scholarly journals Short Report: Using Targeted Urine Metabolomics to Distinguish Between Manganese Exposed and Unexposed Workers in a Small Occupational Cohort

2021 ◽  
Vol 9 ◽  
Author(s):  
Kayla A. Carter ◽  
Christopher D. Simpson ◽  
Daniel Raftery ◽  
Marissa G. Baker

Objectives: Despite the widespread use of manganese (Mn) in industrial settings and its association with adverse neurological outcomes, a validated and reliable biomarker for Mn exposure is still elusive. Here, we utilize targeted metabolomics to investigate metabolic differences between Mn-exposed and -unexposed workers, which could inform a putative biomarker for Mn and lead to increased understanding of Mn toxicity.Methods: End of shift spot urine samples collected from Mn exposed (n = 17) and unexposed (n = 15) workers underwent a targeted assay of 362 metabolites using LC-MS/MS; 224 were quantified and retained for analysis. Differences in metabolite abundances between exposed and unexposed workers were tested with a Benjamini-Hochberg adjusted Wilcoxon Rank-Sum test. We explored perturbed pathways related to exposure using a pathway analysis.Results: Seven metabolites were significantly differentially abundant between exposed and unexposed workers (FDR ≤ 0.1), including n-isobutyrylglycine, cholic acid, anserine, beta-alanine, methionine, n-isovalerylglycine, and threonine. Three pathways were significantly perturbed in exposed workers and had an impact score >0.5: beta-alanine metabolism, histidine metabolism, and glycine, serine, and threonine metabolism.Conclusion: This is one of few studies utilizing targeted metabolomics to explore differences between Mn-exposed and -unexposed workers. Metabolite and pathway analysis showed amino acid metabolism was perturbed in these Mn-exposed workers. Amino acids have also been shown to be perturbed in other occupational cohorts exposed to Mn. Additional research is needed to characterize the biological importance of amino acids in the Mn exposure-disease continuum, and to determine how to appropriately utilize and interpret metabolomics data collected from occupational cohorts.

Metabolomics ◽  
2014 ◽  
Vol 11 (3) ◽  
pp. 764-777 ◽  
Author(s):  
Alexander Kaever ◽  
Manuel Landesfeind ◽  
Kirstin Feussner ◽  
Alina Mosblech ◽  
Ingo Heilmann ◽  
...  

1964 ◽  
Vol 11 (01) ◽  
pp. 064-074 ◽  
Author(s):  
Robert H Wagner ◽  
William D McLester ◽  
Marion Smith ◽  
K. M Brinkhous

Summary1. The use of several amino acids, glycine, alpha-aminobutyric acid, alanine, beta-alanine, and gamma-aminobutyric acid, as plasma protein precipitants is described.2. A specific procedure is detailed for the preparation of canine antihemophilic factor (AHF, Factor VIII) in which glycine, beta-alanine, and gammaaminobutyric acid serve as the protein precipitants.3. Preliminary results are reported for the precipitation of bovine and human AHF with amino acids.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Aragon Herrera ◽  
S Feijoo-Bandin ◽  
M Otero Santiago ◽  
S Moranha Fernandez ◽  
L Anido Varela ◽  
...  

Abstract Background Empagliflozin is a potent, highly selective sodium glucose cotransporter-2 (SGLT2) inhibitor used as an effective and well-tolerated antihyperglycaemic agent. Beyond lowering glucose, empagliflozin exerts a favorable effect on a number of nonglycaemic outcomes, including modest reductions in bodyweight and blood pressure, and it has cardioprotective and renoprotective properties in patients with T2D and established cardiovascular disease (EMPA-REG OUTCOME). Purpose Since liver fat content represents a risk factor for cardiovascular diseases, and empagliflozin has been recently suggested to be able to contribute to the early treatment of nonalcoholic fatty liver disease in T2D, we aimed to study the effect of the empagliflozin treatment in the liver metabolome of type 2 diabetic rats. Methods Male ZDF-Leprfa/fa rats were treated with 30 mg/kg/d of empagliflozin p.o for six weeks. Metabolic profiling of the hepatic tissue was analyzed using UHPLC-MS based platforms. We performed a hematoxylin/eosin staining to determine the tissue integrity and liver fat accumulation, and a Masson's trichrome staining to analyze liver fibrosis. All animals were maintained and euthanized following protocols approved by the Animal Care Committee of the University of Santiago de Compostela in accordance with European Union Directive 2010/63. Results Empaglifozin treatment reduced blood glucose levels to normal (128.2±6.51 mg/dL), while untreated control rats showed high glucose levels (404.3±17.49 mg/dL). Hepatic histological analysis did not show differences regarding neither fat accumulation nor fibrosis between empagliflozin treated and control rats. Circulating levels of cholesterol, HDL, LDL, GTP, GGT triglycerides remained unaltered after empaglifozin treatment vs. control. 384 metabolites were analyzed in the liver tissue samples, observing significantly increased levels of 10 types of glycerolipids, 24 phosphatidylcholines, 8 amino acids, 1 polyunsaturated fatty acid, 4 lysophosphatidylethanolamines, 7 lysophosphatidylinositols, 1 carboxylic acid and 1 nucleoside in the empagliflozin treated rats with respect to the control group. In addition, treatment with empagliflozin produced a significant decrease of 1 glycerolipid, 1 phosphatidylcholine, 1 bile acid, 1 nucleoside and the NAD oxidoreduction coenzyme. Conclusions We demonstrated that empagliflozin significantly modify the liver content of the different lipid species, with the most relevant altered metabolic classes belonging to glycerophospholipids, especially monoacyl-species, and aromatic amino acids. Considering the suggested potential beneficial effect of the treatment with empagliflozin in the prevention of liver fibrosis, our metabolomics data can help to evaluate the impact and the mechanism of action of SGLT2 inhibitors at hepatic level. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Boehringer Ingelheim


2020 ◽  
Vol 36 (12) ◽  
pp. 3913-3915
Author(s):  
Hemi Luan ◽  
Xingen Jiang ◽  
Fenfen Ji ◽  
Zhangzhang Lan ◽  
Zongwei Cai ◽  
...  

Abstract Motivation Liquid chromatography–mass spectrometry-based non-targeted metabolomics is routinely performed to qualitatively and quantitatively analyze a tremendous amount of metabolite signals in complex biological samples. However, false-positive peaks in the datasets are commonly detected as metabolite signals by using many popular software, resulting in non-reliable measurement. Results To reduce false-positive calling, we developed an interactive web tool, termed CPVA, for visualization and accurate annotation of the detected peaks in non-targeted metabolomics data. We used a chromatogram-centric strategy to unfold the characteristics of chromatographic peaks through visualization of peak morphology metrics, with additional functions to annotate adducts, isotopes and contaminants. CPVA is a free, user-friendly tool to help users to identify peak background noises and contaminants, resulting in decrease of false-positive or redundant peak calling, thereby improving the data quality of non-targeted metabolomics studies. Availability and implementation The CPVA is freely available at http://cpva.eastus.cloudapp.azure.com. Source code and installation instructions are available on GitHub: https://github.com/13479776/cpva. Supplementary information Supplementary data are available at Bioinformatics online.


2012 ◽  
Vol 9 (1) ◽  
pp. 28 ◽  
Author(s):  
Brandon D Spradley ◽  
Kristy R Crowley ◽  
Chih-Yin Tai ◽  
Kristina L Kendall ◽  
David H Fukuda ◽  
...  

1973 ◽  
Vol 4 (44) ◽  
pp. no-no
Author(s):  
V. T. BRAICHENKO ◽  
Z. F. SOLOMKO ◽  
M. S. MALINOVSKII ◽  
R. F. RED'KO
Keyword(s):  

Metabolites ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 114 ◽  
Author(s):  
Vuanghao Lim ◽  
Sara Ghorbani Gorji ◽  
Venea Dara Daygon ◽  
Melissa Fitzgerald

Selected Australian native fruits such as Davidson’s plum, finger lime and native pepperberry have been reported to demonstrate potent antioxidant activity. However, comprehensive metabolite profiling of these fruits is limited, therefore the compounds responsible are unknown, and further, the compounds of nutritional value in these native fruits are yet to be described. In this study, untargeted and targeted metabolomics were conducted using the three fruits, together with assays to determine their antioxidant activities. The results demonstrate that targeted free and hydrolysed protein amino acids exhibited high amounts of essential amino acids. Similarly, important minerals like potassium were detected in the fruit samples. In antioxidant activity, Davidson’s plum reported the highest activity in ferric reducing power (FRAP), finger lime in antioxidant capacity (ABTS), and native pepperberry in free radical scavenging (DPPH) and phosphomolybdenum assay. The compounds responsible for the antioxidant activity were tentatively identified using untargeted GC×GC-TOFMS and UHPLC-QqQ-TOF-MS/MS metabolomics. A clear discrimination into three clusters of fruits was observed using principal component analysis (PCA) and partial least squares (PLS) analysis. The correlation study identified a number of compounds that provide the antioxidant activities. GC×GC-TOFMS detected potent aroma compounds of limonene, furfural, and 1-R-α-pinene. Based on the untargeted and targeted metabolomics, and antioxidant assays, the nutritional potential of these Australian bush fruits is considerable and supports these indigenous fruits in the nutraceutical industry as well as functional ingredients for the food industry, with such outcomes benefiting Indigenous Australian communities.


2020 ◽  
Vol 13 ◽  
pp. 251686572090405 ◽  
Author(s):  
Ami R Zota ◽  
Ruth J Geller ◽  
Brianna N VanNoy ◽  
Cherie Q Marfori ◽  
Sana Tabbara ◽  
...  

Phthalates are associated with multiple, adverse reproductive outcomes including increased risk of uterine leiomyoma (fibroids). Phthalates can interact with epigenetic modifications including microRNAs (miRNAs), which help regulate processes crucial to fibroid pathogenesis. However, no prior study has examined the influence of phthalates on miRNA expression in fibroid tumors. We conducted a preliminary, cross-sectional study to examine the associations between phthalate exposures and miRNA expression levels in fibroid tumors and to explore potential effect modification by race/ethnicity. We quantified expression levels of 754 miRNAs in fibroid tumor samples and analyzed spot urine samples for phthalate metabolites collected from 45 pre-menopausal women undergoing surgery for fibroid treatment at an academic hospital. Associations between miRNA levels in fibroids and phthalate biomarkers were evaluated using linear regression adjusting for age, race/ethnicity, and body mass index (BMI). Statistical tests were adjusted for multiple comparisons. We also performed in silico Ingenuity Pathway Analysis to identify the biological pathways that are regulated by phthalate-associated miRNAs. Mono-hydroxybutyl phthalate and mono(2-ethyl-5-hydroxyhexyl) phthalate were positively associated with miR-10a-5p (β = 0.76, 95% CI = [0.40, 1.11]) and miR-577 (β = 1.06, 95% CI = [0.53, 1.59]), respectively. A total of 8 phthalate-miRNA associations varied by race/ethnicity (qinteraction < 0.10). Pathway analysis revealed that mRNA gene targets of phthalate-associated miRNAs were significantly associated with multiple fibroid-related processes including angiogenesis, apoptosis, and proliferation of connective tissues. Collectively, these data suggest that exposures to some phthalates are associated with miRNA in fibroids, and that associations may vary by race/ethnicity. Validation of these findings may provide insight into mechanisms underlying associations between phthalates and fibroids and contribute to novel hypotheses regarding racial/ethnic disparities in fibroids.


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