Toxicology in Vitro : An International Journal Published in Association with BIBRA

INTRODUCTION: Statins have demonstrated chondroprotective effects by reducing inflammation and mitigating extracellular matrix degradation. However, statins are also reported to be cytotoxic to several types of cells. Early-onset osteoarthritis (OA) is characterized by synovial inflammation, which adversely affects hyaluronan (HA) production in fibroblast-like synoviocytes (FLSs). Nevertheless, the precise effects of statins on the synovium remain unclear. METHODS: This study investigated the impact of lovastatin on human FLSs, and HA secretion-related genes, signaling pathways, and production were evaluated...

Dexamethasone (DEX) is a synthetic glucocorticoid widely used as pharmaceutical and usually exists in effluents with varying degrees of concentrations. In this study, cultivated Brain, ovary and testis cells from Arabian Sea bream, Acanthopagrus arabicus, were treated by DEX at concentrations of 0, 0.3, 3.0, 30.0 and 300.0 μg/ml for 48 h. The aromatase activity and steroid (17-β-estradiol (E2), progesterone (P) and testosterone (T)) production by cells were measured at 12, 24 and 48 h of the experiment...

BACKGROUND: An etiology of palmitic acid (PA) induced insulin resistance (IR) is complex for which two mechanisms are proposed namely ROS induced JNK activation and lipid induced protein kinase-C (PKCε) activation. However, whether these mechanisms act alone or in consortium is not clear. METHODS AND RESULTS: In this study, we have characterized PA induced IR in liver cells. These cells were treated with different concentrations of PA for either 8 or 16 h...

To combat opioid abuse, the U.S. Food and Drug Administration (FDA) released a comprehensive action plan to address opioid addiction, abuse, and overdose that included increasing the prevalence of abuse-deterrent formulations (ADFs) in opioid tablets. Polyethylene oxide (PEO) has been widely used as an excipient to deter abuse via nasal insufflation. However, changes in abuse patterns have led to unexpected shifts in abuse from the nasal route to intravenous injection. Case reports identify adverse effects similar to thrombotic thrombocytopenic purpura (TTP) syndrome following the intravenous (IV) abuse of opioids containing PEO excipient...

BACKGROUND: CircRNAs are implicated in the tumorigenesis of various human cancers. This study aims to explore how circ_0003356 contributes to the development of gastric cancer (GC). METHODS: Circ_0003356 expression was analyzed in GSE184882 dataset and validated in our cohort of GC patients and human GC cell lines. The correlations between circ_0003356 levels and prognostic parameters were analyzed. The contribution of circ_0003356 in GC cell malignant behaviors such as cell survival, apoptosis and invasion were investigated by circ_0003356 overexpression in GC cell lines...

The objective of Safe-by-Design (SbD) is to support the development of safer products and production processes, and enable safe use throughout a materials' life cycle; an intervention at an early stage of innovation can greatly benefit industry by reducing costs associated with the development of products later found to elicit harmful effects. Early hazard screening can support this process, and is needed for all of the expected nanomaterial exposure routes, including inhalation, ingestion and dermal. In this study, we compare in vitro and ex vivo cell models that represent dermal exposures (including HaCaT cells, primary keratinocytes, and reconstructed human epidermis (RhE)), and when possible consider these in the context of regulatory accepted OECD TG for in vitro dermal irritation...

Natural products and their biological activities are currently a subject of great interest to the industrial and scientific sector, due to society's awareness of the proper use of biodiversity and economic and sustainability. To promote the sustainable use of biomass the extract of the by-product of the shell seed of Lecythis pisonis was applied to develop a natural cosmetic emulsion. To ensure safety for its topical use the cytotoxic activity of its crude extract was evaluated by the colorimetric method of 3- bromide (4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium, MTT, in cell culture of fibroblasts L929, human keratinocytes HaCat, and human endothelium EA...

Here we evaluated the gill epithelial cell line ASG-10 from Atlantic salmon, as an in vitro model for research on known water quality challenges in aquaculture. Ammonia/ammonium (NH3 /NH4 + ), a recognized challenge in water-intensive recirculating aquaculture systems (RAS), induced lysosomal vacuolization, reduced protein degradation and cell migration of the ASG-10 cells. Aluminium (Aln+ ), another challenge in freshwater aquaculture facilities had only minor effects. Next, we investigated the tolerance for direct water exposure of ASG-10...

Zearalenone (ZEN) is a mycoestrogen produced by Fusarium fungi. ZEN is a frequent contaminant in cereal-based products, representing significant health threat. The major reduced metabolites of ZEN are α-zearalenol (α-ZEL) and β-zearalenol (β-ZEL). Since the toxicokinetic interactions of ZEN/ZELs with cytochrome P450 enzymes (CYPs) and organic anion transporting polypeptides (OATPs) have been barely characterized, we examined these interactions applying in vitro models. ZEN and ZELs were relatively strong inhibitors of CYP3A4 and moderate inhibitors of CYP1A2 and CYP2C9...

Nucleosides and nucleotides at μM concentrations stimulated a 300% increase in acid secretion in HepG2 cells, which was quantitatively accounted for as increased export of lactate generated by glycogenolysis. Agonist selectivity encompassed nucleosides and nucleotides for all 5 natural nucleobases and, along with antagonist profiles, was inconsistent with a role for purinergic receptors in mediating this activity. Agonist catabolism did not contribute significantly to either low selectivity or lactate production...

Gliomas are among the most common primary malignant brain tumors. Despite advances in cancer treatment, survival is very low, so the discovery of new therapeutic agents is essential. In this context, indole is an important source for the development of new bioactive molecules. A pharmacological screening of ten indole derivatives was carried out to evaluate the cytotoxic capacity against three tumor cell lines. After pharmacological screening, three compounds were selected, based on their high capacity to reduce cell proliferation, and their IC50 values were determined...

Arsenic compounds are common environmental toxicants worldwide and particularly enriched in the Northeast and the Southwestern United States, the Alps, and Bangladesh. Exposure to arsenic is linked with various detrimental health outcomes, including cancer, cognitive decline, and kidney damage. Our group has previously shown that arsenic trioxides alter T cell cytokine production. In the current study, we demonstrate that exposure to arsenic compounds alters B cell function in an in vitro influenza model. Human peripheral blood mononuclear cells (PBMCs) were isolated from blood and cultured with arsenic trioxide (As3 O2 ) and subsequently challenged with Influenza A virus...

Secondary metabolites from medicinal plants have a well-established therapeutic potential, with many of these chemicals having specialized medical uses. Isoflavonoids, a type of secondary metabolite, have little cytotoxicity against healthy human cells, making them interesting candidates for cancer treatment. Extensive research has been conducted to investigate the chemo-preventive benefits of flavonoids in treating various cancers. Biochanin A (BA), an isoflavonoid abundant in plants such as red clover, soy, peanuts, and chickpeas, was the subject of our present study...

Estrogen-induced intrahepatic cholestasis (IHC) is a mild but potentially serious risk and urges for new therapeutic targets and effective treatment. Our previous study demonstrated that RORγt and CXCR3 signaling pathway of invariant natural killer T (iNKT) 17 cells play pathogenic roles in 17α-ethinylestradiol (EE)-induced IHC. Ursodeoxycholic acid (UDCA) and 18β-glycyrrhetinic acid (GA) presents protective effect on IHC partially due to their immunomodulatory properties. Hence in present study, we aim to investigate the effectiveness of UDCA and 18β-GA in vitro and verify the accessibility of the above targets...

OBJECTIVE: Endoplasmic reticulum (ER) stress mediates Cd-caused germ cell apoptosis in testis. The effects of 4-phenylbutyric acid (PBA), a classical chaperone, were investigated on Cd-induced apoptosis in mouse GC-1 spermatogonia cells. METHODS: The cells were pretreated with PBA before Cd exposure. TUNEL and flow cytometry assays were applied to determine apoptosis. Some key biomarkers of ER stress were analyzed using RT-PCR and western blot. RESULTS: as expected, the apoptotic cells exposed to Cd apparently increased...

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Iron oxide of various structures is frequently used as food colorant (E 172). The spectrum of colors ranges from yellow over orange, red, and brown to black, depending on the chemical structure of the material. E 172 is mostly sold as solid powder. Recent studies have demonstrated the presence of nanoscaled particles in E 172 samples, often to a very high extent. This makes it necessary to investigate the fate of these particles after oral uptake. In this study, 7 differently structured commercially available E 172 food colorants (2 x Yellow FeO(OH), 2 x Red Fe2 O3 , 1 x Orange Fe2 O3  + FeO(OH) and 2 x Black Fe3 O4 ) were investigated for particle dissolution, ion release, cellular uptake, crossing of the intestinal barrier and toxicological impact on intestinal cells...

The use of fetal bovine serum (FBS) in cell culture is being questioned for scientific and ethical reasons, prompting the exploration of alternative approaches. Nevertheless, the influence of FBS on cell functioning, especially in fish cells, has not been comprehensively examined. This study aims to evaluate the impact of FBS on the lipidome of PLHC-1 spheroids and investigate cellular and molecular responses to plastic additives in the presence/absence of FBS. Lipidomic analyses were conducted on PLHC-1 cell spheroids using liquid chromatography coupled with a high-resolution quadrupole time-of-flight mass spectrometer (HRMS-QToF)...

Early neurodevelopmental processes are strictly dependent on spatial and temporally modulated of thyroid hormone (TH) availability and action. Thyroid hormone transmembrane transporters (THTMT) are critical for regulating the local concentrations of TH, namely thyroxine (T4) and 3,5,3'-tri-iodothyronine (T3), in the brain. Monocarboxylate transporter 8 (MCT8) is one of the most prominent THTMT. Genetically induced deficiencies in expression, function or localization of MCT8 are associated with irreversible and severe neurodevelopmental adversities...

Fragrances can cause allergic skin reactions, expressed as allergic contact dermatitis and reactions in the respiratory tract that range from acute temporary upper airway irritation to obstructive lung disease. These adverse health effects may result from the stimulation of a specific (adaptive) immune response. Th1 cells, which essentially produce interleukin-2 (IL-2) and interferon-γ (IFN-γ), play a key role in allergic contact dermatitis and also on allergic sensitization to common allergens (e...