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Toxicology

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https://www.readbyqxmd.com/read/28433638/metabolomic-analysis-for-combined-hepatotoxicity-of-chlorpyrifos-and-cadmium-in-rats
#1
Ming-Yuan Xu, Pan Wang, Ying-Jian Sun, Yi-Jun Wu
Pesticides and heavy metals are widespread environmental pollutants. Although the acute toxicity of organophosphorus pesticide chlorpyrifos (CPF) and toxic heavy metal cadmium (Cd) is well characterized, the combined toxicity of CPF and Cd, especially the hepatotoxicity of the two chemicals with long-term exposure at a low dose, remained unclear. In this study, we investigated the toxicity in the liver of rats upon subchronic exposure to CPF and Cd at environmentally relevant doses. Rats were given three different doses (1/135 LD50, 1/45 LD50 and 1/15 LD50) of CPF and Cd as well as their mixtures by oral gavage for 90 days...
April 19, 2017: Toxicology
https://www.readbyqxmd.com/read/28412278/disruption-of-glutamate-neurotransmitter-transmission-is-modulated-by-snap-25-in-benzo-a-pyrene-induced-neurotoxic-effects
#2
Kai Yang, Xuejun Jiang, Qiuping Su, Jing Wang, Chunlin Li, Yinyin Xia, Shuqun Cheng, Qizhong Qin, Xianqing Cao, Chengzhi Chen, Baijie Tu
Benzo[a]pyrene (B[a]P), a ubiquitous chemical contaminant in the environment, is a well-established neurotoxicant to human. However, the molecular mechanisms for B[a]P neurotoxicity are still unclear. In the present study, after treating Sprague-Dawley rats with 0.02, 0.2 and 2.0mg/kg/day B[a]P for 7 weeks [from postnatal day (PND) 5 to PND54], our results showed that B[a]P exposure caused a significant deficits in learning and memory function. By using U87 cells as in vitro model, the significant cytotoxicity and the induction of apoptosis caused by B[a]P were further verified...
April 18, 2017: Toxicology
https://www.readbyqxmd.com/read/28427893/study-of-acetylcholinesterase-activity-and-apoptosis-in-sh-sy5y-cells-and-mice-exposed-to-ethanol
#3
Wenjun Sun, Liangjing Chen, Wei Zheng, Xiaoan Wei, Wenqi Wu, Ellen G Duysen, Wei Jiang
Ethanol is one of the most commonly abused psychotropic substances with deleterious effects on the central nervous system. Ethanol exposure during development results in the loss of neurons in brain regions and when exposed to ethanol cultured cells undergo apoptosis. To date no information is available on whether abnormally high AChE activity is characteristic of apoptosis in animals exposed to ethanol. The aims of the present study were to determine whether induction of AChE activity is associated with ethanol-induced apoptosis and to explore the mechanism of enhanced AChE activity induced by ethanol...
April 17, 2017: Toxicology
https://www.readbyqxmd.com/read/28395993/salinomycin-attenuates-liver-cancer-stem-cell-motility-by-enhancing-cell-stiffness-and-increasing-f-actin-formation-via-the-fak-erk1-2-signalling-pathway
#4
Jinghui Sun, Qing Luo, Lingling Liu, Xianjiong Yang, Shunqin Zhu, Guanbin Song
Salinomycin has recently been identified as an antitumour drug for several types of cancer stem cell (CSC) treatments. However, the effects of salinomycin on the migratory and invasive properties of liver cancer stem cells (LCSCs) are unclear. In present study, we investigated the effect of salinomycin on the migration and invasion of LCSCs, and examined the molecular mechanisms underlying the anticancer effects of salinomycin. Here we showed that the migration and invasion of LCSCs were significantly suppressed in a salinomycin dose-dependent manner...
April 8, 2017: Toxicology
https://www.readbyqxmd.com/read/28395994/thujone-inhibits-the-function-of-%C3%AE-7-nicotinic-acetylcholine-receptors-and-impairs-nicotine-induced-memory-enhancement-in-one-trial-passive-avoidance-paradigm
#5
Ahmed Sultan, Keun-Hang Susan Yang, Dmitro Isaev, Eslam El Nebrisi, Nurulain Syed, Nadia Khan, Christopher F Howarth, Bassem Sadek, Murat Oz
Effects of thujone, a major ingredient of absinthe, wormwood oil and some herbal medicines, were tested on the function of α7 subunit of the human nicotinic acetylcholine (α7 nACh) receptor expressed in Xenopus oocytes using the two-electrode voltage-clamp technique. Thujone reversibly inhibited ACh (100μM)-induced currents with an IC50 value of 24.7μM. The effect of thujone was not dependent on the membrane potential and did not involve Ca(2+)-dependent Cl(-) channels expressed endogenously in oocytes...
April 7, 2017: Toxicology
https://www.readbyqxmd.com/read/28390928/itraconazole-cis-diastereoisomers-activate-aryl-hydrocarbon-receptor-ahr-and-pregnane-x-receptor-pxr-and-induce-cyp1a1-in-human-cell-lines-and-human-hepatocytes
#6
Martina Stepankova, Barbora Pastorkova, Petr Bachleda, Zdenek Dvorak
Triazole antimycotic itraconazole contains in its structure three chiral centres; therefore, it forms eight stereoisomers. Commercial preparations of itraconazole are a mixture of four cis-diastereoisomers. There is much evidence that efficacy, adverse effects, and toxicity of chiral drugs may be stereospecific. Therefore, we have prepared 4 pure cis-diastereoisomers of itraconazole and investigated their effects on transcriptional activities of xenoreceptors aryl hydrocarbon receptor AhR and pregnane X receptor PXR...
April 5, 2017: Toxicology
https://www.readbyqxmd.com/read/28385499/the-induction-of-cytochrome-p450-2e1-by-ethanol-leads-to-the-loss-of-synaptic-proteins-via-ppar%C3%AE-down-regulation
#7
Shufang Na, Jie Li, Huibo Zhang, Yueran Li, Zheqiong Yang, Yanjun Zhong, Guicheng Dong, Jing Yang, Jiang Yue
Ethanol, one of the most commonly abused substances throughout history, is a substrate and potent inducer of cytochrome P450 2E1 (CYP2E1). Our previous study showed that brain CYP2E1 was induced by chronic ethanol treatment and was associated with ethanol-induced neurotoxicity in rats. We therefore investigated the possible mechanism of brain CYP2E1 involvement in ethanol-induced neurodegeneration. Compared with the controls, chronic ethanol treatment (3.0g/kg, i.g., 160 days) significantly increased CYP2E1 mRNA levels in the rat cortex, but the mRNA levels of peroxisome proliferator-activated receptor α (PPARα) and the pre- and post-synaptic proteins (synaptophysin, SYP, and drebrin1, DBN1) were decreased...
April 3, 2017: Toxicology
https://www.readbyqxmd.com/read/28366820/immune-related-gene-polymorphisms-in-pulmonary-diseases
#8
REVIEW
Dhirendra P Singh, Prathyusha Bagam, Malaya K Sahoo, Sanjay Batra
Between the DNA sequences of two randomly-selected human genomes, which consist of over 3 billion base pairs and twenty five thousand genes, there exists only 0.1% variation and 99.9% sequence identity. During the last couple of decades, extensive genome-wide studies have investigated the association between single-nucleotide polymorphisms (SNPs), the most common DNA variations, and susceptibility to various diseases. Because the immune system's primary function is to defend against myriad infectious agents and diseases, the large number of people who escape serious infectious diseases underscores the tremendous success of this system at this task...
March 30, 2017: Toxicology
https://www.readbyqxmd.com/read/28347754/cadmium-disrupts-autophagic-flux-by-inhibiting-cytosolic-ca-2-dependent-autophagosome-lysosome-fusion-in-primary-rat-proximal-tubular-cells
#9
Fei Liu, Xin-Yu Wang, Xu-Ping Zhou, Zong-Ping Liu, Xiang-Bin Song, Zhen-Yong Wang, Lin Wang
Previous studies have shown that subcellular Ca(2+) redistribution is involved in Cd-induced autophagy inhibition in primary rat proximal tubular (rPT) cells, but the mechanism remains unclear. In this study, the status of autophagic flux was monitored by the GFP and RFP tandemly tagged LC3 method. Pharmacological inhibition of cytosolic Ca(2+) concentration ([Ca(2+)]c) with 2-APB or BAPTA-AM significantly alleviated Cd-elevated yellow puncta formation and restored Cd-inhibited red puncta formation, while thapsigargin (TG) had the opposite regulatory effect, demonstrating that Cd-induced [Ca(2+)]c elevation inhibited the autophagic flux in rPT cells...
March 25, 2017: Toxicology
https://www.readbyqxmd.com/read/28344095/early-detection-clinical-diagnosis-and-management-of-lung-disease-from-exposure-to-diacetyl
#10
Cecile S Rose
Inhalation of diacetyl-containing products is associated with risk for occupational bronchiolitis obliterans (BO) and fixed airways obstruction, particularly in workers exposed to heated liquids and powdered formulations. This review describes the occupational settings in which diacetyl-related lung disease has been reported and the clinical presentation of disease, along with an approach to diagnosis and management. The importance of early disease recognition, appropriate removal from exposure, and medical monitoring to optimize prognosis is reviewed...
March 23, 2017: Toxicology
https://www.readbyqxmd.com/read/28342779/suppression-of-calpain-expression-by-nsaids-is-associated-with-inhibition-of-cell-migration-in-rat-duodenum
#11
Kristopher Silver, A Littlejohn, Laurel Thomas, Bhupinder Bawa, James D Lillich
Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for the alleviation of pain and inflammation, but these drugs are also associated with a suite of negative side effects. Gastrointestinal (GI) toxicity is particularly concerning since it affects an estimated 70% of individuals taking NSAIDs routinely, and evidence suggests the majority of toxicity is occurring in the small intestine. Traditionally, NSAID-induced GI toxicity has been associated with indiscriminate inhibition of cyclooxygenase isoforms, but other mechanisms, including inhibition of cell migration, intestinal restitution, and wound healing, are likely to contribute to toxicity...
March 22, 2017: Toxicology
https://www.readbyqxmd.com/read/28341147/cadmium-stimulates-myofibroblast-differentiation-and-mouse-lung-fibrosis
#12
Xin Hu, Jolyn Fernandes, Dean P Jones, Young-Mi Go
Increasing evidence suggests that Cd at levels found in the human diet can cause oxidative stress and activate redox-sensitive transcription factors in inflammatory signaling. Following inflammation, tissue repair often involves activation of redox-sensitive transcription factors in fibroblasts. In lungs, epithelial barrier remodeling is required to restore gas exchange and barrier function, and aberrant myofibroblast differentiation leads to pulmonary fibrosis. Contributions of exogenous exposures, such as dietary Cd, to pulmonary fibrosis remain incompletely defined...
March 21, 2017: Toxicology
https://www.readbyqxmd.com/read/28323003/pulsed-or-continuous-electromagnetic-field-induce-p53-p21-mediated-apoptotic-signaling-pathway-in-mouse-spermatogenic-cells-in-vitro-and-thus-may-affect-male-fertility
#13
Przemyslaw Solek, Lena Majchrowicz, Dominika Bloniarz, Ewelina Krotoszynska, Marek Koziorowski
The impact of electromagnetic field (EMF) on the human health and surrounding environment is a common topic investigated over the years. A significant increase in the electromagnetic field concentration arouses public concern about the long-term effects of EMF on living organisms associated with many aspects. In the present study, we investigated the effects of pulsed and continuous electromagnetic field (PEMF/CEMF) on mouse spermatogenic cell lines (GC-1 spg and GC-2 spd) in terms of cellular and biochemical features in vitro...
March 16, 2017: Toxicology
https://www.readbyqxmd.com/read/28315715/sab-mediates-mitochondrial-dysfunction-involved-in-imatinib-mesylate-induced-cardiotoxicity
#14
Tara P Chambers, Luis Santiesteban, David Gomez, Jeremy W Chambers
Imatinib mesylate is an effective treatment for chronic myelogenous leukemia and gastrointestinal stromal tumors. Although imatinib mesylate is highly tolerable, it has been implicated in severe congestive heart failure in mouse models and patients. A hallmark of imatinib mesylate-induced cardiotoxicity is mitochondrial dysfunction. The mitochondrial scaffold Sab has been implicated in facilitating signaling responsible for mitochondrial dysfunction in a c-Jun N-terminal Kinase (JNK)-dependent manner. We examined the impact of Sab-mediated signaling on imatinib mesylate cardiotoxicity in H9c2 rat cardiomyocyte-like cells...
March 16, 2017: Toxicology
https://www.readbyqxmd.com/read/28315714/cadmium-induced-malignant-transformation-of-rat-liver-cells-potential-key-role-and-regulatory-mechanism-of-altered-apolipoprotein-e-expression-in-enhanced-invasiveness
#15
Masayo Suzuki, Shuso Takeda, Noriko Teraoka-Nishitani, Akane Yamagata, Takahiro Tanaka, Marika Sasaki, Natsuki Yasuda, Makiko Oda, Tatsuji Okano, Kazuhiro Yamahira, Yuta Nakamura, Takanobu Kobayashi, Katsuhito Kino, Hiroshi Miyazawa, Michael P Waalkes, Masufumi Takiguchi
Cadmium is a transition metal that is classified as human carcinogen by the International Agency for Research on Cancer (IARC) with multiple target sites. Many studies using various model systems provide evidence of cadmium-induced malignancy formation in vivo or malignant cell transformation in vitro. Nonetheless, further studies are needed to completely understand the mechanisms of cadmium carcinogenicity. Our prior studies have utilized a rat liver epithelial cell line (TRL 1215) as a model for cadmium-induced malignant transformation...
March 16, 2017: Toxicology
https://www.readbyqxmd.com/read/28315349/diethylstilbestrol-induces-oxidative-dna-damage-resulting-in-apoptosis-of-spermatogonial-stem-cells-in-vitro
#16
Khaled Habas, Martin H Brinkworth, Diana Anderson
The spermatogonial stem cells (SSCs) are the only germline stem cells in adults that are responsible for the transmission of genetic information from mammals to the next generation. SSCs play a very important role in the maintenance of progression of spermatogenesis and help provide an understanding of the reproductive biology of future gametes and a strategy for diagnosis and treatment of infertility and male reproductive toxicity. Androgens/oestrogens are very important for the suitable maintenance of male germ cells...
March 14, 2017: Toxicology
https://www.readbyqxmd.com/read/28288859/mitochondrial-toxicity-of-perfluorooctane-sulfonate-in-mouse-embryonic-stem-cell-derived-cardiomyocytes
#17
Lei-Lei Tang, Jia-Dan Wang, Ting-Ting Xu, Zhe Zhao, Jia-Jie Zheng, Ren-Shan Ge, Dan-Yan Zhu
Perfluorooctane sulfonate (PFOS) is a persistent organic contaminant that may cause cardiotoxicity in animals and humans. However, little is known about the underlying mechanism by which it affects the organelle toxicity in cardiomyocytes during the cardiogenesis. Our previous proteomic study showed that differences of protein expression mainly existed in mitochondria of cardiomyocytes differentiated from embryonic stem (ES) cells after exposure to PFOS. Here, we focused on mitochondrial toxicity of PFOS in ES cell-derived cardiomyocytes...
March 10, 2017: Toxicology
https://www.readbyqxmd.com/read/28288858/the-margin-of-internal-exposure-moie-concept-for-dermal-risk-assessment-based-on-oral-toxicity-data-a-case-study-with-caffeine
#18
Jos G M Bessems, Alicia Paini, Monika Gajewska, Andrew Worth
Route-to-route extrapolation is a common part of human risk assessment. Data from oral animal toxicity studies are commonly used to assess the safety of various but specific human dermal exposure scenarios. Using theoretical examples of various user scenarios, it was concluded that delineation of a generally applicable human dermal limit value is not a practicable approach, due to the wide variety of possible human exposure scenarios, including its consequences for internal exposure. This paper uses physiologically based kinetic (PBK) modelling approaches to predict animal as well as human internal exposure dose metrics and for the first time, introduces the concept of Margin of Internal Exposure (MOIE) based on these internal dose metrics...
March 10, 2017: Toxicology
https://www.readbyqxmd.com/read/28286206/simplified-qpcr-method-for-detecting-excessive-mtdna-damage-induced-by-exogenous-factors
#19
Artem P Gureev, Ekaterina A Shaforostova, Anatoly A Starkov, Vasily N Popov
Damage to mitochondrial DNA (mtDNA) is a meaningful biomarker for evaluating genotoxicity of drugs and environmental toxins. Existing PCR methods utilize long mtDNA fragments (∼8-10kb), which complicates detecting exact sites of mtDNA damage. To identify the mtDNA regions most susceptible to damage, we have developed and validated a set of primers to amplify ∼2kb long fragments, while covering over 95% of mouse mtDNA. We have modified the detection method by greatly increasing the enrichment of mtDNA, which allows us solving the problem of non-specific primer annealing to nuclear DNA...
March 9, 2017: Toxicology
https://www.readbyqxmd.com/read/28286205/ochratoxin-a-induced-premature-senescence-in-human-renal-proximal-tubular-cells
#20
Xuan Yang, Sheng Liu, Chuchu Huang, Haomiao Wang, Yunbo Luo, Wentao Xu, Kunlun Huang
Ochratoxin A (OTA) has many nephrotoxic effects and is a promising compound for the study of nephrotoxicity. Human renal proximal tubular cells (HKC) are an important model for the study of renal reabsorption, renal physiology and pathology. Since the induction of OTA in renal senescence is largely unknown, whether OTA can induce renal senescence, especially at a sublethal dose, and the mechanism of OTA toxicity remain unclear. In our study, a sublethal dose of OTA led to an enhanced senescent phenotype, β-galactosidase staining and senescence associated secretory phenotype (SASP)...
March 9, 2017: Toxicology
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