Toxicology

Aryl hydrocarbon receptor-dependent regulation of miR-196a expression controls lung fibroblast apoptosis but not proliferation
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor implicated in the regulation of apoptosis and proliferation. Although activation of the AhR by xenobiotics such as dioxin inhibits the cell cycle and control apoptosis, paradoxically, AhR expression also promotes cell proliferation and survival independent of exogenous ligands. The microRNA (miRNA) miR-196a has also ...


Biodistribution and toxicological study of PEGylated single-wall carbon nanotubes in the zebrafish (Danio rerio) nervous system
Nanotechnology has been proven to be increasingly compatible with pharmacological and biomedical applications. Therefore, we evaluated the biological interactions of single-wall carbon nanotubes functionalized with polyethylene glycol (SWNT-PEG). For this purpose, we analyzed biochemical, histological, behavioral and biodistribution parameters to understand how this material behaves in vitro an...
Upregulation of heme oxygenase-1 expression by dehydrodiconiferyl alcohol (DHCA) through the AMPK–Nrf2 dependent pathway
Oxidative stress is induced by the accumulation of free radicals, resulting in an imbalanced cellular redox state, which has been implicated in a variety of human diseases. Dehydrodiconiferyl alcohol (DHCA), a lignan compound isolated from Cucurbita moschata, has previously been reported to contain anti-adipogenic and anti-lipogenic effects on 3T3-L1 cells and primary MEFs. In this study, it wa...


Involvement of Endoplasmic Reticulum Stress in All-trans-retinal Induced Retinal Pigment Epithelium Degeneration
Excess accumulation of endogenous all-trans-retinal (atRAL) contributes to degeneration of the retinal pigment epithelium (RPE) and photoreceptor cells, and plays a role in the etiologies of age-related macular degeneration (AMD) and Stargardt's disease. In this study, we reveal that human RPE cells tolerate exposure of up to 5 μM atRAL without deleterious effects, but higher concentrations ...
Efficacy of Active Carbon towards the Absorption of Deoxynivalenol in Pigs
In order to assess the in vivo efficacy of mycotoxin binders, specific toxicokinetic parameters should be measured according to European guidelines. For this purpose, an absorption model in pigs is described with emphasis on absorption kinetics. Pigs received a single oral bolus of the mycotoxin deoxynivalenol alone or in combination with active carbon (applied as mycotoxin binder). After admin...


Biokinetics and effects of barium sulfate nanoparticles
Nanoparticulate barium sulfate has potential novel applications and wide use in the polymer and paint industries. Only a short-term inhalation study on barium sulfate nanoparticles (BaSO4 NPs) has been published [Part Fibre Toxicol 11:16, 2014]. We performed comprehensive biokinetic studies of 131BaSO4 NPs administered via different routes and of acute and subchronic pulmonary responses to inst...
Proteomic analysis of changes in the protein composition of MCF-7 human breast cancer cells induced by all-trans retinoic acid, 9-cis retinoic acid, and their combination
Retinoic acid (all-trans and 9-cis) isomers represent important therapeutic agents for many types of cancers, including human breast cancer. Changes in protein composition of the MCF-7 human breast cancer cells were induced by all-trans retinoic acid, 9-cis retinoic acid, and their combination and subsequently proteomic strategies based on bottom-up method were applied. Proposed approach was us...

Screening of a chemical library reveals novel PXR-activating pharmacologic compounds
The pregnane X receptor (PXR) is one of the master regulators of xenobiotic transformation. Interactions between pharmacologic compounds and PXR frequently result in drug-to-drug interactions, drug-induced hepatotoxicity, and the development of drug-resistant phenotypes in cancer cells. Potential PXR-mediated effects on drug metabolism can be predicted using high-throughput methods to detect PX...
Firefighters’ exposure to perfluoroalkyl acids and 2-butoxyethanol present in firefighting foams
The aim of this study was to assess eight firefighters’ exposure to Sthamex 3% AFFF (aqueous film forming foam) in the simulation of aircraft accidents at Oulu airport in Finland. Study was conducted in 2010 before limitation for the use of PFOA and PFOS in AFFFs. Due to prospective limitation also eight commercially available AFFFs were evaluated from occupational and environmental point of ...

Liver DNA methylation analysis in adult female C57BL/6JxFVB mice following perinatal exposure to bisphenol A exposure
Bisphenol A (BPA) is a compound released from plastics and other consumer products used in everyday life. BPA exposure early in fetal development is proposed to contribute to programming of chronic diseases like obesity and diabetes, by affecting DNA methylation levels. Previously, we showed that in utero and lactational exposure of C57BL/6JxFVB hybrid mice via maternal feed using a dose range ...
Species- and congener-differences in microcystin-LR and -RR GSH conjugation in human, rat, and mouse hepatic cytosol
The accepted pathway for MC biotransformation is GSH conjugation, occurring either spontaneously or catalyzed by GST. In the present work, the already available information on human MC metabolism have been expanded and the capacity of human GST to conjugate MC-LR has been confirmed in human liver cytosol. At physiological GSH content the spontaneous reaction predominated on the enzymatic one; t...

Diet supplementation with cholic acid promotes intestinal epithelial proliferation in rats exposed to γ-radiation
Consumption of a high-fat diet increases some secondary bile acids (BAs) such as deoxycholic acid (DCA) in feces. DCA is derived from cholic acid (CA), a primary BA. We evaluated intestinal epithelial proliferation and BA metabolism in response to oral administration of cholic acid (CA) in rats to determine the influence of a CA diet on the responses of gut epithelia to γ-rays. WKAH/HkmSlc rat...
Phenylbutyric acid inhibits epithelial-mesenchymal transition during bleomycin-induced lung fibrosis
A recent report showed that unfolded protein response (UPR) signaling was activated during bleomycin (BLM)-induced pulmonary fibrosis. Phenylbutyric acid (PBA) is an endoplasmic reticulum (ER) chemical chaperone that inhibits the UPR signaling. The present study investigated the effects of PBA on BLM-induced epithelial-mesenchymal transition (EMT) and pulmonary fibrosis. For induction of pulmon...
Role of cytochrome P450-mediated metabolism and identification of novel thiol-conjugated metabolites in mice with phenytoin-induced liver injury
Phenytoin, 5,5-diphenylhydantoin (DPH), is widely used as an anticonvulsant agent. Severe hepatic injury rarely occurs in patients who received DPH. The development of liver injury is thought to be caused by reactive metabolites; however, the metabolites suggested to contribute to hepatotoxicity have not yet been detected in vivo and their effect on developing the liver injury is largely unknow...
Uptake and elimination of permethrin related to the use of permethrin treated clothing for forestry workers
Wearing of permethrin treated clothing usually implicates an uptake of permethrin by the user. of our study was to examine the kinetics of internal permethrin exposure in volunteers during and after a single 8h-use of treated clothing as well as factors potentially influencing permethrin uptake. 28 male volunteers (age: 20–34 years) were equipped with permethrin treated jackets and pants from...