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Toxicology Research

Harriet Gaskell, Parveen Sharma, Helen E Colley, Craig Murdoch, Dominic P Williams, Steven D Webb
More predictive in vitro liver models are a critical requirement for preclinical screening of compounds demonstrating hepatotoxic liability. 3D liver spheroids have been shown to have an enhanced functional lifespan compared to 2D monocultures; however a detailed characterisation of spatiotemporal function and structure of spheroids still needs further attention before widespread use in industry. We have developed and characterized the structure and function of a 3D liver spheroid model formed from C3A hepatoma cells...
June 1, 2016: Toxicology Research
Crystal S Lewis, Luisa Torres, Jeremy T Miyauchi, Cyrus Rastegar, Jonathan M Patete, Jacqueline M Smith, Stanislaus S Wong, Stella E Tsirka
Understanding the nature of interactions between nanomaterials, such as commercially ubiquitous hematite (α-Fe2O3) Nanorhombohedra (N-Rhomb) and biological systems is of critical importance for gaining insight into the practical applicability of nanomaterials. Microglia represent the first line of defense in the central nervous system (CNS) during severe injury or disease such as Parkinson's and Alzheimer's disease as illustrative examples. Hence, to analyze the potential cytotoxic effect of nanorhombohedra exposure in the presence of microglia, we have synthesized Rhodamine B (RhB) labeled-α-Fe2O3 N-Rhomb, with lengths of 47 ± 10 nm and widths of 35 ± 8 nm...
May 1, 2016: Toxicology Research
Xiaoren Tang, Salomon Amar
Kavain, an extract from the shrub Piper Methysticum, was recently reported to modulate TNF-α expression in both human and mouse cells via regulation of LPS-Induced TNF-Alpha Factor (LITAF). The purpose of the present study was to define the molecular pathway(s) associated with Kavain effects on TNF modulation. In vitro studies using WT mouse primary macrophages showed that Kavain significantly reduced E.coli LPS-induced TNF-α production but this effect was almost abrogated in LITAF(-/-) and ERK2(-/-) cells...
January 1, 2016: Toxicology Research
Patricia Erebi Tawari, Zhipeng Wang, Mohammad Najlah, Chi Wai Tsang, Vinodh Kannappan, Peng Liu, Christopher McConville, Bin He, Angel L Armesilla, Weiguang Wang
The anticancer activity of disulfiram (DS) is copper(ii) (Cu)-dependent. This study investigated the anticancer mechanisms of DS/Cu using in vitro cytotoxicity and metabolic kinetic analysis. Our study indicates that DS/Cu targets cancer cells by the combination of two types of actions: (1) instant killing executed by DS/Cu reaction generated reactive oxygen species; (2) delayed cytotoxicity introduced by the end product, DDC-Cu. Nanoencapsulation of DS might shed light on repositioning of DS into cancer treatment...
November 19, 2015: Toxicology Research
S AlGhamdi, V Leoncikas, K E Plant, N J Plant
There has been a dramatic increase in the number of clinically obese individuals in the last twenty years. This has resulted in an increasingly common scenario where obese individuals are treated for other diseases, including cancer. Here, we examine interactions between lipid-induced steatosis and doxorubicin treatment in the human hepatoma cell line Huh7. The response of cells to either doxorubicin, lipid-loading or a combination were examined at the global level by DNA microarray, and for specific endpoints of cytotoxicity, lipid-loading, reactive oxygen species, anti-oxidant response systems, and apoptosis...
November 19, 2015: Toxicology Research
S Meyer, G Raber, F Ebert, L Leffers, S M Müller, M S Taleshi, K A Francesconi, T Schwerdtle
Arsenic-containing fatty acids are a group of fat-soluble arsenic species (arsenolipids) which are present in marine fish and other seafood. Recently, it has been shown that arsenic-containing hydrocarbons, another group of arsenolipids, exert toxicity in similar concentrations comparable to arsenite although the toxic modes of action differ. Hence, a risk assessment of arsenolipids is urgently needed. In this study the cellular toxicity of a saturated (AsFA 362) and an unsaturated (AsFA 388) arsenic-containing fatty acid and three of their proposed metabolites (DMA(V), DMAPr and thio-DMAPr) were investigated in human liver cells (HepG2)...
September 18, 2015: Toxicology Research
D P Jackson, A D Joshi, C J Elferink
The Ah receptor is a transcription factor that modulates gene expression via interactions with multiple protein partners; these are reviewed, including the novel NC-XRE pathway involving KLF6.
September 1, 2015: Toxicology Research
Byeong Hwa Yun, Viktoriya S Sidorenko, Thomas A Rosenquist, Kathleen G Dickman, Arthur P Grollman, Robert J Turesky
Aristolochic acids (AA) are found in all Aristolochia herbaceous plants, many of which have been used worldwide for medicinal purposes for centuries. AA are causal agents of the chronic kidney disease entity termed aristolochic acid nephropathy (AAN) and potent upper urinary tract carcinogens in humans. AAN and upper urinary tract cancers are endemic in rural areas of Croatia and other Balkan countries where exposure to AA occurs through the ingestion of home-baked bread contaminated with Aristolochia seeds...
July 1, 2015: Toxicology Research
Jingcheng Xiao, Qi Wang, Kristin M Bircsak, Xia Wen, Lauren M Aleksunes
The BCRP (ABCG2) transporter is responsible for the efflux of chemicals from the placenta to the maternal circulation. Inhibition of BCRP activity could enhance exposure of offspring to environmental chemicals leading to altered reproductive, endocrine, and metabolic development. The purpose of this study was to characterize environmental chemicals as potential substrates and inhibitors of the human placental BCRP transporter. The interaction of BCRP with a panel of environmental chemicals was assessed using the ATPase and inverted plasma membrane vesicle assays as well as a cell-based fluorescent substrate competition assay...
May 1, 2015: Toxicology Research
Patrick Allard
Toxicology has seen a recent influx of new talents from other fields attracted by the application of their expertise to pressing questions of toxicological and environmental relevance. This transition has opened the door to innovative and exciting scientific opportunities but has also generated a new set of questions and challenges. In this viewpoint article, I will highlight some of the drivers and hurdles encountered by the recent new breeds of toxicologists.
May 1, 2015: Toxicology Research
Daniela A Parodi, Jasmine Sjarif, Yichang Chen, Patrick Allard
The comprehensive identification and mechanistic analysis of reproductive toxicants constitutes one of the major hurdles in the toxicological assessment of chemicals originating from the large number of chemicals to be tested and the difficulty in examining germ cells at various stages of their development. We previously described the development of an assay in the roundworm Caenorhabditis elegans that allows the detection of chemicals bearing aneugenic activity and that could be used for the detection of germline toxicity...
May 2015: Toxicology Research
Chibuzor Uchea, Stewart F Owen, J Kevin Chipman
Prediction of xenobiotic fate in fish is important for the regulatory assessment of chemicals under current legislation. Trout hepatocyte spheroids are a promising in vitro model for this assessment. In this investigation, the gene expression and function for xenobiotic metabolism and cellular efflux were characterised. Using fluorescence, transport and real time PCR analysis, the expression and functionality of a variety of genes related to xenobiotic metabolism and drug efflux were assessed in a range of trout hepatocyte culture preparations...
March 23, 2015: Toxicology Research
Pan Chen, Sudipta Chakraborty, Tanara V Peres, Aaron B Bowman, Michael Aschner
Manganese (Mn) is one of the most abundant metals on the earth. It is required for normal cellular activities, but overexposure leads to toxicity. Neurons are more susceptible to Mn-induced toxicity than other cells, and accumulation of Mn in the brain results in Manganism that presents with Parkinson's disease (PD)-like symptoms. In the last decade, a number of Mn transporters have been identified, which improves our understanding of Mn transport in and out of cells. However, the mechanism of Mn-induced neurotoxicity is only partially uncovered, with further research needed to explore the whole picture of Mn-induced toxicity...
March 1, 2015: Toxicology Research
Rabbab Oun, Rafael S Floriano, Lyle Isaacs, Edward G Rowan, Nial J Wheate
The cucurbituril family of drug delivery vehicles have been examined for their tissue specific toxicity using ex vivo models. Cucurbit[6]uril (CB[6]), cucurbit[7]uril (CB[7]) and the linear cucurbituril-derivative Motor2 were examined for their neuro-, myo- and cardiotoxic activity and compared with β-cyclodextrin. The protective effect of drug encapsulation by CB[7] was also examined on the platinum-based anticancer drug cisplatin. The results show that none of the cucurbiturils have statistically measurable neurotoxicity as measured using mouse sciatic nerve compound action potential...
November 1, 2014: Toxicology Research
Maria Mrakovcic, Claudia Meindl, Eva Roblegg, Eleonore Fröhlich
Nanoparticles (NPs) are increasingly used in industrial, health and consumer products. In addition to the intended effects, NPs may also cause cell damage. Typical cytotoxicity assays assess short-term effects in adherent cells but do not evaluate longer exposure times and do not focus on cells in suspension. Since NPs are not removed easily from the organism, non-biodegradable NPs may persist in the systemic circulation and affect monocyte function at low concentrations. To mimic this situation, THP-1 monocytes were exposed to low concentrations of plain polystyrene particles (PPP) in different sizes for short (24 h) and prolonged (16 d) time periods...
March 1, 2014: Toxicology Research
Shenmin Pan, Naimish P Sardesai, Hongyun Liu, James F Rusling
Peroxidase enzyme digests of oxidized single-wall carbon nanotubes (SWCNT) were shown to damage DNA in potentially genotoxic reactions for the first time using an electro-optical array with and without metabolic activation.
November 1, 2013: Toxicology Research
Tracie Perkins Fullove, Hongtao Yu
Polycyclic aromatic hydrocarbons (PAHs), a class of mutagenic environmental contaminants, insert toxicity through both metabolic activation and light irradiation. Pyrene, one of the most widely studied PAHs, along with its mono-substituted derivatives, 1-amino, 1-bromo, 1-hydroxy, and 1-nitropyrene, were chosen to study the effect of substituents on their phototoxicity, DNA damage and repair. Both alkaline Comet assay, which detects direct DNA damages, and Fpg endonuclease Comet assay, which detects oxidative DNA damages, were conducted at 0, 2, 4, 8, and 24 h of incubation of the cells in minimal growth medium after concomitant exposure to pyrene derivatives and UVA light...
May 1, 2013: Toxicology Research
Gregory P Dooley, Ronald B Tjalkens, William H Hanneman
The primary metabolite of the herbicide atrazine (ATRA), diaminochlorotriazine (DACT), has been suggested to cause disruption in the hypothalamic-pituitary-gonadal axis leading to inhibition of luteinizing hormone (LH) release. DACT is a reactive electrophile known to form covalent protein adducts both in vitro and in vivo following ATRA exposure and maybe targeting proteins involved in GnRH-induced calcium signaling and subsequent LH release. To test this hypothesis, LβT2 pituitary cells were exposed to 300 μM DACT for 24 hrs and examined by fluorescence microscopy for GnRH-induced changes in intracellular calcium and LH release...
May 1, 2013: Toxicology Research
April P Neal, Tomas R Guilarte
Human exposure to neurotoxic metals is a global public health problem. Metals which cause neurological toxicity, such as lead (Pb) and manganese (Mn), are of particular concern due to the long-lasting and possibly irreversible nature of their effects. Pb exposure in childhood can result in cognitive and behavioural deficits in children. These effects are long-lasting and persist into adulthood even after Pb exposure has been reduced or eliminated. While Mn is an essential element of the human diet and serves many cellular functions in the human body, elevated Mn levels can result in a Parkinson's disease (PD)-like syndrome and developmental Mn exposure can adversely affect childhood neurological development...
March 1, 2013: Toxicology Research
Dominic P Williams, Rebecca Shipley, Marianne J Ellis, Steve Webb, John Ward, Iain Gardner, Stuart Creton
The focus of much scientific and medical research is directed towards understanding the disease process and defining therapeutic intervention strategies. The scientific basis of drug safety is very complex and currently remains poorly understood, despite the fact that adverse drug reactions (ADRs) are a major health concern and a serious impediment to development of new medicines. Toxicity issues account for ∼21% drug attrition during drug development and safety testing strategies require considerable animal use...
January 1, 2013: Toxicology Research
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