Two-dimensional proton nuclear magnetic resonance "maps" of acetaminophen metabolites in human urine.

Bales, John; Nicholson, J. K.; Sadler, Peter J.

doi:10.1093/clinchem/31.5.757

Cited by 89 publications

(36 citation statements)

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“…Paracetamol (abbreviated as APAP, IUPAC name N -(4-hydroxyphenyl)ethanamide, acetaminophen, 4-acetaminophenol, 4′-hydroxyacetanilide, N -acetyl- p -aminophenol), is currently one of the most widely used over-the-counter available antiphlogistic drug worldwide (Wu et al 2012 ; Rhee et al 2013 ). Chemically, paracetamol consists of a benzene ring core substituted by one hydroxyl group and the nitrogen atom of an amide group at the (1,4) para position (Bales et al 1985 ; Wu et al 2012 ). In the UK, paracetamol is classified in the top three of the most frequently prescribed drugs.…”

Section: Monocyclic Nonsteroidal Anti-inflammatory Drugsmentioning

confidence: 99%

Organic micropollutants paracetamol and ibuprofen—toxicity, biodegradation, and genetic background of their utilization by bacteria

Żur

Piński

Marchlewicz

et al. 2018

Environ Sci Pollut Res

199

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Currently, analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs) are classified as one of the most emerging group of xenobiotics and have been detected in various natural matrices. Among them, monocyclic paracetamol and ibuprofen, widely used to treat mild and moderate pain are the most popular. Since long-term adverse effects of these xenobiotics and their biological and pharmacokinetic activity especially at environmentally relevant concentrations are better understood, degradation of such contaminants has become a major concern. Moreover, to date, conventional wastewater treatment plants (WWTPs) are not fully adapted to remove that kind of micropollutants. Bioremediation processes, which utilize bacterial strains with increased degradation abilities, seem to be a promising alternative to the chemical methods used so far. Nevertheless, despite the wide prevalence of paracetamol and ibuprofen in the environment, toxicity and mechanism of their microbial degradation as well as genetic background of these processes remain not fully characterized. In this review, we described the current state of knowledge about toxicity and biodegradation mechanisms of paracetamol and ibuprofen and provided bioinformatics analysis concerning the genetic bases of these xenobiotics decomposition.

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Section: Monocyclic Nonsteroidal Anti-inflammatory Drugsmentioning

confidence: 99%

Organic micropollutants paracetamol and ibuprofen—toxicity, biodegradation, and genetic background of their utilization by bacteria

Żur

Piński

Marchlewicz

et al. 2018

Environ Sci Pollut Res

199

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show abstract

“…Recently, omics technologies have been utilized to analyze APAP-induced hepatotoxicity, including proton nuclear magnetic resonance profiling of APAP metabolites in hu-man urine [19][20][21], genomic profiling of mouse liver specific to APAP toxicity [22], 2DE analysis of protein targets of APAP reactive metabolites in mouse liver [23,24], and overall proteomic profiling of APAP-induced hepatotoxicity in rat and mouse livers [25][26][27][28]. Due to technical limitations of the techniques used in these studies (e.g., 2D-GE), they did not provide sufficient information for full understanding of the molecular changes under APAP-induced hepatotoxicity.…”

Section: Clinical Relevancementioning

confidence: 99%

Proteomic analysis of acetaminophen-induced hepatotoxicity and identification of heme oxygenase 1 as a potential plasma biomarker of liver injury

et al. 2016

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Purpose Overdose of acetaminophen (APAP) is a major cause of acute liver failure. This study was aimed to identify pathways related to hepatotoxicity and potential biomarkers of liver injury. Experimental design Rats were treated with low (100 mg/kg) and high (1250 mg/kg) doses of APAP, and liver tissues at 6 and 24 h post-treatment were analyzed using a proteomic approach of 16O/18O labeling and 2D-LC-MS/MS. Results Molecular pathways evolved progressively from scattered and less significant perturbations to more focused and significant alterations in a dose- and time-dependent manner upon APAP treatment. Imbalanced expression of hemeoxygenase 1 (HMOX1) and biliverdin reductase A (BLVRA) was associated with hepatotoxicity. Protein abundance changes of a total of 31 proteins were uniquely correlated to liver damage, among which a dramatic increase of HMOX1 levels in plasma was observed. Liver injury-associated significant elevation of plasma HMOX1 was further validated in mice treated with APAP. Conclusions and clinical relevance This study unveiled molecular changes associated with APAP-induced liver toxicity at the pathway levels and identified HMOX1 as a potential plasma biomarker of liver injury.

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“…7 It has a plasma half-life of around 2 h. 8 Paracetamol, as shown in figure 1(a), consists of a benzene ring core, substituted by one hydroxyl group and the nitrogen atom of an amide group in the Para (1, 4) pattern. 9 It has a pK a value of 9.5 and is therefore largely unionized over the physiological range of pH. 10 It was proposed that Paracetamol exerted its analgesic action by inhibition of centrally situated isoforms of the cyclooxygenase enzyme.…”

Section: Introductionmentioning

confidence: 99%

Molecular dynamics simulations and free energy profile of Paracetamol in DPPC and DMPC lipid bilayers

et al. 2014

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Molecular dynamics (MD) simulations and biased MD simulation were carried out for the neutral form of Paracetamol inserted in fully hydrated dipalmitoylphosphatidylcholine (DPPC) and dimyristoylphosphatidylcholine (DMPC) lipid bilayers. For comparison, fully hydrated DMPC and DPPC lipid bilayers were also simulated separately without Paracetamol. The simulation time for each system was 50 ns. At two concentrations of Paracetamol, various properties of the lipid bilayer such as area per lipid, order parameter, diffusion coefficient, radial distribution function, electrostatic potential, mass density and hydrogen bonds have been calculated. Also, the convergence in time of the free energy profile of the Paracetamol along a DPPC bilayer normal was calculated by umbrella sampling method. From the obtained results, it can be concluded that neutral form of Paracetamol shows a generally similar behaviour in DPPC and DMPC lipid bilayers. It was shown that the addition of Paracetamol causes a decrease in tail order parameter of both DPPC and DMPC lipid bilayers and the tail of Paracetamol adopts an inward orientation in the lipid bilayers. Also from the free energy profile, the high penetration barrier in the bilayer centre was determined.

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Two-dimensional proton nuclear magnetic resonance "maps" of acetaminophen metabolites in human urine.

Cited by 89 publications

References 0 publications

Organic micropollutants paracetamol and ibuprofen—toxicity, biodegradation, and genetic background of their utilization by bacteria

Organic micropollutants paracetamol and ibuprofen—toxicity, biodegradation, and genetic background of their utilization by bacteria

Proteomic analysis of acetaminophen-induced hepatotoxicity and identification of heme oxygenase 1 as a potential plasma biomarker of liver injury

Molecular dynamics simulations and free energy profile of Paracetamol in DPPC and DMPC lipid bilayers

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