N-Acetyl Functions and Acetate Detected by Nuclear Magnetic Resonance Spectroscopy of Urine to Detect Renal Dysfunction following Aminoglycoside and/or Glycopeptide Antibiotic Therapy

Racine, Stéphane; Toumelin, Philippe Le; Adnet, Frédéric; Cohen, Yves; Cupa, M; Hantz, Edith; Moyec, Laurence Le

doi:10.1159/000079179

Cited by 11 publications

(6 citation statements)

References 35 publications

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“…To examine the impact of ISO, resveratrol, or other resveratrol analogs on obesity and other metabolic disorders, a special diet, e.g., fat-rich diet should be tested for a longer period. Besides obesity, elevation of glycyl-glycine, N -acetyl-glycine, N -acetyl-glutamine, and N -acetyl-orthinine in body tissue/fluids has been observed in a variety of pathological conditions ( Racine et al, 2004 ; Carrola et al, 2011 ; Manna et al, 2011 ; Ouyang, 2012 ; Kim et al, 2013 ; Li et al, 2016 ; Schnackenberg et al, 2016 ). Therefore, downregulation of these biomarkers by IOS may provide health-promoting effects.…”

Section: Resultsmentioning

confidence: 99%

Pre-clinical Pharmacokinetic and Metabolomic Analyses of Isorhapontigenin, a Dietary Resveratrol Derivative

et al. 2018

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Background: Isorhapontigenin (trans–3,5,4′-trihydroxy–3′–methoxystilbene, ISO), a dietary resveratrol (trans–3,5,4′–trihydroxystilbene) derivative, possesses various health-promoting activities. To further evaluate its medicinal potentials, the pharmacokinetic and metabolomic profiles of ISO were examined in Sprague-Dawley rats.Methods: The plasma pharmacokinetics and metabolomics were monitored by liquid chromatography–tandem mass spectrometry (LC–MS/MS) and gas chromatography–tandem mass spectrometry (GC–MS/MS), respectively.Results: Upon intravenous injection (90 μmol/kg), ISO exhibited a fairly rapid clearance (CL) and short mean residence time (MRT). After a single oral administration (100 μmol/kg), ISO was rapidly absorbed and showed a long residence in the systemic circulation. Dose escalation to 200 μmol/kg resulted in higher dose-normalized maximal plasma concentrations (Cmax/Dose), dose-normalized plasma exposures (AUC/Dose), and oral bioavailability (F). One-week repeated daily dosing of ISO did not alter its major oral pharmacokinetic parameters. Pharmacokinetic comparisons clearly indicated that ISO displayed pharmacokinetic profiles superior to resveratrol as its Cmax/Dose, AUC/Dose, and F were approximately two to three folds greater than resveratrol. Metabolomic investigation revealed that 1-week ISO administration significantly reduced plasma concentrations of arachidonic acid, cholesterol, fructose, allantoin, and cadaverine but increased tryptamine levels, indicating its impact on metabolic pathways related to health-promoting effects.Conclusion: ISO displayed favorable pharmacokinetic profiles and may be a promising nutraceutical in view of its health-promoting properties.

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Section: Resultsmentioning

confidence: 99%

Pre-clinical Pharmacokinetic and Metabolomic Analyses of Isorhapontigenin, a Dietary Resveratrol Derivative

et al. 2018

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“…In humans, elevation of these molecules in urine has also been reported and linked to renal tubular injury after antibiotic treatment (Racine et al, 2004), or a mutation in the aminoacylase I (EC3.5.1.14, a renal cortex enzyme which hydrolyses N-acetylated amino acids) gene (Gerlo et al, 2006). Our observations may suggest that alcohol treatment may inhibit aminoacylase I and that urinary n-acetylglutamine and n-acetlylglycine could be considered as potential non-invasive biomarkers for alcohol consumption.…”

Section: Discussionmentioning

confidence: 99%

Metabolomic profiling of a modified alcohol liquid diet model for liver injury in the mouse uncovers new markers of disease

Bradford

O’Connell

Han

et al. 2008

Toxicology and Applied Pharmacology

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Metabolomic evaluation of urine and liver was conducted to assess the biochemical changes that occur as a result of alcohol-induced liver injury. Male C57BL/6J mice were fed an isocaloric control-or alcohol-containing liquid diet with 35% of calories from corn oil, 18% protein and 47% carbohydrate/alcohol for up to 36 days ad libitum. Alcohol treatment was initiated at 7 g/kg/day and gradually reached a final dose of 21 g/kg/day. Urine samples were collected at 22, 30 and 36 days and in additional treatment groups, liver and serum samples were harvested at 28 days. Steatohepatitis was induced in the alcohol-fed group since a 5-fold increase in serum alanine aminotransferase activity, a 6-fold increase in liver injury score (necrosis, inflammation and steatosis) and an increase in lipid peroxidation in liver were observed. Liver and urine samples were analyzed by nuclear magnetic resonance spectroscopy and electrospray infusion/Fourier transform ion cyclotron resonance-mass spectrometry. In livers of alcohol-treated mice the following changes were noted. Hypoxia and glycolysis were activated as evidenced by elevated levels of alanine and lactate. Tyrosine, which is required for L-DOPA and dopamine as well as thyroid hormones, was elevated possibly reflecting alterations of basal metabolism by alcohol. A 4-fold increase in the prostacyclin inhibitor 7,10,13,16-docosatetraenoic acid, a molecule important for regulation of platelet formation and blood clotting, may explain why chronic drinking causes serious bleeding problems. Metabolomic analysis of the urine revealed that alcohol treatment leads to decreased excretion of taurine, a metabolite of glutathione, and an increase in lactate, n-acetylglutamine and n-acetylglycine. Changes in the latter two metabolites suggest an inhibition of the kidney enzyme aminoacylase I and may be useful as markers for alcohol consumption.

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“…N-acetylglutamine is a kind of amino acid derivative (an acetylated analogue of glutamine) [41]. In this study, compared with the control group, the relative level of N-acetylglutamine was elevated significantly following OP treatment at 1 μg/kg/day (Figure 6).…”

Section: Resultsmentioning

confidence: 61%

Metabolomics Reveals Metabolic Changes Caused by Low-Dose 4-Tert-Octylphenol in Mice Liver

Zhou

Ding

Yang

et al. 2018

IJERPH

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Background: Humans are constantly exposed to low concentrations of 4-tert-octylphenol (OP). However, studies investigating the effects of low-dose OP on the liver are scarce, and the mechanism of these effects has not been thoroughly elucidated to date. Methods: Adult male institute of cancer research (ICR) mice were exposed to low-dose OP (0, 0.01 and 1 μg/kg/day) for 7 consecutive days. Weights of mice were recorded daily during the experiment. Blood serum levels of OP, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined, and haematoxylin-eosin (HE) staining of the liver was performed. We applied an integrated metabolomic and enzyme gene expression analysis to investigate liver metabolic changes, and the gene expression of related metabolic enzymes was determined by real-time PCR and ELISA. Results: OP in blood serum was increased after OP exposure, while body weights of mice were unchanged. Liver weight and its organ coefficient were decreased significantly in the OP (1 μg/kg/day) group, but ALT and AST, as well as the HE staining results, were unchanged after OP treatment. The levels of cytidine, uridine, purine and N-acetylglutamine were increased significantly, and the level of vitamin B6 was decreased significantly in mice treated with OP (1 μg/kg/day). The mRNA and protein levels of Cda and Shmt1 were both increased significantly in OP (1 μg/kg/day)-treated mice. Conclusions: Through metabolomic analysis, our study firstly found that pyrimidine and purine synthesis were promoted and that N-acetylglutamine was upregulated after low-dose OP treatment, indicating that the treatment disturbed nucleic acid and amino acid metabolism in mice liver.

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N-Acetyl Functions and Acetate Detected by Nuclear Magnetic Resonance Spectroscopy of Urine to Detect Renal Dysfunction following Aminoglycoside and/or Glycopeptide Antibiotic Therapy

Cited by 11 publications

References 35 publications

Pre-clinical Pharmacokinetic and Metabolomic Analyses of Isorhapontigenin, a Dietary Resveratrol Derivative

Pre-clinical Pharmacokinetic and Metabolomic Analyses of Isorhapontigenin, a Dietary Resveratrol Derivative

Metabolomic profiling of a modified alcohol liquid diet model for liver injury in the mouse uncovers new markers of disease

Metabolomics Reveals Metabolic Changes Caused by Low-Dose 4-Tert-Octylphenol in Mice Liver

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