Phenylacetic acid in human body fluids: high correlation between plasma and cerebrospinal fluid concentration values.

Sandler, M.; Ruthven, C.R.J.; Goodwin, B.L.; Lees, Andrew J.; Stern, Gerald

doi:10.1136/jnnp.45.4.366

Cited by 40 publications

(10 citation statements)

References 13 publications

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“…This may be attributed to LCMS analysis in previous studies compared to GCMS analysis used in this study. Phenyl acetic acid is non-polar in its non-conjugated form and has a low molecular weight [35]; therefore, it is better detected by the GCMS due to poor ionisation in the LCMS. An improved sensitivity of GCMS for the detection of PAA and PBA compared to low sensitivity of LCMS has been demonstrated in other studies [36,37,38].…”

Section: Discussionmentioning

confidence: 99%

Impact of Fermentable Fibres on the Colonic Microbiota Metabolism of Dietary Polyphenols Rutin and Quercetin

Mansoorian

Combet

Alkhaldy

et al. 2019

IJERPH

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Dietary fibre and polyphenols are both metabolised to short-chain fatty acids (SCFAs) and phenolic acids (PA) by the colonic microbiota. These may alter microbiota growth/diversity, but their interaction is not understood. Interactions between rutin and raftiline, ispaghula or pectin were investigated in human faecal batch cultures (healthy participants; 19–33 years, 4 males, 6 females, BMI 18.4–27.4) after a low (poly)phenol diet three days prior to study. Phenolic acids were measured by gas chromatography-mass spectrometry and SCFAs by gas chromatography-flame ionisation after 2, 4, 6, and 24 h. Rutin fermentation produced Phenyl acetic acid (PAA), 4-Hydroxy benzoic acid (4-OHBA), 3-Hydroxy phenyl acetic acid (3-OHPAA), 4-Hydroxy phenyl acetic acid (4-OHPAA), 3,4-Dihydroxy phenyl acetic acid (3,4-diOHPAA), 3-Hydroxy phenyl propionic acid (3-OHPPA), and 4-Hydroxy phenyl propionic acid (4-OHPPA). 3,4-DiOHPAA and 3-OHPAA were predominant at 6 h (1.9 ± 1.8 µg/mL, 2.9 ± 2.5 µg/mL, and 0.05 ± 0.0 µg/mL, respectively) and 24 h (5.5 ± 3.3 µg/mL, 3.1 ± 4.2 µg/mL, and 1.2 ± 1.6 µg/mL). Production of all PA except 3-OHPPA and 4-OHPPA was reduced by at least one fibre. Inhibition of PA was highest for rutin (8-fold, p < 0.01), then pectin (5-fold, p < 0.01), and ispaghula (2-fold, p = 0.03). Neither rutin nor quercetin had a detectable impact on SCFA production. These interactions should be considered when assessing dietary polyphenols and potential health benefits.

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Section: Discussionmentioning

confidence: 99%

Impact of Fermentable Fibres on the Colonic Microbiota Metabolism of Dietary Polyphenols Rutin and Quercetin

Mansoorian

Combet

Alkhaldy

et al. 2019

IJERPH

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“…PN has been examined independently in the past by other researchers as a potential anti-tumor agent in the treatment of prostate and thyroid cancer, glioma and hematological malignancies [5][6][7][8][9]. PN has been shown to cross the blood brain barrier [10]. PG on the other hand has been studied as a vehicle for nitrogen excretion in humans [11].…”

Section: Introductionmentioning

confidence: 99%

Phenylacetylglutaminate and Phenylacetate in Combination Upregulate VDUP1, Cause Cell Cycle Blockade and Apoptosis in U87 Glioblastoma Cells

Patil¹,

Burzynski²,

Mrowczynski³

et al. 2012

JCT

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Phenylacetylglutaminate (PG) and Phenylacetate (PN) are metabolites of Phenylbutyrate (PB) and are constituents of antineoplaston AS2-1. These are sodium salts of amino acid derivative and carboxylic acid that inhibit the growth of neoplastic cells without growth inhibitory effect in normal cells. The aim of this study was to identify molecular pathways involved in the anti-proliferative effect of antineoplastons. Using a total human genome microarray we have found that 1) Vitamin D3 upregulated protein (VDUP1) is significantly upregulated in response to PG and PN in the U87 glioblastoma cells; 2) Isobologram analysis shows that PG and PN act in an additive or synergistic manner to effectively suppress proliferation of U87 cells; 3) PG and PN cause cell cycle arrest, changes in expression of several cell cycle genes and suppress expression and activity of the G2/M checkpoint kinase, CHK1. The multiple cellular targets possibly make these compounds effective anti-proliferative agents. We propose that PG and PN in combination target important cellular pathways and upregulate VDUP1 leading to detachment-induced apoptosis in cancer cells.

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“…Phenylacetate is a minor product of phenylalanine metabolism normally present in minimum concentrations in human serum and cerebrospinal fluid. 19 Its long-term administration is well tolerated and effective in reducing plasma glutamine levels. This is attractive for cancer intervention strategies, given the dependence of tumor cells on circulating glutamine.…”

Section: Discussionmentioning

confidence: 99%

Phenylacetate Pharmacokinetics Based on Iterative Two‐Stage Population Analysis

et al. 2001

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Phenylacetic acid in human body fluids: high correlation between plasma and cerebrospinal fluid concentration values.

Cited by 40 publications

References 13 publications

Impact of Fermentable Fibres on the Colonic Microbiota Metabolism of Dietary Polyphenols Rutin and Quercetin

Impact of Fermentable Fibres on the Colonic Microbiota Metabolism of Dietary Polyphenols Rutin and Quercetin

Phenylacetylglutaminate and Phenylacetate in Combination Upregulate VDUP1, Cause Cell Cycle Blockade and Apoptosis in U87 Glioblastoma Cells

Phenylacetate Pharmacokinetics Based on Iterative Two‐Stage Population Analysis

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