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Journal of Applied Toxicology: JAT

Zhangjian Chen, Di Zhou, Shupei Zhou, Guang Jia
Existing literature pointed out that the liver may be the target organ of toxicity induced by titanium dioxide nanoparticles (TiO2 NPs) via oral exposure. Gender differences in health effects widely exist and relevant toxicological research is important for safety assessment. To explore the gender susceptibility of TiO2 NP-induced hepatic toxicity and the underlying mechanism, we examined female and male Sprague-Dawley rats administrated with TiO2 NPs orally at doses of 0, 2, 10 and 50 mg/kg body weight per day for 90 days...
January 15, 2019: Journal of Applied Toxicology: JAT
Jiamao Chen, Ting Yang, Jimin Long, Yanhuai Ding, Juan Li, Xianqiang Li, Yi Cao
We recently synthesized ZnO nanomaterials (denoted as ZnO nanorods [NRs] and Mini-NRs) and suggested that their cytotoxicity could be related with the activation of endoplasmic reticulum (ER) stress apoptosis. However, in a complex biological microenvironment, the ER stress-apoptosis pathway could also be modulated by biological molecules, such as free fatty acids, leading to unpredicted biological effects. In this study, we investigated the combined toxicity of ZnO NRs/Mini-NRs and palmitate (PA) to THP-1 macrophages...
January 8, 2019: Journal of Applied Toxicology: JAT
Evan M Beckett, William D Cyrs, Anders Abelmann, Andrew D Monnot, Shannon H Gaffney, Brent L Finley
Occupational exposure limits (OELs) have been previously proposed for diacetyl; however, most of these values are based on worker cohort studies that are known to have several limitations and confounders. In this analysis, an 8 hour time-weighted average (TWA) OEL for diacetyl was derived based on data from a chronic, 2 year animal inhalation study recently released by the US National Toxicology Program. In that study, complete histopathology was conducted on male and female mice and rats exposed to 0, 12...
January 8, 2019: Journal of Applied Toxicology: JAT
Lakshmi Sai Pratyusha Bugata, Prabhakar Pitta Venkata, Ananth Reddy Gundu, Rahman Mohammed Fazlur, Utkarsh A Reddy, Jerald Mahesh Kumar, Venugopala Reddy Mekala, Sreedhar Bojja, Mohammed Mahboob
The extensive use of copper oxide nanoparticles (CuO-NPs) in various industries and their wide range of applications have led to their accumulation in different ecological niches of the environment. This excess exposure raises the concern about its potential toxic effects on various organisms including humans. However, the hazardous potential of CuO-NPs in the literature is elusive, and it is essential to study its toxicity in different biological models. Hence, we have conducted single acute dose (2000 mg/kg) and multiple dose subacute (30, 300 and 1000 mg/kg daily for 28 days) oral toxicity studies of CuO-NPs in female albino Wistar rats following OECD guidelines 420 and 407 respectively...
January 7, 2019: Journal of Applied Toxicology: JAT
Abhishek Kumar Jain, Divya Singh, Kavita Dubey, Renuka Maurya, Alok Kumar Pandey
In recent years, the large-scale production of ZnO nanoparticles (NPs) for various applications is increasing exponentially and may pose serious health issues when inhaled either during occupational exposure or in consumer settings. The mechanisms underlying the toxicity of NPs have recently been studied intensively. Despite the existing studies, the mutagenicity of ZnO NPs in the eukaryotic system is still unclear. Therefore, the aim of the present study was to investigate the mutagenic potential of ZnO NPs using Chinese hamster lung fibroblast cells (V-79) as an in-vitro model...
January 7, 2019: Journal of Applied Toxicology: JAT
Sara Nahle, Ramia Safar, Stéphanie Grandemange, Bernard Foliguet, Mélanie Lovera-Leroux, Zahra Doumandji, Alain Le Faou, Olivier Joubert, Bertrand Rihn, Luc Ferrari
Human exposure to airborne carbon nanotubes (CNT) is increasing because of their applications in different sectors; therefore, they constitute a biological hazard. Consequently, developing studies on CNT toxicity become a necessity. CNTs can have different properties in term of length, size and charge. Here, we compared the cellular effect of multiwall (MWCNTs) and single wall CNTs (SWCNTs). MWCNTs consist of multiple layers of graphene, while SWCNTs are monolayers. The effects of MWCNTs and SWCNTs were evaluated by the water-soluble tetrazolium salt cell proliferation assay on NR8383 cells, rat alveolar macrophage cell line (NR8383)...
January 3, 2019: Journal of Applied Toxicology: JAT
Jitka Vostálová, Adéla Galandáková, Bohumil Zálešák, Radka Lichnovská, Kateřina Čížková, Jitka Ulrichová, Alena Rajnochová Svobodová
Human skin explant (HSE) seems to be a useful model for dermatological/cosmetic testing. HSE prepared from donor superfluous skin from plastic surgery operations is cheap and easily obtainable compared to reconstructed models. The HSE use, however, may be limited by the degeneration processes during cultivation. The aim was to monitor changes in metabolic activity and selected apoptotic, inflammatory and antioxidant parameters during 7 day cultivation. The significant changes were found in the superoxide dismutase-2 level from day 5, glutathione S-reductase level from day 6, metabolic activity and fibulin-5 level from day 4, cyclooxygenase-2, interleukin-6 and interleukin-10 from day 1 to 2...
January 3, 2019: Journal of Applied Toxicology: JAT
Haoyu Huang, Ran Jiang, Zhenwei Lian, Wenjuan Zhang, Zuqing Hu, Dalin Hu
Temozolomide (TMZ), a therapeutic DNA alkylator that can cause lethal DNA damage in cancer cells, is widely used for the standard chemotherapy against glioblastoma. However, long-term treatment with TMZ often causes drug resistance and poor prognosis, the mechanism of which remains largely unclear. This study aimed to investigate the possible role of miR-222/GAS5 axis on DNA damage and cytotoxic effects induced by TMZ in glioblastoma cells (T98G). Data suggest that the DNA comet tail length of T98G is positively correlated with the levels of miR-222 (R2  = 0...
December 21, 2018: Journal of Applied Toxicology: JAT
Takashi Sekine, Tadashi Hirata, Shinkichi Ishikawa, Shigeaki Ito, Kanae Ishimori, Kazushi Matsumura, Katsuhiko Muraki
Cigarette smoke (CS) is a complex mixture of chemicals and interacts with various physiological processes. We previously reported that nuclear factor erythroid 2-related factor 2 (NRF2) was the most sensitive transcription factor to aqueous CS extract (AqCSE) exposure in monolayer cultured human bronchial epithelial cell lines. Recently, in vitro three-dimensional (3D) culture models have been used to supplement pharmacological and toxicological assessments. Bronchial epithelium models in particular are useful for the evaluation of substances that directly contact the respiratory tract, such as CS...
December 21, 2018: Journal of Applied Toxicology: JAT
Kosuke Saito, Nozomi Tanaka, Jun Ikari, Masaki Suzuki, Rie Anazawa, Mitsuhiro Abe, Yoshiro Saito, Koichiro Tatsumi
Drug-induced lung injury is an adverse effect of drug treatment that can result in respiratory failure. Because lipid profiling could provide cutting-edge understanding of the pathophysiology of toxicological responses, we performed lipidomic analyses of drug-induced lung injury. We used a mouse model of bleomycin-induced lung injury and followed the physiological responses at the acute inflammatory (day 2), inflammatory-to-fibrosis (day 7) and fibrosis (day 21) phases. The overall lipid profiles of plasma, lung and bronchoalveolar lavage fluid (BALF) revealed that drastic changes in lipids occurred in the lung and BALF, but not in the plasma, after 7 and 21 days of bleomycin treatment...
December 18, 2018: Journal of Applied Toxicology: JAT
Gokulapriya Rajagopal, Ravi Sankar Bhaskaran, Balasubramanian Karundevi
Di-(2-ethylhexyl) phthalate (DEHP) is a commonly used plasticizer with endocrine disrupting properties. Its widespread use resulted in constant human exposure including fetal development and postnatal life. Epidemiological and experimental data have shown that DEHP has a negative influence on glucose homeostasis. However, the evidence regarding the effect of maternal DEHP exposure on hepatic glucose homeostasis is scarce. Hence, we investigated whether DEHP exposure during gestation and lactation disrupts glucose homeostasis in the rat F1 male offspring at adulthood...
December 18, 2018: Journal of Applied Toxicology: JAT
Jillian R Hufgard, Jenna L N Sprowles, Emily M Pitzer, Sheryl E Koch, Min Jiang, Qin Wang, Xiang Zhang, Jacek Biesiada, Jack Rubinstein, Alvaro Puga, Michael T Williams, Charles V Vorhees
Polychlorinated biphenyls (PCBs) are toxic environmental pollutants. Humans are exposed to PCB mixtures via contaminated food or water. PCB exposure causes adverse effects in adults and after exposure in utero. PCB toxicity depends on the congener mixture and CYP1A2 gene activity. For coplanar PCBs, toxicity depends on ligand affinity for the aryl hydrocarbon receptor (AHR). Previously, we found that perinatal exposure of mice to a three-coplanar/five-noncoplanar PCB mixture induced deficits in novel object recognition and trial failures in the Morris water maze in Cyp1a2-/- ::Ahrb1 C57BL6/J mice compared with wild-type mice (Ahrb1  = high AHR affinity)...
December 18, 2018: Journal of Applied Toxicology: JAT
Kaori Sadakane, Takamichi Ichinose, Masataka Nishikawa
During the 2000s, Asian sand dust (ASD) was implicated in the increasing prevalence of respiratory disorders, including asthma. We previously demonstrated that a fungus from ASD aerosol exacerbated ovalbumin (OVA)-induced airways inflammation. Exposure to heat-inactivated ASD (H-ASD) and either Zymosan A (ZymA, containing β-glucan) or lipopolysaccharide (LPS) exacerbated allergic airways inflammation in a mouse model, but the effects of co-exposure of LPS and β-glucan are unclear. We investigated the effects of co-exposure of LPS and ZymA in OVA-induced allergic airways inflammation with ASD using BALB/c mice...
December 12, 2018: Journal of Applied Toxicology: JAT
Keyu He, Xue Liang, Tingting Wei, Na Liu, Yan Wang, Linyue Zou, Jie Lu, Ying Yao, Lu Kong, Ting Zhang, Yuying Xue, Tianshu Wu, Meng Tang
Microglial cells are resident immune cells in the central nervous system. Activation of microglia as induced by CdTe quantum dots (QDs) can trigger damage to neurons. To quantify the intracellular QDs, we monitored the intracellular Cd concentration in the QD-exposed mouse microglial cells (BV-2 cell line). The extent of cell injury at different times correlated with the Cd concentration in cells at that time. In addition to Cd ion detection, we also monitored the intracellular fluorescence of the QDs. More QDs accumulated in the nucleus than in the cytoplasm...
December 4, 2018: Journal of Applied Toxicology: JAT
Isabel Pereira, Sónia Fraga, Susana Silva, João Paulo Teixeira, Miguel Gama
Hydrogels are three-dimensional, crosslinked networks of hydrophilic polymers swollen with a large amount of water or biological fluids, without dissolving. Dextrin, a low-molecular-weight carbohydrate composed by glucose residues, has been used to develop an injectable hydrogel for biomedical applications. Dextrin was first oxidized to introduce aldehyde groups, which then reticulate with adipic acid dihydrazide, forming the dextrin-based hydrogel (HG). The HG and its components were tested for cyto- and genotoxicity according to the International Standard ISO 10993-3 on the biological evaluation of medical devices...
November 28, 2018: Journal of Applied Toxicology: JAT
Eun-Jung Park, Yoo-Jin Park, Sang Jin Lee, Cheolho Yoon, Kyuhong Lee
Cigarette smoke is known to be associated with the incidence of a variety of pulmonary diseases, and alveolar macrophages are a key player in the defense mechanism against inhalable toxicants. Herein, we have found that a hydrophilic fraction in smoke extracts from 3R4F reference cigarettes (CSE) contains high concentrations of volatile substances compared to cigarette smoke condensate (amphoteric fraction). We also identified the toxic mechanism of CSE using MH-S, a mouse alveolar macrophage cell line. CSE decreased cell viability accompanying increased lactate dehydrogenase release...
November 28, 2018: Journal of Applied Toxicology: JAT
Jorge Muñoz-Sánchez, María E Chánez-Cárdenas
The use of hypoxia models in cell culture has allowed the characterization of the hypoxia response at the cellular, biochemical and molecular levels. Although a decrease in oxygen concentration is the optimal hypoxia model, the problem faced by many researchers is access to a hypoxia chamber or a CO2 incubator with regulated oxygen levels, which is not possible in many laboratories. Several alternative models have been used to mimic hypoxia. One of the most commonly used models is cobalt chloride-induced chemical hypoxia because it stabilizes hypoxia inducible factors 1α and 2α under normoxic conditions...
November 28, 2018: Journal of Applied Toxicology: JAT
Yoshifumi Horie, Takahiro Yamagishi, Ayano Yagi, Yoko Shintaku, Taisen Iguchi, Norihisa Tatarazako
Diclofenac sodium, a non-steroidal anti-inflammatory drug widely used in both human and veterinary medicine, has been detected in aquatic environments; therefore, its ecotoxicological effects on aquatic organisms need to be clarified. Recently, toxicity testing using zebrafish (Danio rerio) embryos has been recommended from the point of view of animal welfare; therefore, we investigated the suitability of using sub-lethal endpoints observed during embryogenesis for predicting lethal effects in early life stage zebrafish exposed to diclofenac sodium...
November 20, 2018: Journal of Applied Toxicology: JAT
Andréa P Carnizello, Jacqueline M Alves, Daiane E Pereira, Jacqueline C L Campos, Marília I F Barbosa, Alzir A Batista, Denise C Tavares
Considering the promising previous results of ct-[RuCl(CO)(dppb)(bipy)]PF6 (where dppb = 1,4-bis(diphenylphosphino)butane and bipy = 2,2'-bipyridine) as an antitumor agent, novel biological assays evaluating its toxicogenic potential were performed. The genotoxicity of the compound was evaluated by the in vitro micronucleus test (V79, Chinese hamster lung fibroblasts; HepG2, hepatocellular carcinoma cells), in vivo bone marrow micronucleus test and comet assay in hepatocytes (Swiss mice). The animals were treated with 0...
November 20, 2018: Journal of Applied Toxicology: JAT
Zhangjian Chen, Di Zhou, Yun Wang, Lin Zhao, Guiping Hu, Jiaxing Liu, Huimin Feng, Changmao Long, Tenglong Yan, Shupei Zhou, Guang Jia
Titanium dioxide nanoparticles (TiO2 NPs) have already been used as food additive in various products and are usually consumed with a considerable amount of sugar. Oral consumption of TiO2 NPs poses concerning health risks; however, research on the combined effect of ingested TiO2 NPs and glucose is limited. We examined young Sprague-Dawley rats administrated TiO2 NPs orally at doses of 0, 2, 10 and 50 mg/kg body weight per day with and without 1.8 g/kg body weight glucose for 30 and 90 days. Heart rate, systolic and diastolic blood pressure, blood biochemical parameters and histopathology of cardiac tissues was assessed to quantify cardiovascular damage...
November 14, 2018: Journal of Applied Toxicology: JAT
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