A5052147035- Computational Drug Discovery Methods
- Pharmacological Effects and Assays
- Pharmacogenetics and Drug Metabolism
- Per- and polyfluoroalkyl substances research
- Drug Transport and Resistance Mechanisms
- Effects and risks of endocrine disrupting chemicals
- Carcinogens and Genotoxicity Assessment
- 3D Printing in Biomedical Research
- Liver physiology and pathology
- Pharmacology and Obesity Treatment
- Air Quality and Health Impacts
- Veterinary Pharmacology and Anesthesia
- Toxic Organic Pollutants Impact
- Pluripotent Stem Cells Research
- Receptor Mechanisms and Signaling
Wageningen University & Research
2020-2024
Maastricht University
2024
The goal of the present study was to develop an online web-based toolbox that contains generic physiologically based kinetic (PBK) models for rats and humans, including underlying calculation tools predict plasma protein binding tissue:plasma distribution, be used quantitative in-vitro-to-in-vivo extrapolations (QIVIVE). PBK within allow first estimations internal tissue concentrations chemicals made, on logP pKa values intestinal uptake intrinsic hepatic clearance. As a case study, oral...
The goal of the present study was to assess predictive performance a generic human physiologically based kinetic (PBK) model on in vitro and silico input data effect using different approaches for chemical parameterization those predictions. For this purpose, dataset created 38,772 Cmax predictions 44 compounds by applying combinations parameterization, these predicted values were compared reported vivo data. Best results achieved when hepatic clearance parameterized (i.e., hepatocytes or...
The goal of the present study was to assess predictive performance a minimal generic rat physiologically based kinetic (PBK) model on in vitro and silico input data predict peak plasma concentrations (Cmax) upon single oral dosing. To this purpose, dataset generated 3960 Cmax predictions for 44 compounds, applying different combinations approaches chemical parameterization, comparison reported vivo data. Best obtained when (1) hepatic clearance parameterized measured intrinsic values, (2)...
Abstract Humans can be exposed to per- and polyfluoroalkyl substances (PFASs) via many exposure routes, including diet, which may lead several adverse health effects. So far, little is known about PFAS transport across the human intestinal barrier. In current study, we aimed assess of 5 PFASs (PFOS, PFOA, PFNA, PFHxS HFPO-DA) in a induced pluripotent stem cell (hiPSC)-derived epithelial (IEC) model. This model was extensively characterized compared with widely applied colonic adenocarcinoma...
Abstract Flow conditions have been shown to be important in improving longevity and functionality of primary hepatocytes, but the impact flow on HepaRG cells is largely unknown. We studied expression genes encoding CYP enzymes transporter proteins CYP1 CYP3A4 activity during 8 weeks culture cultured under static (conventional 24-/96-well plate with common bicarbonate/CO 2 buffering) an organ-on-chip (OOC) device. Since OOC-device a closed system, buffering was not possible, requiring...
Abstract Per- and polyfluoroalkyl substances (PFASs) are omnipresent have been shown to induce a wide range of adverse effects, including hepatotoxicity, developmental toxicity immunotoxicity. So far, little information is available about the mechanisms underlying PFASs, those related their Reported immunotoxic effects PFASs include decreased antibody responses in experimental animals humans, indicating that may, among others, affect B cell function. In present study, we first assessed PFOA...
Pre-workout supplements are popular among sport athletes and overweight individuals. Phenethylamines (PEAs) alkylamines (AA) widely present in these supplements. Although the health effects of analogues not well understood yet, they hypothesised to be agonists adrenergic (ADR) trace amine-associated receptors (TAARs). Therefore, we aimed pharmacologically characterise compounds by investigating their activating properties ADRs TAAR1 vitro. The potency efficacy selected PEAs AAs was studied...
In vitro models are widely used to study the biotransformation of xenobiotics and provide input parameters physiologically based kinetic required predict behavior in vivo. For farm animals this is not common practice yet. The use slaughterhouse-derived tissue material may opportunities reactions animals. goal present was explore potential bovine liver S9 (S9) precision cut slices (PCLSs) capture observed lidocaine cows. data obtained with both PCLSs confirm vivo findings that...