Pregnenolone 16α-carbonitrile negatively regulates hippocampal cytochrome P450 enzymes and ameliorates phenytoin-induced hippocampal neurotoxicity DOI Creative Commons
Shuai Zhang, Tingting Wang,

YE Feng

et al.

Journal of Pharmaceutical Analysis, Journal Year: 2023, Volume and Issue: 13(12), P. 1510 - 1525

Published: July 25, 2023

The central nervous system is susceptible to the modulation of various neurophysiological processes by cytochrome P450 enzyme (CYP), which plays a crucial role in metabolism neurosteroids. antiepileptic drug phenytoin (PHT) has been observed induce neuronal side effects patients, could be attributed its induction CYP expression and testosterone (TES) hippocampus. While pregnane X receptor (PXR) widely known for regulatory function CYPs liver, we have discovered that treatment mice with pregnenolone 16α-carbonitrile (PCN), PXR agonist, differential on liver Specifically, PCN resulted P450, family 3, subfamily a, polypeptide 11 (CYP3A11), CYP2B10 while suppressing their Functionally, protected from PHT-induced hippocampal nerve injury, was accompanied inhibition TES Mechanistically, found attenuation neurotoxicity were glucocorticoid dependent, rather than independent, as demonstrated genetic pharmacological models. In conclusion, our study provides evidence can negatively regulate attenuate independently PXR. Our findings suggest glucocorticoids may potential therapeutic strategy managing PHT.

Language: Английский

Fabrication of a surface molecularly imprinted polymer membrane based on a single template and its application in the separation and extraction of phenytoin, phenobarbital and lamotrigine DOI Creative Commons
Yanlin Zhao,

Yu-xin You,

Yu‐lang Chen

et al.

RSC Advances, Journal Year: 2024, Volume and Issue: 14(12), P. 8353 - 8365

Published: Jan. 1, 2024

A molecularly imprinted polymer membrane (MIPM) was prepared using PVDF as the support and phenytoin (PHT) a single template. The results indicated that MIPMs can be used to extract PHT, phenobarbital, lamotrigine in different matrices.

Language: Английский

Citations

4
Temperature- and chemical-induced neurotoxicity in zebrafish DOI Creative Commons
Mattia Toni, Chiara Arena,

Carla Cioni

et al.

Frontiers in Physiology, Journal Year: 2023, Volume and Issue: 14

Published: Oct. 3, 2023

Throughout their lives, humans encounter a plethora of substances capable inducing neurotoxic effects, including drugs, heavy metals and pesticides. Neurotoxicity manifests when exposure to these chemicals disrupts the normal functioning nervous system, some agents have been linked neurodegenerative pathologies such as Parkinson's Alzheimer's disease. The growing concern surrounding impacts both naturally occurring man-made toxic necessitates identification animal models for rapid testing across wide spectrum concentrations, utilization tools detecting system alterations spanning from molecular level up behavioural one. Zebrafish (Danio rerio) is gaining prominence in field neuroscience due its versatility. possibility analysing all developmental stages (embryo, larva adult), applying most common "omics" approaches (transcriptomics, proteomics, lipidomics, etc.) conducting range tests makes zebrafish an excellent model neurotoxicity studies. This review delves into main experimental adopted markers analysed studies zebrafish, showing that phenomena can be triggered not only by chemical but also fluctuations temperature. findings presented here serve valuable resource study define new scenarios ecotoxicology suggesting temperature synergistically compound effects substances, intensifying detrimental impact on fish populations.

Language: Английский

Citations

10
Determination of phenytoin at trace levels in domestic wastewater and synthetic urine samples by gas chromatography-mass spectrometry after its preconcentration by simple liquid-phase microextraction DOI
Sezin Erarpat,

Gizem Nur Ayan,

Süleyman Bodur

et al.

Environmental Monitoring and Assessment, Journal Year: 2024, Volume and Issue: 196(5)

Published: April 15, 2024

Language: Английский

Citations

2
Developmental toxicity of the emerging contaminant cyclophosphamide and the integrated biomarker response (IBRv2) in zebrafish DOI
Tamilselvan Hema, Rama-Krishnan Poopal, Mathan Ramesh

et al.

Environmental Science Processes & Impacts, Journal Year: 2023, Volume and Issue: 25(8), P. 1391 - 1406

Published: Jan. 1, 2023

The safety of cyclophosphamide (CP) in the early developmental stages is not studied yet; it important to study responses at these because they might have relevance CP-administered humans. We toxicity CP by analysing physiological, morphological, and oxidative stress, neurotransmission enzymes, gene expression histological endpoints zebrafish embryos/larvae. lasted for 120 hpf environmentally relevant concentrations CP. No visible alterations were noticed control group. Delayed hatching, slow heart rate, yolk sac oedema, pericardial morphological deformities, incompetence stress biomarkers, excessive generation ROS, apoptosis, inhibition neurotransmitters histopathological anomalies observed CP-treated groups. These found be concentration- duration-dependent effects physiological endpoints, whereas concentration-dependent antioxidants, apoptosis endpoints. Biomarkers standardised using integrated biomarker response-IBRv2 index. IBRv2 index showed a behaviour. A non-lethal teratogenic effect was embryos/larvae concentrations. biomarkers are sensitive, interrelated; thus, their useful assess veiled unseen hazards pharmaceuticals.

Language: Английский

Citations

5
Phenytoin causes behavioral abnormalities and suppresses kisspeptin expression, reducing reproductive performance in Japanese medaka DOI

Kensuke Mitsunaga,

Sheikh Shohag,

C. Ming

et al.

Aquatic Toxicology, Journal Year: 2024, Volume and Issue: 273, P. 107007 - 107007

Published: June 21, 2024

Language: Английский

Citations

1
Behavioral profile alterations and predation susceptibility of Japanese medaka fish exposed to phenytoin, an antiepileptic drug DOI

Ayaka Sawada,

Dorcas Uaciquete, Yoshifumi Horie

et al.

Environmental Toxicology and Pharmacology, Journal Year: 2024, Volume and Issue: 108, P. 104474 - 104474

Published: May 17, 2024

Language: Английский

Citations

1
Pregnenolone 16α-carbonitrile negatively regulates hippocampal cytochrome P450 enzymes and ameliorates phenytoin-induced hippocampal neurotoxicity DOI Creative Commons
Shuai Zhang, Tingting Wang,

YE Feng

et al.

Journal of Pharmaceutical Analysis, Journal Year: 2023, Volume and Issue: 13(12), P. 1510 - 1525

Published: July 25, 2023

The central nervous system is susceptible to the modulation of various neurophysiological processes by cytochrome P450 enzyme (CYP), which plays a crucial role in metabolism neurosteroids. antiepileptic drug phenytoin (PHT) has been observed induce neuronal side effects patients, could be attributed its induction CYP expression and testosterone (TES) hippocampus. While pregnane X receptor (PXR) widely known for regulatory function CYPs liver, we have discovered that treatment mice with pregnenolone 16α-carbonitrile (PCN), PXR agonist, differential on liver Specifically, PCN resulted P450, family 3, subfamily a, polypeptide 11 (CYP3A11), CYP2B10 while suppressing their Functionally, protected from PHT-induced hippocampal nerve injury, was accompanied inhibition TES Mechanistically, found attenuation neurotoxicity were glucocorticoid dependent, rather than independent, as demonstrated genetic pharmacological models. In conclusion, our study provides evidence can negatively regulate attenuate independently PXR. Our findings suggest glucocorticoids may potential therapeutic strategy managing PHT.

Language: Английский

Citations

0