-MS assay indicated a shift in the levels of niacinamide (in BAL). The NMR assay only identified lactic acid (in BW) as being responsive to biodiesel exhaust exposure. Our findings demonstrate that the proposed multi-platform approach is useful for wide metabolomics screening of BW and BAL fluids and can facilitate elucidation of metabolites responsive to biodiesel exhaust exposure.

National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:umu:diva-121129 (URN)10.1007/s00216-016-9566-0 (DOI)000378725200024 ()
Available from: 2016-05-26 Created: 2016-05-26 Last updated: 2018-06-07Bibliographically approved
Karimpour, M. (2016). Multi-platform metabolomics assays to study the responsiveness of the human plasma and lung lavage metabolome. (Doctoral dissertation). Umeå: Umeå University
Open this publication in new window or tab >>Multi-platform metabolomics assays to study the responsiveness of the human plasma and lung lavage metabolome
2016 (English)Doctoral thesis, comprehensive summary (Other academic) [Artistic work]
Alternative title[sv]
Multi-plattform metabolomik för analys av förändringar hos det humana metabolomet i plasma och lungsköljvätska
Abstract [en]

Metabolomics as a field has been used to track changes and perturbations in the human body by investigating metabolite profiles indicating the change of metabolite levels over time and in response to different challenges. In this thesis work, the main focus was on applying multiplatform-metabolomics to study the human metabolome following exposure to perturbations, such as diet (in the form of a challenge meal) and exhaust emissions (air pollution exposure in a controlled setting). The cutting-edge analytical platforms used for this purpose were nuclear magnetic resonance (NMR), as well as gas chromatography (GC) and liquid chromatography (LC) coupled to mass spectrometry (MS). Each platform offered unique characterization features, allowing detection and identification of a specific range of metabolites. The use of multiplatform-metabolomics was found to enhance the metabolome coverage and to provide complementary findings that enabled a better understanding of the biochemical processes reflected by the metabolite profiles. Using non-targeted analysis, a wide range of unknown metabolites in plasma were identified during the postprandial stage after a well-defined challenge meal (in Paper I). In addition, a considerable number of metabolites were detected and identified in lung lavage fluid after biodiesel exhaust exposure compared to filtered air exposure (in Paper II). In parallel, using targeted analysis, both lung lavage and plasma fatty acid metabolites were detected and quantified in response to filtered air and biodiesel exhaust exposure (in Paper III and IV).

Data processing of raw data followed by data analysis, using both univariate and multivariate methods, enabled changes occurring in metabolites levels to be screened and investigated. For the initial pilot postprandial study, the aim was to investigate the plasma metabolome response after a well-defined meal during the postprandial stage for two types of diet. It was found that independent of the background diet type, levels of metabolites returned to their baseline levels after three hours. This finding was taken into consideration for the biodiesel exhaust exposures studies, designed to limit the impact of dietary effects. Both targeted and non-targeted approaches resulted in important findings. For instance, different metabolite profiles were detected in bronchial wash (BW) compared to bronchoalveolar lavage (BAL) fluid with mainly NMR and LC-MS. Furthermore, biodiesel exhaust exposure resulted in different metabolite profiles as observed by GC-MS, especially in BAL. In addition, fatty acid metabolites in BW, BAL, and plasma were shown to be responsive to biodiesel exhaust exposure, as measured by a targeted LC-MS/MS protocol. In summary, the new analytical methods developed to investigate the responsiveness of the human plasma and lung lavage metabolome proved to be useful in an analytical perspective, and provided important biological findings. However, further studies are needed to validate these results.

Abstract [sv]

Metabolomik har använts för att spåra förändringar och störningar i kroppens funktioner genom undersökning av metabolit-profiler. I detta avhandlingasarbete har huvudfokus varit på tillämpning av flera olika analytiska plattformar för metabolomikstudier av det mänskliga metabolomet efter exponering för olika kost och avgasutsläpp från biodieselbränsle. De sofistikerade analytiska plattformarna som användes för detta ändamål var kärnmagnetisk resonans (NMR), samt gaskromatografi (GC) och vätskekromatografi (LC) kopplat till masspektrometri (MS). Varje plattform erbjöd unika karakteriseringsmöjligheter med detektion och identifiering av specifika grupper av metaboliter. Användningen av multipattformmetabolomik förbättrade täckningen av metabolomet och genererade kompletterande resultat som möjliggjorde en bättre förståelse av de biokemiska processer som reflekteras av metabolitprofilerna. Med hjälp av breda analyser har ett stort antal okända metaboliter i plasma identifierats under den postprandial fasen efter en väldefinerad måltid (i Paper I). Dessutom har ett stort antal metaboliter påvisats och identifierats i lungsköljvätska efter exponering av biodieselavgaser jämfört med kontollexponering med filtrerad luft (i Paper II). Parallellt med dessa breda analyser har också riktade analyser genomförts av både lungsköljvätska och plasma. Därigenom har bioaktiva lipider detekterats och kvantifieras efter avgasexponering och resultaten har jämförts med filtrerad luft som kontrollexponering (Paper III och IV). Processning av rådata följt av dataanalys, med både univariata och multivariata metoder möjliggjorde screening och fördjupad undersökning av förändringen i metabolitnivåer. I den första pilotstudien av postprandiala nivåer var syftet att undersöka responsen i plasmametabolomet efter en väldefinierad måltid under den postprandiala fasen vid två olika typer av kost. Resultaten visade att oberoende av kosten, så återvände metabolitnivåerna till sina baslinjenivåer tre timmar efter måltiden. Detta togs i beaktande vid exponeringsstudierna för biodieselavgaser, som designades så att dietens inverkan minimerades. Både breda och riktade analyser resulterade i viktiga resultat. Exempelvis så detekterades olika metabolitprofiler i bronkiell sköljvätska (BW) jämfört med bronkoalveolär sköljvätska (BAL), speciellt med NMR och LC-MS. Dessutom resulterade avgasexponering i förändrade metabolitprofiler, observerade med GC-MS, särskilt i BAL. Dessutom uppvisade fettsyrametaboliter i BW, BAL och plasma förändrade halter efter avgasexponering, uppmätt genom en riktad LC-MS/MS-analys. Sammanfattningsvis så visade sig de nya metoderna som utvecklats för att undersöka  förändringar i metabolithalterna i plasma och lungsköljvätska fungera väl ur ett analytiskt perspektiv och resulterade i viktiga biologiska fynd. Fördjupade studier behövs dock för att validera resultaten.

Place, publisher, year, edition, pages
Umeå: Umeå University, 2016. p. 40
Keywords
LC/MS, GC/MS, NMR, metabolomics, metabolite, exposure, postprandial, plasma, lung lavage, BW, BW, data analysis, univariate analysis, multivariate analysis
National Category
Analytical Chemistry Occupational Health and Environmental Health Nutrition and Dietetics
Identifiers
urn:nbn:se:umu:diva-120591 (URN)978-91-7601-506-3 (ISBN)
Public defence
2016-06-15, KB3A9, Kemiska institutionen, Department of Chemistry, Umeå, 10:00 (English)
Opponent
Supervisors
Available from: 2016-05-27 Created: 2016-05-17 Last updated: 2018-06-07Bibliographically approved
Karimpour, M., Surowiec, I., Wu, J., Gouveia-Figueira, S., Pinto, R., Trygg, J., . . . Nording, M. L. (2016). Postprandial metabolomics: A pilot mass spectrometry and NMR study of the human plasma metabolome in response to a challenge meal. Analytica Chimica Acta, 908, 121-131
Open this publication in new window or tab >>Postprandial metabolomics: A pilot mass spectrometry and NMR study of the human plasma metabolome in response to a challenge meal
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2016 (English)In: Analytica Chimica Acta, ISSN 0003-2670, E-ISSN 1873-4324, Vol. 908, p. 121-131Article in journal (Refereed) Published
Abstract [en]

The study of postprandial metabolism is relevant for understanding metabolic diseases and characterizing personal responses to diet. We combined three analytical platforms – gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) – to validate a multi-platform approach for characterizing individual variation in the postprandial state. We analyzed the postprandial plasma metabolome by introducing, at three occasions, meal challenges on a usual diet, and 1.5 years later, on a modified background diet. The postprandial response was stable over time and largely independent of the background diet as revealed by all three analytical platforms. Coverage of the metabolome between NMR and GC-MS included more polar metabolites detectable only by NMR and more hydrophobic compounds detected by GC-MS. The variability across three separate testing occasions among the identified metabolites was in the range of 1.1–86% for GC-MS and 0.9–42% for NMR in the fasting state at baseline. For the LC-MS analysis, the coefficients of variation of the detected compounds in the fasting state at baseline were in the range of 2–97% for the positive and 4–69% for the negative mode. Multivariate analysis (MVA) of metabolites detected with GC-MS revealed that for both background diets, levels of postprandial amino acids and sugars increased whereas those of fatty acids decreased at 0.5 h after the meal was consumed, reflecting the expected response to the challenge meal. MVA of NMR data revealed increasing postprandial levels of amino acids and other organic acids together with decreasing levels of acetoacetate and 3-hydroxybutanoic acid, also independent of the background diet. Together these data show that the postprandial response to the same challenge meal was stable even though it was tested 1.5 years apart, and that it was largely independent of background diet. This work demonstrates the efficacy of a multi-platform metabolomics approach followed by multivariate and univariate data analysis for a broad-scale screen of the individual metabolome, particularly for studies using repeated measures to determine dietary response phenotype.

Place, publisher, year, edition, pages
Elsevier: , 2016
Keywords
Metabolomics, Postprandial, Multi-platform analysis, Data analysis, Mass spectrometry, Nucleic magnetic resonance
National Category
Analytical Chemistry Nutrition and Dietetics
Identifiers
urn:nbn:se:umu:diva-120593 (URN)10.1016/j.aca.2015.12.009 (DOI)000368825700011 ()
Funder
Swedish Research Council Formas, 2010-303
Available from: 2016-05-17 Created: 2016-05-17 Last updated: 2018-06-07Bibliographically approved
Ghorbanzadeh, M., Fatemi, M. H. & Karimpour, M. (2012). Modeling the cellular uptake of magnetofluorescent nanoparticles in pancreatic cancer cells: a quantitative structure activity relationship study. Industrial & Engineering Chemistry Research, 51(32), 10712-10718
Open this publication in new window or tab >>Modeling the cellular uptake of magnetofluorescent nanoparticles in pancreatic cancer cells: a quantitative structure activity relationship study
2012 (English)In: Industrial & Engineering Chemistry Research, ISSN 0888-5885, E-ISSN 1520-5045, Vol. 51, no 32, p. 10712-10718Article in journal (Refereed) Published
Abstract [en]

An artificial neural network was employed to predict the cellular uptake of 109 magnetofluorescent nanoparticles (NPs) in pancreatic cancer cells on the basis of quantitative structure activity relationship method. Six descriptors chosen by combining self organizing map and stepwise multiple linear regression (MLR) techniques were used to correlate the nanostructure of the studied particles with their bioactivity using MLR and multilayered perceptron neural network (MLP-NN) modeling techniques. For the MLR and MLP-NN models, the correlation coefficient was 0.769 and 0.934, and the root-mean-square error was 0.364 and 0.150, respectively. The results obtained after a leave-many-out cross-validation test revealed the credibility of MLP-NN for the prediction of cellular uptake of NPs. In addition, sensitivity analysis of MLP-NN model indicated that the number of hydrogen-bond donor sites in the organic coating of a NP is the predominant factor responsible for cellular uptake.

National Category
Chemical Engineering
Identifiers
urn:nbn:se:umu:diva-59522 (URN)10.1021/ie3006947 (DOI)000307488400021 ()
Available from: 2012-09-17 Created: 2012-09-17 Last updated: 2018-06-08Bibliographically approved
Gouveia-Figueira, S., Karimpour, M., Bosson, J., Pourazar, J., Blomberg, A., Unosson, J., . . . Nording, M. L.Effect of controlled exposure to biodiesel exhaust on human plasma bioactive lipid profiles.
Open this publication in new window or tab >>Effect of controlled exposure to biodiesel exhaust on human plasma bioactive lipid profiles
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(English)Manuscript (preprint) (Other academic)
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:umu:diva-121147 (URN)
Available from: 2016-05-27 Created: 2016-05-27 Last updated: 2018-06-07
Gouveia-Figueira, S., Karimpour, M., Bosson, J., Blomberg, A., Unosson, J., Pourazar, J., . . . Nording, M. L.Mass spectrometry profiling of oxylipins, endocannabinoids and N-acylethanolamines in human lung lavage fluids reveal responsiveness of prostaglandin E2 and associated lipid metabolites to biodiesel exhaust exposure.
Open this publication in new window or tab >>Mass spectrometry profiling of oxylipins, endocannabinoids and N-acylethanolamines in human lung lavage fluids reveal responsiveness of prostaglandin E2 and associated lipid metabolites to biodiesel exhaust exposure
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(English)Manuscript (preprint) (Other academic)
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:umu:diva-121146 (URN)
Available from: 2016-05-27 Created: 2016-05-27 Last updated: 2018-06-07
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