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Open AccessBasic concepts of mixture toxicity and relevance for risk evaluation and regulation
Exposure to multiple substances is a challenge for risk evaluation. Currently, there is an ongoing debate if generic “mixture assessment/allocation factors” (MAF) should be introduced to increase public health...
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Open AccessInhibition of cytochrome P450 enhances the nephro- and hepatotoxicity of ochratoxin A
The mycotoxin ochratoxin A (OTA) is a contaminant in food that causes nephrotoxicity and to a minor degree hepatotoxicity. Recently, we observed that OTA induces liver damage preferentially to the cytochrome P...
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Open AccessColchicine overdose impairs the capacity of Kupffer cells to clear foreign particles and endotoxins
Colchicine is an anti-inflammatory drug with a narrow therapeutic index. Its binding to tubulin prevents microtubule polymerization; however, little is known about how depolymerization of microtubules interfer...
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Open AccessHypoalbuminemia affects the spatio-temporal tissue distribution of ochratoxin A in liver and kidneys: consequences for organ toxicity
Hypoalbuminemia (HA) is frequently observed in systemic inflammatory diseases and in liver disease. However, the influence of HA on the pharmacokinetics and toxicity of compounds with high plasma albumin bindi...
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Correction to: Toxicogenomics directory of chemically exposed human hepatocytes
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Open AccessContribution to the ongoing discussion on fluoride toxicity
Since the addition of fluoride to drinking water in the 1940s, there have been frequent and sometimes heated discussions regarding its benefits and risks. In a recently published review, we addressed the quest...
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Open AccessToxicity of fluoride: critical evaluation of evidence for human developmental neurotoxicity in epidemiological studies, animal experiments and in vitro analyses
Recently, epidemiological studies have suggested that fluoride is a human developmental neurotoxicant that reduces measures of intelligence in children, placing it into the same category as toxic metals (lead,...
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Inflammation-associated suppression of metabolic gene networks in acute and chronic liver disease
Inflammation has been recognized as essential for restorative regeneration. Here, we analyzed the sequential processes during onset of liver injury and subsequent regeneration based on time-resolved transcript...
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Open AccessPrediction of human drug-induced liver injury (DILI) in relation to oral doses and blood concentrations
Drug-induced liver injury (DILI) cannot be accurately predicted by animal models. In addition, currently available in vitro methods do not allow for the estimation of hepatotoxic doses or the determination of ...
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Relevance of the incubation period in cytotoxicity testing with primary human hepatocytes
Primary human hepatocytes (PHHs) remain the gold standard for in vitro testing in the field of pharmacology and toxicology. One crucial parameter influencing the results of in vitro tests is the incubation per...
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Toxicogenomics directory of rat hepatotoxicants in vivo and in cultivated hepatocytes
Transcriptomics is develo** into an invaluable tool in toxicology. The aim of this study was, using a transcriptomics approach, to identify genes that respond similar to many different chemicals (including d...
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Adverse outcome pathways: opportunities, limitations and open questions
Adverse outcome pathways (AOPs) are a recent toxicological construct that connects, in a formalized, transparent and quality-controlled way, mechanistic information to apical endpoints for regulatory purposes....
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GDPD5, a choline-generating enzyme and its novel role in tumor cell migration
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Open AccessGene network activity in cultivated primary hepatocytes is highly similar to diseased mammalian liver tissue
It is well known that isolation and cultivation of primary hepatocytes cause major gene expression alterations. In the present genome-wide, time-resolved study of cultivated human and mouse hepatocytes, we mad...
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Highlight report: redox—metals in toxicology
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Open AccessA transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors
Test systems to identify developmental toxicants are urgently needed. A combination of human stem cell technology and transcriptome analysis was to provide a proof of concept that toxicants with a related mod...
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Toxicogenomics directory of chemically exposed human hepatocytes
A long-term goal of numerous research projects is to identify biomarkers for in vitro systems predicting toxicity in vivo. Often, transcriptomics data are used to identify candidates for further evaluation. H...
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Progress in ‘body-on-a-chip’ research
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Open AccessProtocols for staining of bile canalicular and sinusoidal networks of human, mouse and pig livers, three-dimensional reconstruction and quantification of tissue microarchitecture by image processing and analysis
Histological alterations often constitute a fingerprint of toxicity and diseases. The extent to which these alterations are cause or consequence of compromised organ function, and the underlying mechanisms in...
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Pharmacokinetics explain in vivo/in vitro discrepancies of carcinogen-induced gene expression alterations in rat liver and cultivated hepatocytes
Cultivated hepatocytes represent a well-established in vitro system. However, the applicability of hepatocytes in toxicogenomics is still controversially discussed. Recently, an in vivo/in vitro discrepancy ha...