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Journal of Applied Toxicology: JAT

Gabriela Guerrero-Palomo, Erika P Rendón-Huerta, Luis F Montaño, Teresa I Fortoul
Non-small lung cell carcinoma has a high morbidity and mortality rates. The elective treatment for stage III and IV is cisplatinum that conveys serious toxic side effects. Vanadium compounds are metal molecules with proven antitumor activity that depends on its valence. Therefore, a better understanding of the mechanism of action of vanadium compounds is required. The aim of our study was to investigate the mechanisms of cell death induced by sodium metavanadate (NaVO3 [V(+5)]) and vanadyl sulfate (VOSO4 [(+4)]), both of which have reported apoptotic-inducing activity...
November 8, 2018: Journal of Applied Toxicology: JAT
Juyoung K Shim, Rachel H Kennedy, Lisa M Weatherly, Andrew V Abovian, Hina N Hashmi, Atefeh Rajaei, Julie A Gosse
Mast cells comprise a physiologically and toxicologically important cell type that is ubiquitous among species and tissues. Mast cells undergo degranulation, in which characteristic intracellular granules fuse with the plasma membrane and release many bioactive substances, such as enzymes β-hexosaminidase and tryptase. Activity of mast cells in the toxicology model organism, zebrafish, has been monitored via tryptase release and cleavage of substrate N-α-benzoyl-dl-Arg-p-nitroanilide (BAPNA). An extensively used in vitro mast cell model for studying toxicant mechanisms is the RBL-2H3 cell line...
October 30, 2018: Journal of Applied Toxicology: JAT
Jun Zhang, Yan Wang, Lin Fu, Bo Wang, Yan-Li Ji, Hua Wang, De-Xiang Xu
Previous studies have revealed that acute cadmium (Cd) exposure led to inflammation in different organs through an oxidative stress mechanism. However, whether chronic Cd exposure induces inflammation in liver and the mechanistic link between inflammation and cell stress remains unclear. In the present study, we investigated the effects of chronic Cd exposure on hepatic cellular stress and inflammatory responses. Female CD1 mice were administrated with CdCl2 (10 and 100 mg/L) in drinking water for 57 weeks...
October 29, 2018: Journal of Applied Toxicology: JAT
Nidal A Qinna, Bayan Y Ghanim
The urge of identifying new pharmacological interventions to prevent or attenuate liver injury is of critical importance and needs an expanded experimental toolbox. Hepatocyte injury and cellular death is a prominent feature behind the pathology of liver diseases. Several research activities focused on identifying chemicals and hepatotoxicants that induce cell death by apoptosis, in addition to presenting its corresponding signaling pathway. Although such efforts provided further understanding of the mechanisms of cell death, it has also raised confusion concerning identifying the involvement of several modes of cell death including apoptosis, necrosis and fibrosis...
October 23, 2018: Journal of Applied Toxicology: JAT
Pål A Olsvik, Marte Aulin, Ole B Samuelsen, Rita Hannisdal, Ann-Lisbeth Agnalt, Bjørn T Lunestad
The benzoylurea chitin synthesis inhibitor teflubenzuron, widely used against sea lice in North Atlantic aquaculture, may pose an environmental threat to non-targeted crustaceans. In this experiment, laboratory acclimated pink shrimp (Pandalus montagui), a species found in fjords with Atlantic salmon farming, were exposed to dietary teflubenzuron for 46 days (control; low dose: 0.01 μg/g; high dose: 0.1 μg/g). The exposure doses represent 0.1% and 1% of a standard treatment dose for Atlantic salmon. Mortality and prevalence of deformities, pharmacokinetics, oxidative stress and transcriptomic and metabolomic profiling were used to assess the response to teflubenzuron exposure...
October 21, 2018: Journal of Applied Toxicology: JAT
C Géniès, E L Jamin, L Debrauwer, D Zalko, E N Person, J Eilstein, S Grégoire, A Schepky, D Lange, C Ellison, A Roe, S Salhi, R Cubberley, N J Hewitt, H Rothe, M Klaric, H Duplan, C Jacques-Jamin
Skin metabolism is important to consider when assessing local toxicity and/or penetration of chemicals and their metabolites. If human skin supply is limited, pig skin can be used as an alternative. To identify any species differences, we have investigated the metabolism of 10 chemicals in a pig and human skin explant model. Phase I metabolic pathways in skin from both species included those known to occur via cytochrome P450s, esterases, alcohol dehydrogenases and aldehyde dehydrogenases. Common Phase II pathways were glucuronidation and sulfation but other conjugation pathways were also identified...
October 21, 2018: Journal of Applied Toxicology: JAT
Sho Akai, Shingo Oda, Tsuyoshi Yokoi
Lamotrigine (LTG) has been widely prescribed as an antipsychotic drug, although it causes idiosyncratic drug-induced liver injury in humans. LTG is mainly metabolized by UDP-glucuronosyltransferase, while LTG undergoes bioactivation by cytochrome P450 to a reactive metabolite; it is subsequently conjugated with glutathione, suggesting that reactive metabolite would be one of the causes for LTG-induced liver injury. However, there is little information regarding the mechanism of LTG-induced liver injury in both humans and rodents...
October 16, 2018: Journal of Applied Toxicology: JAT
Meiyan Zhang, Siqi Jia, Yajing Liu, Yanli Liu, Siqi Li, Lu Bo, Xiujuan Zhao, Changhao Sun
This study aimed to investigate the nephrotoxicity in rats administered with chronic low-dose cadmium (Cd) by ultra-performance liquid chromatography-mass spectrometry. A total of 40 male Sprague-Dawley rats were randomly assigned to four groups, namely: control; low-dose (0.13 mg/kg·body weight [bw]); middle-dose (0.80 mg/kg·bw); and high-dose (4.89 mg/kg·bw). The rats received CdCl2 daily via drinking water for 24 weeks. Rat kidneys were collected for metabonomics analysis. Principal components analysis and partial least-squares discriminant analysis were used to investigate the metabonomics profile changes in the kidney samples and to screen the potential biomarkers...
October 16, 2018: Journal of Applied Toxicology: JAT
Cristina Avonto, Yan-Hong Wang, Amar G Chittiboyina, Stanislav Vukmanovic, Ikhlas A Khan
Twenty-four pure fragrance ingredients of concern as potential skin sensitizers were previously subjected to degradation studies and evaluated using the high throughput with dansyl cysteamine (HTS-DCYA) method. The experimental results showed that two-thirds of the 24 fragrance ingredients underwent chemical degradation. In some cases, such degradation was accompanied by an increase in thio-reactivity. These results prompted us to investigate the reactivity of the same ingredients using the direct peptide reactivity assay (DPRA)...
October 16, 2018: Journal of Applied Toxicology: JAT
Felix Hammann, Verena Schöning, Jürgen Drewe
Drug-induced liver injury (DILI) is the most common cause of acute liver failure and often responsible for drug withdrawals from the market. Clinical manifestations vary, and toxicity may or may not appear dose-dependent. We present several machine-learning models (decision tree induction, k-nearest neighbor, support vector machines, artificial neural networks) for the prediction of clinically relevant DILI based solely on drug structure, with data taken from published DILI cases. Our models achieved corrected classification rates of up to 89%...
October 16, 2018: Journal of Applied Toxicology: JAT
Carrie L German, Sundararajan V Madihally
Recent advances in developing in vitro tissue models show that function of hepatocytes is altered in when cultured in 3D configuration and co-culturing with various non-parenchymal cells. However, tissue source for such non-parenchymal cells on viability and metabolic products of hepatocytes have not been explored. In this study, we evaluated the effect of 2D and 3D cultures either with HepaRG cells alone or in combination with liver sinusoidal endothelial cells (LSECs) and human umbilical vein ECs (HUVECs)...
October 11, 2018: Journal of Applied Toxicology: JAT
Shilpi Singh, Shio Kumar Singh
Perfluoroalkyl acids (PFAAs) are widely used in commercial applications and that they are ubiquitous and persistent in the environment. Perfluorononanoic acid (PFNA), a member of PFAAs, has been detected in human and wildlife. Previous acute exposure studies have shown the adverse effect of PFNA on the testis. The present study was aimed to examine the effect of chronic PFNA exposure, from prepuberty to adulthood, on testicular functions and fertility in Parkes (P) male mice and to investigate the possible mechanism(s) of its action...
October 7, 2018: Journal of Applied Toxicology: JAT
Amir Shadboorestan, Ghorban Ali Tarfiei, Hamed Montazeri, Mohammad Reza Sepand, Mohammad Zangooei, Azam Khedri, Seyed Nasser Ostad, Mohammad Hossein Ghahremani
Benzo[α]pyrene (BaP) can have significant role in the development of breast cancer via aryl hydrocarbon receptor (AhR) activation. AhR activation has been studied in several functions such as survival, migration and invasion of cancer cells. In cancer, integrins contribute to the migration/invasion process and are regulated by nuclear factor of activated T cells (NFAT) and transforming growth factor (TGF) beta pathways. The aim of the present study was to examine the effect of BaP, an activator of AhR and cyclosporine A (CsA), as inhibitor of NFAT on migration and invasion of MDA-MB-231 cells...
October 7, 2018: Journal of Applied Toxicology: JAT
Yuan Song, Takamichi Ichinose, Kentaro Morita, Yasuhiro Yoshida
Asian sand dust (ASD), a type of particulate matter (PM) found in Asia, can be transported to East Asia. We recently found that acute splenic inflammation is induced by ASD in mouse models. In this study, we examined the effect of sub-chronic ASD exposure on mouse immune cells. Mice were intratracheally administered ASD once every 2 weeks for 8 weeks and killed 24 hours after the final administration. Wild-type (WT) mice showed increased cell viability after ASD administration. In contrast, ASD administration induced splenocyte activation in toll-like receptor (TLR)2-/- , but not TLR4-/- mice...
October 5, 2018: Journal of Applied Toxicology: JAT
Wei Zhou, Dongdong Tian, Jun He, Xiabei Yan, Jun Zhao, Xiaoyan Yuan, Shuangqing Peng
Growing black carbon (BC) emission has become one of the major urgent environmental issues facing human beings. Usually, BC or BC-containing carbon nanoparticles (CNPs) were recognized as non-directly toxic components of atmospheric particulate matter. However, epidemiology studies have provided much evidence of the associations of exposure of particulate-containing carbon particles with cardiovascular diseases. There are still no related studies to support the epidemiological conclusions. Hence, in this article we exposed adult zebrafish to CNPs for 60 days, and then explored the heart location and potential adverse effects on cardiac tissues of these nanosized carbon particles...
October 5, 2018: Journal of Applied Toxicology: JAT
You-Wei Bai, Meng-Juan Ye, Da-Long Yang, Meng-Ping Yu, Cheng-Fan Zhou, Tong Shen
Exogenous H2 S donor, sodium hydrosulfide (NaHS), can influence the bleomycin-induced pulmonary fibrosis by attenuating the epithelial-mesenchymal transition (EMT) of alveolar epithelial cells, but whether NaHS affects paraquat (PQ)-induced EMT and the molecular mechanisms remain unclarified. The aim of the present study is to examine the effect of exogenous NaHS on PQ-induced EMT in human alveolar epithelial cells (A549 cells) and assess if this effect occurs through regulating transforming growth factor (TGF)-β1/Smad2/3 signaling pathway...
September 28, 2018: Journal of Applied Toxicology: JAT
So-Ryeon Hwang, Nga Thi Thu Tham, Soo-Ho Lee, Ji-Hyun Bang, Hee Yi, Young-Il Park, Hyun-Kyoung Lee, Hwan-Goo Kang, Yong-Sang Kim, Gye-Hyeong Woo, Hyun-Ok Ku
Biofluid-based biomarkers provide an efficient tool for hazard identification of chemicals. Here, we explored the potential of microRNAs (miRNAs) as biomarkers for hepatotoxicity of chemicals by linking in vitro to in vivo animal models. A search of the literature identified candidate circulating miRNA biomarkers of chemical-induced hepatotoxicity. The expression of candidate miRNAs (miR-122, miR-151a, miR-192, miR-193a, miR-194, miR-21, miR-29c), was determined by real-time reverse transcription-polymerase chain reaction in in vivo acute liver injury induced by acetaminophen, and then were further compared with those of in vitro cell assays...
September 28, 2018: Journal of Applied Toxicology: JAT
Xialu Lin, Wanzhen Shao, Fangfang Yu, Ke Xing, Huan Liu, Feng'e Zhang, Mary B Goldring, Mikko J Lammi, Xiong Guo
Deoxynivalenol (DON) and T-2 toxin are prevalent mycotoxin contaminants in the food and feed stuffs worldwide, with non-negligible co-contamination and co-exposure conditions. Meanwhile, they are considerable risk factors for Kashin-Beck disease, a chronic endemic osteochondropathy. The aim of this study was to investigate the individual and combined cytotoxicity of DON and T-2 toxin on proliferating human C-28/I2 and newborn rat primary costal chondrocytes by MTT assay. Four molar concentration combination ratios of DON and T-2 toxin were used, 1:1 for R1 mixture, 10:1 for R10, 100:1 for R100 and 1000:1 for R1000...
September 25, 2018: Journal of Applied Toxicology: JAT
Hufei Wang, Jiamin Chen, Megumi Suda, Yukie Yanagiba, Zuquan Weng, Rui-Sheng Wang
1,2-Dichloropropane (1,2-DCP) is used as an industrial solvent, insecticide fumigant and household dry cleaning product. Carcinogenicity caused by long-term exposure to 1,2-DCP is well established. However, the possible liver damage and related toxic mechanisms associated with acute inhalation exposure to 1,2-DCP are rarely reported. In this study, we investigated the effects of individual and combined exposure to 1,2-DCP and dichloromethane (DCM) on mice liver. The results showed that 1,2-DCP significantly caused liver necrosis, possibly due to 1,2-DCP-induced inhibition of the mitochondrial respiratory chain complex I-IV activities, resulting in mitochondrial dysfunction and extreme ATP consumption...
September 21, 2018: Journal of Applied Toxicology: JAT
Gabriel Adan Araujo Leite, Jorge Willian Franco de Barros, Airton da Cunha Martins, Janete Aparecida Anselmo-Franci, Fernando Barbosa, Wilma De Grava Kempinas
Dyslipidemias are occurring earlier in the population due to the augmentation of obesity. Rosuvastatin reduces cholesterol and triglycerides; however, previous studies have shown that it may affect male reproduction. Ascorbic acid (AA), an antioxidant compound, plays a protective role in the male reproductive system. This study aimed to evaluate whether pre-pubertal exposure to rosuvastatin may impair testicular structure and antioxidant status in male rats and if supplementation with AA may alleviate these damages...
September 21, 2018: Journal of Applied Toxicology: JAT
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