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Journal of Applied Toxicology: JAT

Shanieek Lawrence, Farah Ismail, Sarah Z Jamal, Margaret M Whalen
Tributyltin (TBT) is found in human blood and other tissues and thus is of considerable concern as to its effects on human health. Previous studies have demonstrated that TBT has detrimental effects on immune function. Recently, we found that exposures to TBT caused increased secretion of two important proinflammatory cytokines, tumor necrosis factor alpha (TNFα) and interferon gamma (IFNγ). Elevation of either of these cytokines has the potential to cause chronic inflammation, which is an important factor in a number of diseases including cancer...
March 13, 2018: Journal of Applied Toxicology: JAT
Jing Song, Masaki Nagae, Kiyoshi Soyano
Field surveys of the impact of environmental estrogen (EE) pollution in aquatic wildlife have been conducted using vitellogenin (VTG) as a biomarker to evaluate the influence of EE. However, a standard baseline of VTG level that can be used to evaluate EE pollution has not been fully determined. To the best of our knowledge, the present study is the first to determine the standard baseline VTG level for evaluating the biological effects of EE pollution using the Japanese common goby (Acanthogobius flavimanus) as the target model fish...
March 9, 2018: Journal of Applied Toxicology: JAT
Nela Vanova, Jaroslav Pejchal, David Herman, Alzbeta Dlabkova, Daniel Jun
Despite the main mechanism of organophosphate (OP) toxicity through inhibition of acetylcholinesterase (AChE) being well known over the years, some chronic adverse health effects indicate the involvement of additional pathways. Oxidative stress is among the most intensively studied. Overstimulation of cholinergic and glutamatergic nervous system is followed by intensified generation of reactive species and oxidative damage in many tissues. In this review, the role of oxidative stress in pathophysiology of OP poisoning and the influence of commonly used medical interventions on its levels are discussed...
March 8, 2018: Journal of Applied Toxicology: JAT
Kwang Sik Suh, Eun Mi Choi, Hyun-Sook Kim, So Young Park, Sang Ouk Chin, Sang Youl Rhee, Youngmi Kim Pak, Wonchae Choe, Joohun Ha, Suk Chon
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant. Xanthohumol is a prenylated flavonoid found in hops (Humulus lupulus) and beer. The aim of the current study was to explore the role of xanthohumol in modulating the toxicity of TCDD in MC3T3-E1 osteoblastic cells. In cells treated with TCDD alone, intracellular Ca2+ concentrations, mitochondrial membrane potential disruption, reactive oxygen species production, cardiolipin peroxidation, nitric oxide release and cytochrome P450 1A1 expression were significantly increased...
March 8, 2018: Journal of Applied Toxicology: JAT
Byung-Woo Lee, Byung-Suk Jeon, Byung-Il Yoon
Thioredoxin-1 (Trx-1) is a potent therapeutic agent against a variety of diseases because of its actions as an antioxidant and regulator of apoptosis. N-acetyl-p-aminophenol (APAP), commonly known as acetaminophen, generates excessive oxidative stress and triggers hepatocyte cell death, exemplified by regulated necrosis. In the present study, we investigated whether APAP-induced liver injury in a mouse model is associated with "necroptosis," and if pretreatment with recombinant Trx-1 prevents the hepatic injury caused by APAP overdose...
March 7, 2018: Journal of Applied Toxicology: JAT
Edyta Andrulewicz-Botulińska, Róża Wiśniewska, Malgorzata M Brzóska, Joanna Rogalska, Anna Galicka
Cadmium (Cd) is a toxic metal that damages bone tissue by affecting its mineral and organic components. The organic matrix is mainly (90%) composed of collagen, which determines the biomechanical strength of bone. The aim of this study was to evaluate the effect of zinc (Zn) supplementation (30 or 60 mg l-1 ) under moderate and relatively high exposure to Cd (5 and 50 mg l-1 ) on collagen in the rat tibia proximal epiphysis and diaphysis (regions abundant in trabecular and cortical bone, respectively). Significant decrease in collagen type I biosynthesis was found in both regions of the tibia in Cd-treated rats, whereas the supplementation with Zn provided significant protection against this effect...
March 5, 2018: Journal of Applied Toxicology: JAT
Shuzhen Chen, Suyun Chen, Yun Zeng, Lin Lin, Chuang Wu, Yanyan Ke, Gang Liu
Superparamagnetic iron oxide nanoparticles (SPIONs) have been widely investigated for their biomedical applications in magnetic resonance imaging, targeting therapy, cell labeling, etc. It has been well documented that macrophages produce interleukin (IL)-1β via several signaling pathways, such as inflammasome activation in response to particles including silica, asbestos and urea crystals with lipopolysaccharide priming. However, the size and dose effects of SPIONs on macrophages and the mechanisms remain unclear...
February 28, 2018: Journal of Applied Toxicology: JAT
Xi Yang, Thomas Papoian
Drug-induced cardiotoxicity is a potentially severe side effect that can adversely affect myocardial contractility through structural or electrophysiological changes in cardiomyocytes. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a promising human cardiac in vitro model system to assess both proarrhythmic and non-proarrhythmic cardiotoxicity of new drug candidates. The scalable differentiation of hiPSCs into cardiomyocytes provides a renewable cell source that overcomes species differences present in current animal models of drug toxicity testing...
February 27, 2018: Journal of Applied Toxicology: JAT
Weijia Gu, Yi Wang, Zhenmin Qiu, Jing Dong, Yuan Wang, Jie Chen
Microglia (MG) are the key cells involved in the innate immune response in the central nervous system, and their activation has been linked to inflammation and neurotoxicity by the production of proinflammatory cytokines. Recently, researchers have found that nonylphenol (NP), a ubiquitous endocrine disrupting chemical, could impair neurodevelopment and cognitive memory performance. However, whether NP affects the inflammatory responses of MG remains to be elucidated. The aim of this study was to explore the effects of NP on the inflammatory responses of BV2 MG and the underlying mechanisms...
February 27, 2018: Journal of Applied Toxicology: JAT
Yan-Rong Ma, Xuan Luo, Yan-Fang Wu, Tiffany Zhang, Fan Zhang, Guo-Qiang Zhang, Xin-An Wu
The kidney plays a major part in the elimination of many drugs and their metabolites, and drug-induced kidney injury commonly alters either glomerular filtration or tubular transport, or both. However, the renal excretion pathway of drugs has not been fully elucidated at different stages of renal injury. This study aimed to evaluate the alteration of renal excretion pathways in gentamicin (GEN)-induced renal injury in rats. Results showed that serum cystatin C, creatinine and urea nitrogen levels were greatly increased by the exposure of GEN (100 mg kg-1 ), and creatinine concentration was increased by 39...
February 20, 2018: Journal of Applied Toxicology: JAT
Gabriel Adan Araújo Leite, Marciana Sanabria, Marilia Martins Cavariani, Janete Aparecida Anselmo-Franci, Patrícia Fernanda Felipe Pinheiro, Raquel Fantin Domeniconi, Wilma De Grava Kempinas
The increase of obesity, bad eating habits and the lack of physical exercises are highly related to dyslipidemias. Rosuvastatin is a lipid-lowering drug and has been indicated to prevent cardiovascular diseases and to treat dyslipidemias due to its higher efficiency to reduce serum cholesterol concentrations. This study aimed to evaluate the reproductive adverse effects on sexual maturity due to rosuvastatin exposure in juvenile male rats during prepuberty. Three groups were randomly formed with newly weaned rats: control, whose rats received saline solution 0...
February 19, 2018: Journal of Applied Toxicology: JAT
Anca Pop, Tudor Drugan, Arno C Gutleb, Diana Lupu, Julien Cherfan, Felicia Loghin, Béla Kiss
The estrogenic and anti-estrogenic effects of butylparaben (BuPB), butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and propyl gallate (PG) were evaluated for individual compounds as well as for binary mixtures, using an estrogen-dependent reporter gene assay in T47D-Kbluc breast cancer cells and an estrogen-dependent proliferation assay in MCF-7 breast cancer cells. In terms of estrogenicity the potency of the selected compounds increased from BHA < PG < BuPB in the luciferase assay (with BHT showing no significant estrogenic activity), while in the proliferation assay the following order was observed: BHT < BHA < BuPB (with PG showing no significant estrogenic activity)...
February 19, 2018: Journal of Applied Toxicology: JAT
Alison M Pecquet, Jeanelle M Martinez, Melissa Vincent, Neeraja Erraguntla, Michael Dourson
A no-significant-risk-level of 20 mg day-1was derived for tetrabromobisphenol A (TBBPA). Uterine tumors (adenomas, adenocarcinomas, and malignant mixed Müllerian) observed in female Wistar Han rats from a National Toxicology Program 2-year cancer bioassay were identified as the critical effect. Studies suggest that TBBPA is acting through a non-mutagenic mode of action. Thus, the most appropriate approach to derivation of a cancer risk value based on US Environmental Protection Agency guidelines is a threshold approach, akin to a cancer safe dose (RfDcancer)...
February 13, 2018: Journal of Applied Toxicology: JAT
Dragana Samardzija Nenadov, Kristina Pogrmic-Majkic, Svetlana Fa, Bojana Stanic, Aleksandra Tubic, Nebojsa Andric
Humans are exposed not only to single endocrine disruptors, but also to chemical mixtures that can adversely affect their reproductive health. Steroidogenesis in reproductive tissues is emerging as the key target of endocrine disruptor action. Here, we analyzed the effect of environmental chemical mixtures with estrogenic activity on steroidogenic processes in immature rat granulosa cells and whether the observed steroidogenic effects were mediated through estrogen receptors. Extracts from untreated wastewater were prepared by solid-phase extraction and silica gel fractionation...
February 13, 2018: Journal of Applied Toxicology: JAT
Zhan-Ling Liang, Dan-Dan Wu, Yue Yao, Fei-Yuan Yu, Lei Yang, Heng Wee Tan, Machteld N Hylkema, Marianne G Rots, Yan-Ming Xu, Andy T Y Lau
Cadmium (Cd), a carcinogenic toxic metal, is pervasively distributed in the soil, water and air. Chronic exposure to Cd has been correlated to lung disease development including cancers. Although many studies have been conducted to investigate the proteome response of cells challenged with Cd, the epiproteomic responses (i.e., global histone post-translational modifications [PTMs]), particularly in human lung cells, are largely unexplored. Here, we provide an epiproteome profiling of human bronchial epithelial cells (BEAS-2B) chronically treated with cadmium chloride (CdCl2 ), with the aim of identifying global epiproteomic signatures in response to Cd epigenotoxicity...
February 9, 2018: Journal of Applied Toxicology: JAT
Srinivas Chinde, Y Poornachandra, Archana Panyala, Srinivas Indu Kumari, Suresh Yerramsetty, Harikrishna Adicherla, Paramjit Grover
The exigency of semiconductor and super capacitor tungsten oxide nanoparticles (WO3 NPs) is increasing in various sectors. However, limited information on their toxicity and biological interactions are available. Hence, we explored the underlying mechanisms of toxicity induced by WO3 NPs and their microparticles (MPs) using different concentrations (0-300 μg ml-1 ) in human lung carcinoma (A549) cells. The mean size of WO3 NPs and MPs by transmission electron microscopy was 53.84 nm and 3.88 μm, respectively...
February 6, 2018: Journal of Applied Toxicology: JAT
Qiansheng Huang, Yiyao Liu, Sijun Dong
Environmental chemicals (ECs) are drawing great attention to their effects on health and their toxicological mechanisms are being investigated. Long non-coding RNA (lncRNA) is a class of RNA with more than 200 nucleotides and does not have protein coding potential. Recently, it is emerging as a star molecule that participates in a wide range of physiological and pathological processes. It has been reported to be abnormally expressed in diseases. As an epigenetic factor, lncRNAs play an important role in the response of organisms to environmental stress...
February 1, 2018: Journal of Applied Toxicology: JAT
Sarah Taplin, Kapil Vashisht, Markus Walles, David Calise, William Kluwe, Page Bouchard, Robert Johnson
Maytansinoids, the potent cytotoxic derivatives of the alkaloid maytansine are used as payloads in antibody maytansinoid conjugates. This article reviews clinical and preclinical hepatotoxicity observed with antibody maytansinoid conjugates used to treat cancer. Specific aspects of drug distribution, metabolism and excretion that may impact hepatotoxicity are reviewed vis-à-vis the kind of maytansinoid in the conjugate, cleavable or non-cleavable linkers, linker-payload combinations, drug to antibody ratio, metabolite formation, hepatic enzyme induction in relation to drug-drug interactions and species, age and gender differences...
February 1, 2018: Journal of Applied Toxicology: JAT
Yaling Sun, Yingwen Li, Jiedan Rao, Zhihao Liu, Qiliang Chen
Mercury (Hg) is well recognized as a highly toxic substance to fish. Nevertheless, little is known about the toxic effects of Hg on immune organs. In this study, we investigated histology, antioxidant status and immune response of the spleen and head kidney in yellow catfish following 6 weeks of exposure to environmentally relevant concentrations of inorganic Hg (2 and 10 μg l-1 Hg2+ ). As expected, Hg accumulation and histological injury in both tissues were observed. Meanwhile, Hg2+ exposure induced oxidative stress, which increased antioxidant enzyme (superoxide dismutase, catalase and glutathione peroxidase) activities, glutathione content, anti-hydroxyl radical capacity and the expression of genes associated with antioxidant (sod1, cat, gpx1, nrf2 and mt) and stress (hsp70) responses in dose- and tissue-specific manners...
January 30, 2018: Journal of Applied Toxicology: JAT
Wen-Qing Zhu, Pan-Pan Ming, Jing Qiu, Shui-Yi Shao, Ying-Juan Yu, Jia-Xi Chen, Jie Yang, Li-Na Xu, Song-Mei Zhang, Chun-Bo Tang
Titanium (Ti) and its corresponding alloys have been widely applied in dental and orthopedic implants. Owing to abrasion and corrosion of implants in the unfavorable electrolytic aqueous environment of the host body, Ti ions could be released from implants and accumulated in local tissues. Recent studies have found that excessive Ti ions were toxic to osteoblasts in adjacent bone tissues and subsequently influenced long-term effects on implant prostheses. However, the potential molecular mechanisms underlying the damage to osteoblasts induced by Ti ions remained unclear...
January 29, 2018: Journal of Applied Toxicology: JAT
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