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Toxicology Mechanisms and Methods

Masanori Horie, Kaori Shimizu, Yosuke Tabei
Metal oxide nanoparticles have an industrial value, although their harmful effects are also known. Induction of respiratory inflammation through their inhalation is a serious indicator of their toxicity. Although the phenomenon of metal ion release is involved in the induction of inflammation, all metal ions are not necessarily toxic. However, currently, no particular index to evaluate cytotoxicity caused by nanoparticles exists. An index based on biological response is critical. In the present study, we examined the gene expression-based index for nanoparticles-derived cytotoxicity...
June 8, 2018: Toxicology Mechanisms and Methods
Elnaz Mohammad Alizadeh, Majid Mahdavi, Forough Jenani Fard, Solmaz Chamani, Fereshteh Farajdokht, Pouran Karimi
Oxidative stress has a causative role in ischemic reperfusion-induced cell death. Evidence has shown that metformin is capable to reduce ischemic reperfusion injuries. The current study investigated the effect of metformin on ischemia/reperfusion-induced apoptosis in PC12 cells by evaluation of Bcl-2 family proteins expression. Cells were exposed to a time-dependent in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) injury and then treated with metformin. The intracellular reactive oxygen species (ROS) levels were measured...
June 7, 2018: Toxicology Mechanisms and Methods
Carlemi Calitz, Josias Hamman, Alvaro Viljoen, Stephen J Fey, Krzysztof Wrzesinski, Chrisna Gouws
Xysmalobium undulatum (Uzara) is one of the most widely used indigenous traditional herbal remedies in Southern Africa. Commercially available Uzara plant material was used to prepare a crude aqueous extract, of which the toxicity potential was investigated in the hepatic HepG2/C3A cell line in both traditional two-dimensional (2D) and rotating three-dimensional (3D) spheroid cell cultures. These cultures were treated over a period of 4 days at concentrations of 200, 350, 500, and 750 mg/kg plant extract to protein content...
June 6, 2018: Toxicology Mechanisms and Methods
Hiroki Yoshioka, Yoshimi Ichimaru, Shiori Fukaya, Akito Nagatsu, Tsunemasa Nonogaki
When multiple drugs or chemicals are used in combination, it is important to understand the risk of their interactions and predict potential additive effects. The aim of the current study was to investigate the molecular mechanism(s) accounting for the additive/synergistic effect of combination treatment with acetaminophen (APAP) and carbon tetrachloride (CCl4 ). Mice were intraperitoneally administered vehicle or 100 mg/kg (5 mL/kg) APAP and 30 min after vehicle or 15 mg/kg (5 mL/kg) CCl4 . Sixteen hours after treatment, mice from each group were sacrificed and the livers were removed...
June 6, 2018: Toxicology Mechanisms and Methods
Hadi Poorbagher, Hamed Ghaffari Farsani, Hamid Farahmand
DNA breakage has been frequently used as a biomarker of the pesticide toxicity. The present study introduced a method to quantify the DNA breakage in Oncorhynchus mykiss exposed to the pesticide Malathion. Specimens were exposed to different concentrations of malathion for 1-9 days and their gill and liver were sampled. DNA was extracted and electrophoresed using agarose gel. The pixel density curves were obtained from the gel smears. The area under the curves were arbitrarily divided from 3 up to 7 segments using a Java macro in the software ImageJ...
May 24, 2018: Toxicology Mechanisms and Methods
Hongying Liang, Tong He, Jimin Long, Liangliang Liu, Guochao Liao, Yanhuai Ding, Yi Cao
When entering a biological environment, proteins could be adsorbed onto nanoparticles (NPs), which will consequently influence the toxicity of NPs. This study used bovine serum albumin (BSA) as the model for serum protein and investigated its interactions with three different types of ZnO NPs, coded as XFI06 (pristine NPs of 20 nm), NM110 (pristine NPs of 100 nm) and NM111 (hydrophobic NPs of 130 nm). Atomic force microscope indicated the adsorption of BSA to ZnO NPs, leading to the increase of NP diameters...
May 21, 2018: Toxicology Mechanisms and Methods
Simona Latronico, Maria Elena Giordano, Emanuela Urso, Maria Giulia Lionetto, Trifone Schettino
Tris (1, 3-dichloro-2-propyl) phosphate (TDCPP) is one of the most diffused phosphorus flame retardants in the environment and is highly persistent and abundant in residential dust samples. To date the cellular targets and mechanisms underlying its toxic effects are not completely understood. The aim of this work was to study the effects of TDCPP on ion transport mechanisms fundamental for the cellular ionic homeostasis, such as Na+ -K+ -ATPase and Cl- transport. HeLa cells were used as experimental model. TDCPP showed a dose-dependent effect on cell viability in cells exposed for 24h as assessed by MTT test (IC50 = 52...
May 21, 2018: Toxicology Mechanisms and Methods
Olorunfemi R Molehin, Omotade I Oloyede, Stephen A Adefegha
White Butterfly (Clerodendrum volubile) leaf is commonly used in traditional medicine for the management of various diseases including diabetes without the full understanding of the scientific basis for its use. This study sought to evaluate the antihyperglycemic, antihyperlipidemic and antioxidant effect of Clerodendrum volubile leaves in streptozotocin (STZ)-induced diabetic rats. Aqueous extract of C. volubile was prepared and its effect assessed on relevant enzymes associated with diabetes. Fifty Male Wistar rats were randomly separated into ten groups each containing five rats...
May 21, 2018: Toxicology Mechanisms and Methods
Sen Zhang, Huan Chen, An Wang, Yong Liu, Hongwei Hou, Qingyuan Hu
To investigate the genotoxicity of gaseous toxicants CO and 1,3-butadiene in vitro, a novel combination technology-the in vitro γH2AX high content screening assay combined with air-liquid interface system was established. The results showed that this new technology was available and effective. Based on the joint technology, genotoxicity of CO and 1,3-butadiene was evaluated further in this study. The results showed that treatment concentrations (0, 20%,40%, 80% and 100%, v/v) and exposure time (15, 30, 45, 60 and 90 min) of CO both had no statistically significant effects on the induction of γH2AX (p > 0...
May 21, 2018: Toxicology Mechanisms and Methods
Emily N Dunn, Teresa M Ferrara-Bowens, Mark E Chachich, Cary L Honnold, Cristin C Rothwell, Heidi M Hoard-Fruchey, Catherine A Lesyna, Erik A Johnson, Douglas M Cerasoli, John H McDonough, C Linn Cadieux
Mice and other rodents are typically utilized for chemical warfare nerve agent research. Rodents have large amounts of carboxylesterase in their blood, while humans do not. Carboxylesterase non-specifically binds to and detoxifies nerve agent. The presence of this natural bioscavenger makes mice and other rodents poor models for studies identifying therapeutics to treat humans exposed to nerve agents. To obviate this problem, a serum carboxylesterase knockout (Es1 KO) mouse was created. In this study, Es1 KO and wild type (WT) mice were assessed for differences in gene expression, nerve agent (soman; GD) median lethal dose (MLD) values, and behavior prior to and following nerve agent exposure...
May 16, 2018: Toxicology Mechanisms and Methods
Christian Reuss Mikkelsen, Jakob Ross Jornil, Ljubica Vukelic Andersen, Jørgen Bo Hasselstrøm, Sebastian Polak
Methadone-related poisoning has been found to be the leading and increasing cause of death among intoxication cases in several countries. Aside from respiratory depression, methadone is known to cause QT-prolongation, which may lead to sudden cardiac death. Concentrations in heart tissue should be more accurate for estimating cardiotoxic effects. The aim of this study was to investigate whether the effect of methadone on the QT-interval could be simulated and whether the concentrations in heart tissues allowed for better prediction of the Bazett corrected QT-interval (QTcB)...
May 11, 2018: Toxicology Mechanisms and Methods
Marwa Hassen, Shadia M Kadry, Nawal Zakaria, Mai H El-Dakdoky
The present study was performed to investigate the role of bone marrow mesenchymal stem cells (MSCs) and/or melatonin (MT) for improvement of beta cell functions in STZ diabetic rats. Male albino rats (130-150g) were divided into six groups. CONTROL GROUP: received phosphate buffer saline (PBS); Melatonin group received melatonin (10 mg/kg b.wt./day for 2 months by oral gavage); Diabetic untreated group; Diabetic group treated with melatonin; Diabetic group treated with mesenchymal stem cells (A single intravenous injection of 3 × 106 cell in PBS) and Diabetic group co-treated with stem cells and melatonin...
May 1, 2018: Toxicology Mechanisms and Methods
Maryam Khoshkam, Yasamin Baghdadchi, Roghaye Arezumand, Ali Ramazani
Quantum dots (QDs) have widespread application in many fields such as medicine and electronics. The need for understanding the potentially harmful side effects of these materials becomes clear. In this study, the toxicity of cadmium telluride quantum dots (CdTe-QDs) and bulk Cd2+ has been investigated and compared by applying metabolomics methods. The datasets were 1 HNMR data from mice plasma which had been taken from four groups of mice in different time intervals. Then the data were analyzed by applying chemometrics methods and the metabolites were found from Human Metabolome Database (HMDB)...
April 30, 2018: Toxicology Mechanisms and Methods
Indumathi Dhananjayan, Kathiroli Sujithra, Srinivasan Subramani, Veerasamy Vinothkumar
This study hypothesized to evaluate the effect of betanin, a chromoalkaloid on plasma and altered tissues glycoprotein components in streptozotocin - nicotinamide induced diabetic rats. Diabetes was induced by a single intraperitoneal (i.p.) injection of streptozotocin (45 mg/kg b.w.) dissolved in 0.1 M citrate buffer (pH 4.5) 15 min after the i.p. administration of nicotinamide (110 mg/kg b.w.). Experimental rats were administered betanin at the dose of 20 mg/kg b.w. and glibenclamide (600µg/kg b...
April 30, 2018: Toxicology Mechanisms and Methods
Xianqiang Li, Xin Fang, Yanhuai Ding, Juan Li, Yi Cao
It is recently shown that biological macromolecules in food could interact with nanoparticles (NPs) and consequently change the biological effects of NPs. In this study, the interactions between ZnO NPs with or without hydrophobic surface coating and bovine serum albumin (BSA) or oleate complexed to BSA (OA-BSA) were assessed. Atomic force microscope showed topographic changes of both types of NPs by BSA or OA-BSA, which could indicate the formation of protein corona. ZnO NPs showed negative Zeta potential, which was slightly decreased by BSA or OA-BSA, with OA-BSA being more effective...
April 26, 2018: Toxicology Mechanisms and Methods
Heather A Lowers, G N Breit, M Strand, R M Pillers, G P Meeker, T I Todorov, G S Plumlee, R E Wolf, M Robinson, J Parr, R Miller, S Groshong, F Green, C Rose
Humans accumulate large numbers of inorganic particles in their lungs over a lifetime. Whether this causes or contributes to debilitating disease over a normal lifespan depends on the type and concentration of the particles. We developed and tested a protocol for in situ characterization of the types and distribution of inorganic particles in biopsied lung tissue from three human groups using field emission scanning electron microscopy (FE-SEM) combined with energy dispersive spectroscopy (EDS). Many distinct particle types were recognized among the 13 000 particles analyzed...
April 23, 2018: Toxicology Mechanisms and Methods
Mohammad Shokrzadeh, Atefeh Mirshafa, Niusha Yekta Moghaddam, Behnoosh Birjandian, Fatemeh Shaki
INTRODUCTION: Uncontrolled chronic hyperglycemia in diabetic patients could result in various complications, including neurotoxicity. Urtica dioica L. (UD) is known for its hypoglycemic and antioxidant effects. In this study, we evaluated the efficacy of UD and pioglitazone (PIO) in reduction of neurotoxicity and oxidative stress in streptozocin-induced diabetic mice. MATERIALS AND METHODS: Male mice were divided into seven groups: control, diabetic, dimethyl sulfoxide-treated control, PIO-treated, UD-treated, UD-PIO-treated, and vitamin E-treated...
April 18, 2018: Toxicology Mechanisms and Methods
Yi Wei, Yu Zhou, Xiang-Liang Tang, Bin Liu, Lian-Ju Shen, Chun-Lan Long, Tao Lin, Da-Wei He, Sheng-de Wu, Guang-Hui Wei
BACKGROUND: Cryptorchidism is a common condition of childhood, and it is known to impair fertility potential. However, the underlying mechanisms remain unclear. METHODS: This study constructed two cryptorchid rat models to investigate the roles of apoptosis and autophagy in testicular impairment induced by cryptorchidism. Pregnant rats were randomly divided into three groups. Group I: non-treated rats were used as controls. Group II: injected with drug Flutamide (Flu) 25 mg/kg/bw/d from Gestation Day (GD) 11-19...
April 2, 2018: Toxicology Mechanisms and Methods
Jayme P Coyle, Robert J Rinaldi, Giffe T Johnson, Marie M Bourgeois, James D McCluskey, Raymond D Harbison
Acrolein is a reactive electrophilic aldehyde known to cause mitochondrial dysfunction, oxidative stress, and dysregulation of signaling transduction in vitro. Most in vitro systems employ standard cell culture maintenance conditions of 95% air/5% CO2 , translating to a culture oxygen tension of approximately 20%, far above most physiological tissues. The purpose of this investigation was to examine whether low-serum, retinoic acid differentiated H9c2 cells were less sensitive to acrolein insult when cultured under reduced oxygen tension...
March 22, 2018: Toxicology Mechanisms and Methods
Paulina Natalia Kopa, Rafał Pawliczak
Cigarette smoke has a crucial impact on transcriptome alteration by its effect on chromatin remodeling and DNA methylation status. The first mechanism is associated with the histone acetylation/deacetylation balance damage as a result of increased activity of NFĸB and lipid peroxidation products, which lead to an increased activity of HATs and DNMTs and reduced HDACs. The second mechanism is connected with direct damaging of DNA by smoke components, activation of downstream repair mechanism and recruitment of DNMTs into the breakage site, 'nicotine effect' and carbon monoxide (CO) activity on gene transcription and DNA methylation reduction...
July 2018: Toxicology Mechanisms and Methods
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