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Food and Chemical Toxicology : An... May 2019
Review
Topics: Animals; Ecotoxicology; Endpoint Determination; Environmental Pollutants; Humans; Odorants; Perfume; Phenylacetates; Risk Assessment; Salmonella typhimurium
PubMed: 30605701
DOI: 10.1016/j.fct.2018.12.049 -
Microbiology (Reading, England) Dec 2014Ferroglobus placidus was discovered to oxidize completely the aromatic amino acids tyrosine, phenylalanine and tryptophan when Fe(III) oxide was provided as an electron...
Ferroglobus placidus was discovered to oxidize completely the aromatic amino acids tyrosine, phenylalanine and tryptophan when Fe(III) oxide was provided as an electron acceptor. This property had not been reported previously for a hyperthermophilic archaeon. It appeared that F. placidus follows a pathway for phenylalanine and tryptophan degradation similar to that of mesophilic nitrate-reducing bacteria, Thauera aromatica and Aromatoleum aromaticum EbN1. Phenylacetate, 4-hydroxyphenylacetate and indole-3-acetate were formed during anaerobic degradation of phenylalanine, tyrosine and tryptophan, respectively. Candidate genes for enzymes involved in the anaerobic oxidation of phenylalanine to phenylacetate (phenylalanine transaminase, phenylpyruvate decarboxylase and phenylacetaldehyde : ferredoxin oxidoreductase) were identified in the F. placidus genome. In addition, transcription of candidate genes for the anaerobic phenylacetate degradation, benzoyl-CoA degradation and glutaryl-CoA degradation pathways was significantly upregulated in microarray and quantitative real-time-PCR studies comparing phenylacetate-grown cells with acetate-grown cells. These results suggested that the general strategies for anaerobic degradation of aromatic amino acids are highly conserved amongst bacteria and archaea living in both mesophilic and hyperthermophilic environments. They also provided insights into the diverse metabolism of Archaeoglobaceae species living in hyperthermophilic environments.
Topics: Amino Acids, Aromatic; Anaerobiosis; Archaeoglobales; Biotransformation; Gene Expression Profiling; Indoleacetic Acids; Metabolic Networks and Pathways; Microarray Analysis; Molecular Sequence Data; Oxidation-Reduction; Phenylacetates; Real-Time Polymerase Chain Reaction; Sequence Analysis, DNA
PubMed: 25269449
DOI: 10.1099/mic.0.083261-0 -
Environmental Toxicology Feb 2016Epidemiological evidences indicate close association between inorganic arsenic exposure via drinking water and cardiovascular diseases. While the exact mechanism of this...
Epidemiological evidences indicate close association between inorganic arsenic exposure via drinking water and cardiovascular diseases. While the exact mechanism of this arsenic-mediated increase in cardiovascular risk factors remains enigmatic, epidemiological studies indicate a role for paraoxonase 1 (PON1) in cardiovascular diseases. To investigate the association between inorganic arsenic exposure and cardiovascular diseases, rats were exposed to sodium arsenite (trivalent; 50, 100, and 150 ppm As) and sodium arsenate (pentavalent; 100, 150, and 200 ppm As) in their drinking water for 12 weeks. PON1 activity towards paraoxon (PONase) and phenylacetate (AREase) in plasma, lipoproteins, hepatic, and brain microsomal fractions were determined. Inhibition of PONase and AREase in plasma and HDL characterized the effects of the two arsenicals. While the trivalent arsenite inhibited PONase by 33% (plasma) and 46% (HDL), respectively, the pentavalent arsenate inhibited the enzyme by 41 and 34%, respectively. AREase activity was inhibited by 52 and 48% by arsenite, whereas the inhibition amounted to 72 and 67%, respectively by arsenate. The pattern of inhibition in plasma and HDL indicates that arsenite induced a dose-dependent inhibition of PONase whereas arsenate induced a dose-dependent inhibition of AREase. In the VLDL + LDL, arsenate inhibited PONase and AREase while arsenite inhibited PONase. In the hepatic and brain microsomal fractions, only the PONase enzyme was inhibited by the two arsenicals. The inhibition was more pronounced in the hepatic microsomes where a 70% inhibition was observed at the highest dose of pentavalent arsenic. Microsomal cholesterol was increased by the two arsenicals resulting in increased cholesterol/phospholipid ratios. Our findings indicate that decreased PON1 activity observed in arsenic exposure may be an incipient biochemical event in the cardiovascular effects of arsenic. Modulation of PON1 activity by arsenic may also be mediated through changes in membrane fluidity brought about by changes in the concentration of cholesterol in the microsomes.
Topics: Animals; Arsenicals; Aryldialkylphosphatase; Brain Chemistry; Cholesterol, HDL; Cholesterol, LDL; Cholesterol, VLDL; Dose-Response Relationship, Drug; Drinking Water; Insecticides; Male; Microsomes; Microsomes, Liver; Paraoxon; Phenylacetates; Rats; Rats, Wistar; Water Pollutants, Chemical
PubMed: 25082665
DOI: 10.1002/tox.22030 -
Plant Physiology Jun 2019Polar auxin transport plays a pivotal role in plant growth and development. PIN-FORMED (PIN) auxin efflux carriers regulate directional auxin movement by establishing...
Polar auxin transport plays a pivotal role in plant growth and development. PIN-FORMED (PIN) auxin efflux carriers regulate directional auxin movement by establishing local auxin maxima, minima, and gradients that drive multiple developmental processes and responses to environmental signals. Auxin has been proposed to modulate its own transport by regulating subcellular PIN trafficking via processes such as clathrin-mediated PIN endocytosis and constitutive recycling. Here, we further investigated the mechanisms by which auxin affects PIN trafficking by screening auxin analogs and identified pinstatic acid (PISA) as a positive modulator of polar auxin transport in Arabidopsis (). PISA had an auxin-like effect on hypocotyl elongation and adventitious root formation via positive regulation of auxin transport. PISA did not activate SCF signaling and yet induced PIN accumulation at the cell surface by inhibiting PIN internalization from the plasma membrane. This work demonstrates PISA to be a promising chemical tool to dissect the regulatory mechanisms behind subcellular PIN trafficking and auxin transport.
Topics: Arabidopsis; Arabidopsis Proteins; Biological Transport; Cell Membrane; Endocytosis; Gravitropism; Hypocotyl; Indoleacetic Acids; Phenotype; Phenylacetates; Plant Roots; Plant Shoots; Signal Transduction
PubMed: 30936248
DOI: 10.1104/pp.19.00201 -
Archives of Pharmacal Research Sep 2019The aim of this work was to evaluate the synthesis and structure-activity relationship of 4-((2,4-dioxothiazolidin-5-ylidene)methyl)phenyl 2-phenylacetate derivatives as...
The aim of this work was to evaluate the synthesis and structure-activity relationship of 4-((2,4-dioxothiazolidin-5-ylidene)methyl)phenyl 2-phenylacetate derivatives as potential wound-healing agents. The IC values of the lead compounds ranged from 0.01 to 0.05 µM. These compounds also increased the levels of extracellular prostaglandin E (PGE) in A549 cells. Among the synthesized compounds, compounds 66, 67, 69, and 86 increased PGE levels 3- to 4-fold of those achieved with the negative control. Introduction of a halogen at the intermediate phenyl ring, compounds 66, 67, 69, and 86 resulted in higher IC values, which indicated lower cytotoxicity than that observed upon the introduction of other substituents at the same position. In particular, cells exposed to compound 69 showed significantly improved wound healing, and the wound closure rate achieved was approximately 3.2-fold higher than that of the control. Therefore, compound 69 can be used for tissue regeneration and treatment of diverse diseases caused by PGE deficiency. Overall, our findings suggested that compound 69 might be a novel candidate for skin wound therapy.
Topics: A549 Cells; Dinoprostone; Dose-Response Relationship, Drug; Humans; Molecular Structure; Phenylacetates; Structure-Activity Relationship; Thiazolidinediones; Wound Healing
PubMed: 29948772
DOI: 10.1007/s12272-018-1041-3 -
Journal of Affective Disorders Mar 2024Biochemical changes of neurotransmitters underlying major depressive disorder (MDD) are unknown. This study preliminarily explored the association between...
BACKGROUND & AIMS
Biochemical changes of neurotransmitters underlying major depressive disorder (MDD) are unknown. This study preliminarily explored the association between neurotransmitters with MDD and the possibility of objective laboratory prediction of neurotransmitter involvement in MDD.
METHODS
A total of 87 first-diagnosed, drug-naïve patients with depression and 50 healthy controls (HCs) were included in the cross-sectional study. The levels and turnovers of neurotransmitters (glutamine (GLN), glutamic acid (GLU), γ-2Aminobutiric acid (GABA), kainate (KA), vanillylmandelic acid (VMA), 3-methoxy 4-hydroxyphenyl ethylene glycol (MHPG), noradrenaline (NE), homovanillic acid (HVA), dihydroxy-phenyl acetic acid (DOPAC), dopamine (DA), tryptophane (TRP), kynurenine (KYN), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA)) were determined and the confounding factors were adjusted. Then a correlation and a predictive analysis towards neurotransmitters for MDD were performed.
RESULTS
After adjusting confounding factors, GLU (OR = 1.159), (GLU+ GABA)/GLN (OR = 1.217), DOPAC (OR = 1.106), DOPAC/DA (OR = 1.089) and (DOPAC+ HVA)/DA (OR = 1.026) enacted as risk factors of MDD, while KYN (OR = 0.992) was a protective factor. GABAergic and TRPergic pathways were associated with severity of depressive and anxiety symptoms in patients with depression. The predictive model for MDD (AUC = 0.775, 95%CI 0.683-0.860) consisted of KYN (OR = 0.990) and (GLU + GABA)/GLN (OR = 4.101).
CONCLUSIONS
First-diagnosed, drug-naïve depression patients showed abnormal neurotransmitter composition. GLU, (GLU + GABA)/GLN, DOPAC, DOPAC/DA and (DOPAC + HVA)/DA were risk factors of MDD, while KYN was a protective factor. GABAergic and TRPergic pathways were correlated with MDD clinical characteristics. KYN and (GLU + GABA)/GLN may have a predictive value for MDD.
Topics: Humans; Depressive Disorder, Major; Depression; 3,4-Dihydroxyphenylacetic Acid; Cross-Sectional Studies; Dopamine; Neurotransmitter Agents; Homovanillic Acid; Kynurenine; Glutamic Acid; Glutamine; Serotonin; gamma-Aminobutyric Acid; Phenylacetates
PubMed: 38199403
DOI: 10.1016/j.jad.2024.01.023 -
Journal of the American Chemical Society Oct 2022With the large number of Pd(II)-catalyzed C-H activation reactions of native substrates developed in the past decade, the development of catalysts to enable the use of...
With the large number of Pd(II)-catalyzed C-H activation reactions of native substrates developed in the past decade, the development of catalysts to enable the use of green oxidants under safe and practical conditions has become an increasingly important challenge. Notably, the compatibility of Pd(II) catalysts with sustainable aqueous HO has been a long-standing challenge in catalysis including Wacker-type oxidations. We report herein a bifunctional bidentate carboxyl-pyridone (CarboxPyridone) ligand that enables room-temperature Pd-catalyzed C-H hydroxylation of a broad range of benzoic and phenylacetic acids with an industry-compatible oxidant, aqueous hydrogen peroxide (35% HO). The scalability of this methodology is demonstrated by a 1000 mmol scale reaction of ibuprofen (206 g) using only a 1 mol % Pd catalyst loading. The utility of this protocol is further illustrated through derivatization of the products and synthesis of polyfluorinated natural product coumestan and pterocarpene from phenol intermediates prepared using this methodology.
Topics: Biological Products; Catalysis; Hydrogen Peroxide; Hydroxylation; Ibuprofen; Ligands; Oxidants; Palladium; Phenols; Phenylacetates; Pyridones; Temperature; Water
PubMed: 36137252
DOI: 10.1021/jacs.2c08332 -
Journal of Chromatography. B,... Apr 2015We present a method for the qualitative and quantitative analysis of felbinac and its major metabolites in human plasma and urine by HPLC-MS/MS and its application....
Qualitative and quantitative analysis of felbinac and its major metabolites in human plasma and urine by liquid chromatography tandem mass spectrometry and its application after intravenous administration of felbinac trometamol injection.
We present a method for the qualitative and quantitative analysis of felbinac and its major metabolites in human plasma and urine by HPLC-MS/MS and its application. Qualitative analysis through LC-Triple-TOF-MS/MS indicated that oxidization was the main phase-I metabolic pathway of felbinac in human, conjugation with sulfate and glucuronide groups produced at least 7 phase-II metabolites. Quantitative analysis through HPLC-MS/MS in MRM mode was developed and validated for the quantification of felbinac and its major metabolite (4'-hydroxyfelbinac) in human plasma and urine. Linear calibration curves were obtained for felbinac and 4'-hydroxyfelbinac in plasma and urine (r>0.996); intra- and inter-day precision values (RSD%) obtained were ranged from 1.13 to 6.49%, and the accuracy were between 95.9% and 108.6% for the two analytes. The pharmacokinetics and excretion analysis showed that the t1/2 of 4'-hydroxyfelbinac (8.25 ± 4.15 h) is a litter longer than that of felbinac (6.13 ± 2.01 h), but the mean AUC(0-t) value of felbinac was about 20 times higher than that of 4'-hydroxyfelbinac; excretion of felbinac and 4'-hydroxyfelbinac reached their peak values at about 3-6h after intravenous administration of felbinac trometamol in human.
Topics: Administration, Intravenous; Adult; Chromatography, High Pressure Liquid; Drug Stability; Humans; Linear Models; Male; Phenylacetates; Reproducibility of Results; Sensitivity and Specificity; Tandem Mass Spectrometry; Young Adult
PubMed: 25706568
DOI: 10.1016/j.jchromb.2015.01.042 -
BMC Veterinary Research Aug 2018Robenacoxib is a non-steroidal anti-inflammatory drug available for canine and feline use for the control of pain and inflammation marketed as Onsior™. The aim of this... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Robenacoxib is a non-steroidal anti-inflammatory drug available for canine and feline use for the control of pain and inflammation marketed as Onsior™. The aim of this target animal safety study was to evaluate the 6-month safety profile of oral robenacoxib administration. It was a randomized, negative-controlled, parallel group study. Thirty-two healthy, young, experimentally naïve, purebred Beagle dogs were administered 0 (sham control, Group 1), 2, 6, and 10 mg/kg robenacoxib (corresponding to the upper end of the dosage range [1X, Group 2] and multiples thereof [3X and 5X, Group 3 and 4]), orally once daily for 6 months. Assessment of safety included general health and clinical observations, physical, neurological, ophthalmological and electrocardiographic examinations, gross and histopathological examinations and clinical pathology evaluations. Blood samples were collected for toxicokinetic assessment of robenacoxib.
RESULTS
No serious adverse events were reported. When compared with control, no treatment effect was observed for body weight, feed or water consumption, clinical pathology, urinalysis and fecal examination parameters. There were no treatment-related changes in stifle joint tissues and microscopic/histopathology examinations of all tissues/organs were normal. Salivation and soft feces were noted in all groups but observed more frequently in the treated groups as compared with control. On Day 178, increased buccal mucosal bleeding times were observed in two treated animals (Group 3 and 4) and one dog in Group 4 displayed a retinal change. Decreased hopping and conscious proprioception was noted in four treated dogs. One dog in Group 2 had ventricular premature complexes. Post-mortem changes included mild, red foci on the cecum in one dog (Group 3) and minimal duodenal discoloration in one dog (Group 4), with no corresponding histological findings in either dog. Ovarian weights were decreased in females from Group 3 and 4 with no gross or histological changes in the ovaries. Blood concentrations of robenacoxib confirmed systemic exposure of treated dogs. Exposure increased with increasing doses and there were no accumulation of robenacoxib in blood.
CONCLUSIONS
Robenacoxib was well tolerated at doses from 2 to 10 mg/kg/day and this 6-month study supports the safe use of Onsior™ (robenacoxib) tablets in dogs for the intended dosing regimen.
Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Diphenylamine; Dogs; Dose-Response Relationship, Drug; Female; Male; Organ Size; Ovary; Phenylacetates; Tablets
PubMed: 30119677
DOI: 10.1186/s12917-018-1566-1 -
Journal of the American Academy of... Jan 2023The combination of d-methylphenidate and guanfacine (an α-2A adrenergic agonist) may be an effective alternative to either agent as monotherapy in children with... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
The combination of d-methylphenidate and guanfacine (an α-2A adrenergic agonist) may be an effective alternative to either agent as monotherapy in children with attention-deficit/hyperactivity disorder (ADHD). This study investigated the neural mechanisms underlying medication effects using cortical source analysis of electroencephalography (EEG) data.
METHOD
A total of 172 children with ADHD (aged 7-14; 118 boys) completed an 8-week randomized, double-blind, comparative study with 3 treatment arms: d-methylphenidate, guanfacine, or their combination. EEG modulations of brain oscillations at baseline and end point were measured during a spatial working memory task from cortical sources localized within the anterior cingulate (midfrontal) and primary visual cortex (midoccipital), based on previously reported ADHD and control differences. Linear mixed models examined treatment effects on EEG and performance measures.
RESULTS
Combined treatment decreased midoccipital EEG power across most frequency bands and task phases. Several midoccipital EEG measures also showed significantly greater changes with combined treatment than with monotherapies. D-methylphenidate significantly increased midoccipital theta during retrieval, while guanfacine produced only trend-level reductions in midoccipital alpha during maintenance and retrieval. Task accuracy improved with combined treatment, was unchanged with d-methylphenidate, and worsened with guanfacine. Treatment-related changes in midoccipital power correlated with improvement in ADHD severity.
CONCLUSION
These findings show that combined treatment ameliorates midoccipital neural activity associated with treatment-related behavioral improvements and previously implicated in visuo-attentional deficits in ADHD. Both monotherapies had limited effects on EEG measures, with guanfacine further showing detrimental effects on performance. The identified midoccipital EEG profile may aid future treatment monitoring for children with ADHD.
CLINICAL TRIAL REGISTRATION INFORMATION
Single Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder (Project1); https://clinicaltrials.gov/; NCT00429273.
DIVERSITY & INCLUSION STATEMENT
We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure sex and gender balance in the recruitment of human participants. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. We actively worked to promote sex and gender balance in our author group.
Topics: Male; Child; Female; Humans; Attention Deficit Disorder with Hyperactivity; Guanfacine; Methylphenidate; Memory, Short-Term; Electroencephalography; Central Nervous System Stimulants
PubMed: 35963558
DOI: 10.1016/j.jaac.2022.06.017