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Cytotoxic exposure

Javier Conde-Vancells, Mercedes Vazquez-Chantada, Catherine W McCollum, Maria Bondesson, Sharanya Maanasi Kalasekar, Bogdan J Wlodarczyk, Jan-Åke Gustafsson, Robert M Cabrera, Richard H Finnell
In this study we combine assays using mouse embryonic stem cells (mESCs) and zebrafish embryos to evaluate the potential developmental toxicity of industrial and pharmaceutical chemicals. A set of eleven chemicals of known mammalian in vivo teratogenicity were tested in the assays and correlations to mammalian data investigated. Using mESCs, proliferation, differentiation, and cytotoxicity of the chemicals were measured. In zebrafish embryos, lethality and the lowest effect level concentrations for morphological malformations were determined...
August 10, 2018: Reproductive Toxicology
Benigno C Valdez, Xiaowen Tang, Yang Li, David Murray, Yan Liu, Uday Popat, Richard E Champlin, Borje S Andersson
The combination of DNA alkylating agents busulfan (Bu) and cyclophosphamide is the most commonly used myeloablative pre-transplant conditioning therapy for myeloid leukemias. However, it is associated with significant non-relapse mortality, which prohibits dose-escalation to control relapse. We hypothesized that combining these two drugs with an epigenetic modifier would increase anti-leukemic efficacy without jeopardizing patient safety. A pre-clinical study was performed to determine the synergistic cytotoxicity of Bu, 4-hydroperoxycyclophosphamide (4HC) and the hypomethylating agent decitabine (DAC) in human AML cell lines...
August 10, 2018: Experimental Hematology
Indre Graunaite, Greta Lodiene, Odeta Arandarcikaite, Audrius Pukalskas, Vita Machiulskiene
This in vitro study aimed to detect leaching components from an epoxy resin- and a methacrylate-based endodontic sealer and correlate them to cytotoxicity induced by material extracts for up to 36 weeks. We qualitatively determined the substances released by aged AH Plus and RealSeal SE specimens at seven intervals between 0 and 36 weeks. Quantification was performed by ultra-performance liquid chromatography/mass spectrometry (UPLC/MS). We determined the viability of murine macrophage J774 cells after 24 h exposure to material extracts, at each interval, using a fluorescence staining/microscopy method...
August 12, 2018: Journal of Oral Science
Seham Skah, Nina Richartz, Eva Duthil, Karin M Gilljam, Christian Bindesbøll, Elin Hallan Naderi, Agnete B Eriksen, Ellen Ruud, Marta M Dirdal, Anne Simonsen, Heidi Kiil Blomhoff
Autophagy is important in regulating the balance between cell death and survival, with the tumor suppressor p53 as one of the key components in this interplay. We have previously utilized an in vitro model of the most common form of childhood cancer, B cell precursor acute lymphoblastic leukemia (BCP-ALL), to show that activation of the cAMP signaling pathway inhibits p53-mediated apoptosis in response to DNA damage in both cell lines and primary leukemic cells. The present study reveals that cAMP-mediated survival of BCP-ALL cells exposed to DNA damaging agents, involves a critical and p53-independent enhancement of autophagy...
July 13, 2018: Oncotarget
Marzieh Zeinvand-Lorestani, Heibatullah Kalantari, Mohammad Javad Khodayar, Ali Teimoori, Najmaldin Saki, Akram Ahangarpour, Fakher Rahim, Soheila Alboghobeish
The key features of type 2 diabetes mellitus (T2DM) caused by high fat diet (HFD) in combination with arsenic (As) exposure (pronounced glucose intolerance despite a significant decrease in insulin resistance) are different from those expected for T2DM. Autophagy has been considered as a possible link between insulin resistance and obesity. Therefore in this study, we utilized autophagy gene expression profiling via real-time RT-PCR array analysis in livers of NMRI mice exposed to an environmentally relevant and minimally cytotoxic concentration of arsenite (50 ppm) in drinking water while being fed with a HFD for 20 weeks...
August 10, 2018: Scientific Reports
Noora Ottman, Lasse Ruokolainen, Alina Suomalainen, Hanna Sinkko, Piia Karisola, Jenni Lehtimäki, Maili Lehto, Ilkka Hanski, Harri Alenius, Nanna Fyhrquist
BACKGROUND: Sufficient exposure to natural environments, in particular soil and its microbes, has been suggested to be protective against allergies. OBJECTIVE: We aim at gaining more direct evidence of the environment-microbiota-health axis by studying the colonization of gut microbiota in mice after exposure to soil and by examining immune status in both a steady-state situation and during allergic inflammation. METHODS: The gastrointestinal microbiota of mice housed on clean bedding or in contact with soil was analyzed by using 16S rRNA gene sequencing, and the data were combined with immune parameters measured in the gut mucosa, lung tissue, and serum samples...
July 31, 2018: Journal of Allergy and Clinical Immunology
Bruna Taciane da Silva Bortoleti, Manoela Daiele Gonçalves, Fernanda Tomiotto-Pellissier, Milena Menegazzo Miranda-Sapla, João Paulo Assolini, Amanda Cristina Machado Carloto, Priscila Goes Camargo de Carvalho, Ian Lucas Alves Cardoso, Andréa Name Colado Simão, Nilton Syogo Arakawa, Idessania Nazareth Costa, Ivete Conchon-Costa, Wander Rogério Pavanelli
BACKGROUND: American tegumentary leishmaniasis (ATL) is a zoonotic disease caused by protozoa of the genus Leishmania. The high toxicity, high costs and resistance of some strains to current drugs has prompted the search for therapeutic alternatives for the management of this disease. Sphagneticola trilobata is a plant that has diterpenes as main constituents, including grandiflorenic acid (GFA) that has antiinflammatory, antiprotozoal, antibacterial and antinociceptive activity. PURPOSE: The aim of our study was to determine the effect of GFA on both the promastigotes and the amastigotes of Leishmania amazonensis...
July 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Ana Díez-Izquierdo, Pia Cassanello-Peñarroya, Cristina Lidón-Moyano, Nuria Matilla-Santander, Albert Balaguer, Jose M Martínez-Sánchez
OBJECTIVE: The objective of this study is to perform a comprehensive review of the literature about thirdhand smoke (THS). METHODS: Systematic review of all aspects of THS. Standard methodological procedures were used to search the following databases through April 2018: MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science (WOS) in Indo-European languages. To identify published grey literature, the first 200 hits from Google Scholar™ were evaluated...
July 11, 2018: Environmental Research
Sofia Fortalezas, Dorinda Marques-da-Silva, Carlos Gutierrez-Merino
Rotenone is a neurotoxin that is an active component of many pesticides which has been shown to induce Parkinsonism in animal models. We show that the cytotoxicity of exposure to nanomolar concentrations of rotenone in cultures of mature cerebellar granule neurons (CGN) in serum-free medium is not due to phagocytosis by glial contamination. A concentration as low as 5.65 ± 0.51 nM of rotenone was enough to trigger 50% cell death of mature CGN in culture after 12 h. The addition of serum proteins to the culture medium attenuated rotenone neurotoxicity, and this can account at least in part for the requirement of higher rotenone concentrations to elicit neuronal cytotoxicity reported in previous works...
August 9, 2018: Neurotoxicity Research
Zhenzhen Huang, Kai He, Zhongxian Song, Guangming Zeng, Anwei Chen, Lei Yuan, Hui Li, Liang Hu, Zhi Guo, Guiqiu Chen
Antioxidative response of Phanerochaete chrysosporium induced by silver nanoparticles (AgNPs) and their toxicity mechanisms were comprehensively investigated in a complex system with 2,4-dichlorophenol (2,4-DCP) and Ag+ . Malondialdehyde content was elevated by 2,4-DCP, AgNPs, and/or Ag+ in concentration- and time-dependent manners within 24 h, indicating an increase in lipid peroxidation. However, beyond 48 h of exposure, lipid peroxidation was alleviated by upregulation of intracellular protein production and enhancement in the activities of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD)...
August 2, 2018: Chemosphere
Mariana Araki Braga, Kalina M Brauko, Maiara Vicentini, Lilian D Salgado, Helena C Silva de Assis, Rafael Garrett Dolatto, Marco T Grassi, Leonardo Sandrini-Neto, Paulo C Lana
Xenobiotics from oil tanker leaks and industrial discharges are amongst the main human impacts to confined coastal areas. We assessed the genotoxic responses to the water-soluble fraction of diesel oil in the polychaete Laeonereis culveri and the bivalve Anomalocardia flexuosa, two widespread benthic species in subtropical estuaries from the Southwestern Atlantic. We hypothesized that the highest responsiveness would be expressed by significantly different biomarkers responses between control and oil-impacted treatments...
August 6, 2018: Ecotoxicology and Environmental Safety
Prima Buranasin, Koji Mizutani, Kengo Iwasaki, Chantida Pawaputanon Na Mahasarakham, Daisuke Kido, Kohei Takeda, Yuichi Izumi
Delayed gingival wound healing is widely observed in periodontal patients with diabetes. However, the molecular mechanisms of the impaired function of gingival fibroblasts in diabetes remain unclear. The purpose of this study was to investigate changes in the properties of human gingival fibroblasts (HGFs) under high-glucose conditions. Primary HGFs were isolated from healthy gingiva and cultured with 5.5, 25, 50, and 75 mM glucose for 72 h. In vitro wound healing, 5-ethynyl-2'-deoxyuridine (EdU), and water-soluble tetrazolium salt (WST-8) assays were performed to examine cell migration and proliferation...
2018: PloS One
Tammy R Dugas, Gabrielle Brewer, Madison Longwell, Taylor Fradella, Jacob Braun, Carlos E Astete, Merilyn H Jennings, Cristina M Sabliov
Peripheral artery disease is a cardiovascular disease characterized by a narrowing of arteries that supply blood to the extremities, particularly, the legs. When surgical intervention is warranted, the primary approach is balloon angioplasty. Drug coated balloons (DCB) designed to release antimitogenic agents to the site of the blockage are a relatively new product aimed at reducing artery re-narrowing, or restenosis, after intervention. However, first generation DCB utilize mainly direct application of the chemotherapy drug paclitaxel, along with hydrophilic excipients to facilitate uptake into the tissue, and the majority of drug is released from the DCB systemically...
August 9, 2018: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
Suresh K Verma, Ealisha Jha, Pritam Kumar Panda, Mohana Mukherjee, Arun Thirumurugan, Hardik Makkar, Biswadeep Das, S K S Parashar, Mrutyunjay Suar
The toxicological impact of TiO2 nanoparticles on the environment and human health has been extensively studied in the last few decades, but the mechanistic details were unknown. In this study, we evaluated the impact of industrially prepared TiO2 nanoparticles on the biological system using zebrafish embryo as an in vivo model. The industrial synthesis of TiO2 nanoparticles was mimicked on the lab scale using the high energy ball milling (HEBM) method by milling bulk TiO2 particles for 5 h, 10 h, and 15 h in an ambient environment...
March 1, 2018: Toxicology Research
Lizeng Li, Si Chen, Yue Wang, Xia Yue, Jingtao Xu, Weibing Xie, Pingming Qiu, Chao Liu, AiFeng Wang, Huijun Wang
Methamphetamine (METH) is well-known as a potent psychostimulant of abuse worldwide. METH administration can cause neurotoxicity and neurodegenerative injury, which are similar to the two prevalent neurodegenerative disorders Alzheimer's disease (AD) and Parkinson's disease (PD). Recent results suggested that METH exposure increased the level of α-synuclein (α-syn) that could be a possible cause of neurotoxicity. However, the mechanism of METH-induced neurodegeneration remains unclear. This study was aimed at examining the effects of glycogen synthase kinase3β (GSK3β), α-syn, and tau on METH-induced neurotoxicity...
March 1, 2018: Toxicology Research
V Gies, S Zou
Understanding the toxicity of nanomaterials is essential for the safe and sustainable development of new applications. This is particularly true for a nanomaterial as widely used as graphene oxide (GO), which is utilized as films for electronics, membranes for filtration, drug carriers and more. Despite this, the current literature presents conflicting results on the overall toxicity of GO. Here, the cytotoxicity of three sizes of commercially available GO was investigated on six cell lines, as values of NOAEL/LOAEL...
January 1, 2018: Toxicology Research
Anita R Iskandar, Yannick Martinez, Florian Martin, Walter K Schlage, Patrice Leroy, Alain Sewer, Laura Ortega Torres, Shoaib Majeed, Celine Merg, Keyur Trivedi, Emmanuel Guedj, Stefan Frentzel, Carole Mathis, Nikolai V Ivanov, Manuel C Peitsch, Julia Hoeng
Using an in vitro human small airway epithelium model, we assessed the biological impact of an aerosol from a candidate modified-risk tobacco product, the tobacco heating system (THS) 2.2, to investigate the potential reduced risk of THS2.2 aerosol exposure compared with cigarette smoke. Following the recommendations of the Institute of Medicine and the Tobacco Product Assessment Consortium, in which modified-risk tobacco products assessment should be performed in comparison with standard conventional products, the effects of the THS2...
November 1, 2017: Toxicology Research
Norio Kamemura, Keisuke Oyama, Kaori Kanemaru, Kumio Yokoigawa, Yasuo Oyama
Tertiary butylhydroquinone (TBHQ) is a food additive that possesses antioxidant activity. Its alternative applications have been explored in recent studies. However, there is controversy regarding safety. In this study using rat thymocytes, the cellular actions of TBHQ at sublethal concentrations were examined. TBHQ at concentrations of 3 μM or more elevated intracellular Zn2+ concentration ([Zn2+ ]i ) in a dose-dependent manner, by increasing membrane Zn2+ permeability and releasing Zn2+ from cellular stores...
November 1, 2017: Toxicology Research
Farshad Homayouni Moghadam, Mehrnaz Mesbah-Ardakani, Mohammad Hossein Nasr-Esfahani
Objectives: Based on data from Chinese and Indian traditional herbal medicines, gum resin of Ferula assa-foetida (sometimes referred to asafetida or asafoetida) has several therapeutic applications. The authors of various studies have claimed that asafetida has cytotoxic, antiulcer, anti-neoplasm, anti-cancer, and anti-oxidative effects. In present study, the anti-aging effect of asafetida on senescent human dermal fibroblasts was evaluated. Methods: Senescence was induced in in vitro cultured human dermal fibroblasts (HDFs) through exposure to H2 O2 , and the incidence of senescence was recognized by using cytochemical staining for the activity of β -galactosidase...
September 2017: Journal of Pharmacopuncture
Hamed Karkehabadi, Hosnieh Yousefifakhr, Saeede Zadsirjan
Introduction: Root canal irrigation has an extremely important role in the success of endodontic treatment. During endodontic treatment, the irrigants will be in contact with pulpal and periapical tissues. The purpose of this study was to clarify the potential toxicological implications of NaOCl, EDTA, MTAD, CHX and QMix on periapical and periodontal tissues. Methods and Materials: Cytotoxicity of solutions was evaluated on cultured human periodontal ligament (hPDL) that were carefully removed from the middle third of premolar roots...
2018: Iranian Endodontic Journal
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