scholarly journals Metabolic and Lipidomic Assessment of Kidney Cells Exposed to Nephrotoxic Vancomycin Dosages

2021 ◽  
Vol 22 (18) ◽  
pp. 10111
Author(s):  
Simon Lagies ◽  
Roman Pichler ◽  
Georg Vladimirov ◽  
Jana Gawron ◽  
Fabian Bäzner ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Cell Lines ◽  
Plasma Concentrations ◽  
Gas Chromatography Mass Spectrometry ◽  
Resistant Bacteria ◽  
Kidney Cells ◽  
Renal Epithelial Cell ◽  
Gram Positive Bacteria ◽  
Chromatography Mass Spectrometry ◽  
Lactate Levels

Vancomycin is a glycopeptide antibiotic used against multi-drug resistant gram-positive bacteria such as Staphylococcus aureus (MRSA). Although invaluable against resistant bacteria, vancomycin harbors adverse drug reactions including cytopenia, ototoxicity, as well as nephrotoxicity. Since nephrotoxicity is a rarely occurring side effect, its mechanism is incompletely understood. Only recently, the actual clinically relevant concentration the in kidneys of patients receiving vancomycin was investigated and were found to exceed plasma concentrations by far. We applied these clinically relevant vancomycin concentrations to murine and canine renal epithelial cell lines and assessed metabolic and lipidomic alterations by untargeted and targeted gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry analyses. Despite marked differences in the lipidome, both cell lines increased anabolic glucose reactions, resulting in higher sorbitol and lactate levels. To the best of our knowledge, this is the first endometabolic profiling of kidney cells exposed to clinically relevant vancomycin concentrations. The presented study will provide a valuable dataset to nephrotoxicity researchers and might add to unveiling the nephrotoxic mechanism of vancomycin.

scholarly journals Anti-Tumour Effect of two Persicaria Species Seeds on Colon and Prostate Cancers

2018 ◽  
Vol 11 (2) ◽  
pp. 635-644
Author(s):  
Ahmed Mohamed Mohamed Youssef ◽  
Zeinab Ahmed Said El-Swaify
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Cell Lines ◽  
Human Cancer ◽  
Gas Chromatography Mass Spectrometry ◽  
Active Constituents ◽  
Aerial Parts ◽  
Anti Tumour Activity ◽  
Chromatography Mass Spectrometry ◽  
Tumour Activity

The active constituents present in Persicaria salicifolia and Persicaria senegalensis seeds may possess anti-tumour activity. Therefore, P. salicifolia and P. senegalensis seeds were extracted and analysed to identify their active constituents. Phytochemical compounds exist in 50 % methanol extracts of P. salicifolia and P. senegalensis seeds were identified through High-Performance Liquid Chromatography (HPLC), Liquid Chromatography/ Mass Spectrometry (LC/MS), and Gas Chromatography-Mass Spectrometry (GC/MS). MTT assay was utilized to analyse the anti-tumour activity of P. salicifolia and P. senegalensis seeds compared to their aerial parts against CaCo-2 and PC3 cell lines. The constituents of Persicaria species seeds have phenolic acids, flavonoid, and lipid compounds. The cytotoxicity of aerial parts of P. salicifolia showed half maximal inhibitory concentration (IC50) of 1.1 ± 0.15 µg/ml and 0.5 ± 0.0011 µg/ml and the seeds were 0.6 ± 0.0018 µg/ml and 1.0 ± 0.009 µg/ml against PC3 and CaCO-2 cell lines, respectively. While, the aerial parts of P. senegalensis showed IC50 of 2.3 ± 0.03 µg/ml and 2.0 ± 0.03 µg/ml, and the seeds were 3.5 ± 0.06 µg/ml and 1.5 ± 0.03 µg/ml against PC3 and Caco-2, respectively. The results showed that there was a potential cytotoxicity of two Persicaria species seeds against two human cancer cell lines comparing to their aerial parts that have antitumor activity as it is confirmed by the literature.

scholarly journals Hormonal diagnosis of 21-hydroxylase deficiency in plasma and urine of neonates using benchtop gas chromatography-mass spectrometry

2000 ◽  
Vol 165 (3) ◽  
pp. 679-683 ◽  
Author(s):  
SA Wudy ◽  
M Hartmann ◽  
J Homoki
Keyword(s):  
Mass Spectrometry ◽  
Gas Chromatography ◽  
Cord Blood ◽  
Plasma Concentrations ◽  
Gas Chromatography Mass Spectrometry ◽  
Confirmatory Test ◽  
Hydroxylase Deficiency ◽  
Chromatography Mass Spectrometry ◽  
Steroid Profiling ◽  
21 Hydroxylase Deficiency

We aimed at measuring the first plasma concentrations of 17-hydroxyprogesterone (17OH-P) determined by benchtop isotope dilution/gas chromatography-mass spectrometry (ID/GC-MS) in term neonates with or without 21-hydroxylase deficiency. Plasma samples from normal cord blood specimens (n=30), unaffected neonates (n=38) and neonatal patients with classical 21-hydroxylase deficiency (eight salt-wasters, three simple virilizers) were analyzed. Steroid profiling of random urinary specimens by GC-MS served as a confirmatory test for 21-hydroxylase deficiency. 17OH-P (nmol/l) in cord blood plasma lay between 11.66 and 75.92 (median 24.74). It declined shortly after birth. In the first 8 days of life, the time that screening for 21-hydroxylase deficiency is performed, 17OH-P ranged between undetected levels and an upper limit of 22.87 (median 4.11). Thereafter (days 9-28) its concentrations lay between 2.18 and 20.30 (median 6.22). Except one simple virilizer, all other patients with 21-hydroxylase deficiency had clearly elevated plasma 17OH-P at the time that screening for 21-hydroxylase deficiency would be performed. We suggest ID/GC-MS, which provides the highest specificity in steroid analysis, for checking suspicious concentrations of 17OH-P in neonates and underscore the potential of urinary steroid profiling by GC-MS as a rapid, non-invasive and non-selective confirmatory test for congenital adrenal hyperplasia.

scholarly journals A study of in vitro metabolism and cytotoxicity of mephedrone and methoxetamine in human and pig liver models using GC/MS and LC/MS analyses

2020 ◽  
Vol 18 (1) ◽  
pp. 1507-1522
Author(s):  
Majed Alshamaileh ◽  
Issam Hussain ◽  
Mark Baron ◽  
Ruth Croxton ◽  
Marleen Vetter ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Cell Death ◽  
Cell Lines ◽  
Liver Microsomes ◽  
Gas Chromatography Mass Spectrometry ◽  
Cytotoxic Effects ◽  
Pig Liver ◽  
Chromatography Mass Spectrometry ◽  
Optimized Conditions

AbstractIn the current study, the metabolism of two novel psychoactive substances (NPSs), mephedrone and methoxetamine (MXE), was studied in vitro in pig liver microsomes to determine potential metabolites by liquid chromatography-mass spectrometry (LC-MS). Later, in vitro studies were performed using HepaRG™ cells to determine the human metabolites of these drugs using gas chromatography-mass spectrometry (GC-MS). The aim of the study was to detect metabolites from the metabolic mixture in the human cell lines using GC-MS, since this is a more readily available technique within forensic laboratories. Microsomes were prepared through a conventional ultracentrifugation method and incubated under optimized conditions with the drugs for 3 h. Subsequently, the samples were investigated using LC-MS. A similar methodology was then applied in the HepaRG™ cells, and the GC-MS conditions were optimized using N,O-bis(trimethylsilyl)trifluoroacetamide as a derivatization agent. The analysis showed two molecules from a successful in vitro metabolism, namely, hydroxytoly-mephedrone and nor-dihydro mephedrone. For MXE, two metabolites are presented produced by the O-demethylation and reduction of the ketone moiety to the corresponding alcohol, respectively. Using the human HepaRG™ cells, only nor-dihydro mephedrone could be identified by GC-MS. Since hydroxytoly-mephedrone and the MXE metabolites are more polar, it is suggested that GC-MS even with derivatization may not be suitable. In addition, cytotoxicity was studied utilizing HepaRG™ cell lines. The drugs show cytotoxic effects causing in vitro cell death, within the specified range of EC50 0.3211 mM (79 μg/mL) and 0.6297 mM (111 μg/mL) for mephedrone and MXE, respectively. These drugs were able to cause 73–84% cell death.

scholarly journals Determination of Muscone in Rats Plasma following Oral Administration of Artificial Musk: Using of Combined Headspace Gas Chromatography-Mass Spectrometry

2014 ◽  
Vol 2014 ◽  
pp. 1-5
Author(s):  
Qibiao Wu ◽  
Haitao Li ◽  
Yujing Leng ◽  
Haishan Deng ◽  
Haibo Cheng ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Gas Chromatography ◽  
Oral Administration ◽  
Plasma Concentrations ◽  
High Sensitivity ◽  
Pharmacokinetic Profile ◽  
Gas Chromatography Mass Spectrometry ◽  
Minimum Detectable Concentration ◽  
Chromatography Mass Spectrometry

To develop an analytical method for determination of plasma concentrations of muscone in rats following oral administration of artificial musk, with the aim of investigating the pharmacokinetic profile of artificial musk. Plasma samples were pretreated with acetonitrile to precipitate proteins. Headspace injection coupled with gas chromatography-mass spectrometry was used for quantitative analysis of muscone concentrations. A strong linear relationship was obtained for plasma muscone concentrations ranging from 75.6 to 7560 ng·mL−1  R2=0.9998, with the minimum detectable concentration being 25 ng·mL−1. The within-day and interday precision for determination of three different concentrations of muscone were favorable (RSD < 25%). The average absolute recovery ranged from 83.7 to 88.6%, with an average relative recovery of 100.5 to 109.8%. The method described was characterized by stability and reliability, and in the present study showed significant specificity and high sensitivity. This method would be applicable to the analysis of plasma concentrations of muscone in preclinical contexts, where artificial musk is used.

Volatile metabolomic signature of bladder cancer cell lines based on gas chromatography–mass spectrometry

Metabolomics ◽  
2018 ◽  
Vol 14 (5) ◽  
Author(s):  
Daniela Rodrigues ◽  
Joana Pinto ◽  
Ana Margarida Araújo ◽  
Sara Monteiro-Reis ◽  
Carmen Jerónimo ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Gas Chromatography ◽  
Bladder Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Bladder Cancer Cell ◽  
Gas Chromatography Mass Spectrometry ◽  
Chromatography Mass Spectrometry

scholarly journals Thin Layer Chromatography-Bioautography and Gas Chromatography-Mass Spectrometry of Antimicrobial Leaf Extracts from PhilippinePiper betleL. against Multidrug-Resistant Bacteria

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Demetrio L. Valle ◽  
Juliana Janet M. Puzon ◽  
Esperanza C. Cabrera ◽  
Windell L. Rivera
Keyword(s):  
Mass Spectrometry ◽  
Gas Chromatography ◽  
Thin Layer ◽  
Thin Layer Chromatography ◽  
Multidrug Resistant ◽  
Gas Chromatography Mass Spectrometry ◽  
Resistant Bacteria ◽  
Chromatography Mass Spectrometry ◽  
Ethanol Extracts ◽  
Layer Chromatography

This study isolated and identified the antimicrobial compounds of PhilippinePiper betleL. leaf ethanol extracts by thin layer chromatography- (TLC-) bioautography and gas chromatography-mass spectrometry (GC-MS). Initially, TLC separation of the leaf ethanol extracts provided a maximum of eight compounds withRfvalues of 0.92, 0.86, 0.76, 0.53, 0.40, 0.25, 0.13, and 0.013, best visualized when inspected under UV 366 nm. Agar-overlay bioautography of the isolated compounds demonstrated two spots withRfvalues of 0.86 and 0.13 showing inhibitory activities against two Gram-positive multidrug-resistant (MDR) bacteria, namely, methicillin-resistantStaphylococcus aureusand vancomycin-resistantEnterococcus. The compound with anRfvalue of 0.86 also possessed inhibitory activity against Gram-negative MDR bacteria, namely, carbapenem-resistant Enterobacteriaceae-Klebsiella pneumoniaeand metallo-β-lactamase-producingAcinetobacter baumannii. GC-MS was performed to identify the semivolatile and volatile compounds present in the leaf ethanol extracts. Six compounds were identified, four of which are new compounds that have not been mentioned in the medical literature. The chemical compounds isolated include ethyl diazoacetate, tris(trifluoromethyl)phosphine, heptafluorobutyrate, 3-fluoro-2-propynenitrite, 4-(2-propenyl)phenol, and eugenol. The results of this study could lead to the development of novel therapeutic agents capable of dealing with specific diseases that either have weakened reaction or are currently not responsive to existing drugs.

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