A5001597354- Drug Transport and Resistance Mechanisms
- Pharmacogenetics and Drug Metabolism
- Reproductive Biology and Fertility
- Pharmacological Effects and Toxicity Studies
- Diet and metabolism studies
- Organ Transplantation Techniques and Outcomes
- Metal complexes synthesis and properties
- 3D Printing in Biomedical Research
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Drug-Induced Hepatotoxicity and Protection
- Helicobacter pylori-related gastroenterology studies
- Sperm and Testicular Function
- Digestive system and related health
- Liver physiology and pathology
- Clinical Nutrition and Gastroenterology
- Smoking Behavior and Cessation
- Polyamine Metabolism and Applications
- Heat shock proteins research
- Cancer Cells and Metastasis
- Dendrimers and Hyperbranched Polymers
- N-Heterocyclic Carbenes in Organic and Inorganic Chemistry
- Pregnancy and Medication Impact
- Tissue Engineering and Regenerative Medicine
- Epigenetics and DNA Methylation
University Medical Center Groningen
2022-2024
University of Groningen
2013-2022
Target (United States)
2007-2017
Engie (United States)
2017
Abbott (Germany)
2013
Solvay (Netherlands)
2000-2006
Solvay (Belgium)
2002
Food & Nutrition
2000
The transcription factor nuclear erythroid 2-related 2 (Nrf2) is considered as the master regulator of antioxidant and cytoprotective gene expressions. Moreover, it plays a pivotal role in cancer progression. Nrf2 mediates adaptive response which contributes to resistance chemotherapeutic pro-oxidant drugs, such cisplatin (CDDP), various tumors, including bladder cancers. For this reason, could be promising target overcome chemoresistance. There are several known pharmacological inhibitors;...
We report on an improved method of synthesis N-benzylaminoferrocene-based prodrugs and demonstrate its applicability by preparing nine new aminoferrocenes. Their effect the viability selected cancer cells having different p53 status was studied. The obtained data are in agreement with hypothesis that toxicity aminoferrocenes is not dependent upon status. Subsequently a prodrug (4) investigated ex vivo using rat precision cut liver slices hybrid male mice BDF1. In both experiments no...
Five platinum(II) complexes bearing a (1,3-dibenzyl)imidazol-2-ylidene ligand but different leaving groups trans to it were examined for cytotoxicity, DNA and cell cycle interference, vascular disrupting properties, nephrotoxicity. The cytotoxicity of 3a-c increased with the steric shielding their chloride ligand, complex 3c, featuring two triphenylphosphanes, was most efficacious, submicromolar IC50 concentrations. Complexes interacted in electrophoretic mobility shift ethidium bromide...
Predictive in vitro methods to investigate drug metabolism the human intestine using intact tissue are of high importance. Therefore, we studied metabolic activity small intestinal and colon slices compared it with same segments Ussing chamber technique. The was evaluated substrates both phase I II reactions: testosterone, 7-hydroxycoumarin (7HC), a mixture cytochrome P450 (P450) (midazolam, diclofenac, coumarin, bufuralol). In proximal jejunum, several P450-mediated conjugation reactions...
Induction of drug enzyme activity in the intestine can strongly determine plasma levels drugs. It is therefore important to predict drug-drug interactions human vitro. We evaluated applicability intestinal precision-cut slices for induction studies Morphological examination and intracellular ATP indicated tissue integrity up 24 h incubation, whereas proximal jejunum slices, metabolic rate toward most substrates remained at 40 50% initial values. In colon cytochrome P450 conversions were...
A series of organometallic AuI N-heterocyclic carbene (NHC) complexes was synthesized and characterized for anticancer activity in four human cancer cell lines. The compounds' toxicity healthy tissue determined using precision-cut kidney slices (PCKS) as a tool to determine the potential selectivity gold ex vivo. All evaluated compounds presented cytotoxic toward cells nano- or low micromolar range. mixed NHC complex, (tert-butylethynyl)-1,3-bis-(2,6-diisopropylphenyl)imidazol-2-ylidene...
The aim of this study was to characterize rat small intestinal and colon tissue slices as a tool metabolism investigate gradients drug along the tract well drug-induced inhibition induction biotransformation. Tissue morphology mucus layer remained intact in during 3 h incubation, while alkaline phosphatase retained rate three model compounds (7-hydroxycoumarin, 7-ethoxycoumarin, testosterone) appeared constant. Phase I phase II metabolic gradients, decreasing from stomach toward were shown...
Abstract1. The aim was to investigate whether precision-cut rat tissue slices could be used predict metabolic drug clearance in vivo. To obtain a complete picture, not only from liver, but also lung, kidney, small intestine and colon were included.2. clearances of 7-ethoxycoumarin, 7-hydroxycoumarin, testosterone, methyltestosterone warfarin determined by measuring the disappearance these compounds during incubation with prepared colon.3. total vitro adding individual organ slices....
A novel approach for on-line monitoring of drug metabolism in continuously perifused, precision-cut liver slices (PCLS) a microfluidic system has been developed using high-performance liquid chromatography with UV detection (HPLC-UV). In this approach, PCLS are incubated device made poly(dimethylsiloxane) (PDMS) by continuous, single-pass perifusion fresh medium. Two syringe pumps incorporated into the to infuse substrates or inhibitors at varying concentrations perfusion medium just before...
Various in vitro preparations were compared with respect to their ability mimic vivo metabolism. For this purpose, S9-liver homogenate, microsomes, cryopreserved hepatocytes, liver slices and fresh liver, lung, kidney, intestinal incubated three drugs development, which are metabolized by a wide range of biotransformation pathways. Metabolites identified quantified liquid chromatography-mass spectometry/UV from the incubations metabolite patterns feces, urine, bile dosed rats. In systems...
Tissue slices have been shown to be a valuable tool predict metabolism of novel drugs. However, besides the numerous advantages their use for this purpose, some potential drawbacks also exist, including reported poor penetration drugs into inner cell layers and loss metabolic capacity during prolonged incubation, leading underprediction clearance. In present study, we empirically identified (and quantified) sources using rat tissue lung, intestine, kidney, liver found that thin (+/-100 mum)...
The aim of this study was to evaluate drug metabolism in rat small intestinal and colon precision-cut slices during 24 h incubation the applicability these for enzyme induction studies. Various parameters were evaluated: intracellular levels ATP (general viability marker), alkaline phosphatase activity (specific epithelial villin expression metabolic rates 7-ethoxycoumarin (CYP1A), testosterone (CYP3A CYP2B), 7-hydroxycoumarin (glucuronide sulfate conjugation) conversions. remained constant...
Intestinal fibrosis (IF) is a major complication of inflammatory bowel disease. IF research limited by the lack relevant in vitro and vivo models. We evaluated precision-cut intestinal slices (PCIS) prepared from human, rat, mouse intestine as ex models mimicking early-onset (human) IF. Precision-cut human (h), rat (r), (m) jejunum, were incubated up to 72 h, viability PCIS was assessed ATP content morphology, gene expression several markers determined. The rPCIS decreased after 24 h...
A study of occupational exposure to paraquat was performed among 11 knapsack spray operators at banana plantations in Costa Rica. External and internal exposures were quantified determinants identified by measurements, observations, interviews. Dermal measured with skin pads, respiratory personal air sampling, urine sampling. The wrists, back, legs the areas highest levels dermal exposure. Respiratory appeared be strongly influenced differences between days, while varied mostly due...
The role of the intestine in drug metabolism has long been underestimated as a consequence technical difficulty to discern from that liver vivo experiments and lack vitro models are sufficiently viable fully representing physiology anatomy intestine. Recently precision-cut slice model, which is widely used for kidney, was also adapted small large In this review application intestinal slices (PCIS) research transport discussed. PCIS can be prepared animal human tissues all regions allowing...
The toxic effects and accumulation mechanisms of cisplatin in healthy rat kidneys has been studied<italic>ex vivo</italic>, using the Precision Cut Tissue Slices (PCTS) method, comparison to those exerted by an experimental cytotoxic Au(<sc>iii</sc>) compound.