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Toxicology Mechanisms and Methods

Xianjun Liu, Tingting Zhang, Xiang Li, Ge Zhao, Fuwei Xie
2-amino-9H-pyrido[2,3-b]indole (AαC), which is a hazardous compound present in cigarette smoke, has been listed as probable human carcinogens (Group 2B). The carcinogenicity and genotoxicity of AαC were activated by the process of metabolic bio-activation. Whereas, few studies about genotoxicity induced by AαC have been reported. In this study, we took HepG2 cells as the model to investigate the relationship between oxidative DNA damage induced by AαC and metabolic bio-activation of AαC, which is of importance to unveil the mechanism of AαC genotoxicity...
October 12, 2017: Toxicology Mechanisms and Methods
Abhishek Albert, Vidhi Tiwari, Eldho Paul, Sasikumar Ponnusamy, Divya Ganesan, Rajkumar Prabhakaran, Selvi Mariaraj Sivakumar, Selvam Govindan Sadasivam
Experimental induction of hyperoxaluria by ethylene glycol (EG) administration is disapproved as it causes metabolic acidosis while the oral administration of chemically synthesized potassium oxalate (KOx) diet does not mimic our natural system. Since existing models comprise limitations, the present study is aimed to develop an improved model for the induction of dietary hyperoxaluria and nephrocalcinosis in experimental rats by administration of naturally available oxalate rich diet. Male albino Wistar rats were divided into five groups...
October 5, 2017: Toxicology Mechanisms and Methods
Yuvraj Dange, Somnath Bhinge, Vijay Salunkhe
A simple, rapid, and robust RP-HPLC method have been developed and validated to measure Palbociclib and Letrozole at single wavelength (254 nm). A isocratic elution of samples performed on Intersil C8 (4.6 mm x 250 mm particle size 5 μm) column with mobile phase consisting 0.02M sodium dihydrogen phosphate buffer (pH 5.5): acetonitrile: methanol (80: 10: 10 v/v/v) delivered at flow rate 1.0 mL min(-1). A good linear response was achieved over the range of 5-50 μg mL(-1). The LODs for Palbociclib and Letrozole were found to be 0...
October 5, 2017: Toxicology Mechanisms and Methods
Daniel P Katz, Mohammed Majrashi, Sindhu Ramesh, Manoj Govindarajulu, Dwipayan Bhattacharya, Subhrajit Bhattacharya, Aiman Shalgum, Chastity Bradford, Vishnu Suppiramaniam, Jack Deruiter, C Randall Clark, Muralikrishnan Dhanasekaran
Benzylpiperazine has been designated as Schedule I substance under the Controlled Substances Act by Drug Enforcement Administration. Benzylpiperazine is a piperazine derivative, elevates both dopamine and serotonin extracellular levels producing stimulatory and hallucinogenic effects, respectively, similar to methylenedioxymethamphetamine (MDMA). However, the comparative neurotoxic effects of Piperazine derivatives (Benzylpiperazine and Benzoylpiperazine) have not been elucidated. Here, piperazine derivatives (Benzylpiperazine and Benzoylpiperazine) were synthesized in our lab and the mechanisms of cellular-based neurotoxicity were elucidated in a dopaminergic human neuroblastoma cell line (SH-SY5Y)...
September 5, 2017: Toxicology Mechanisms and Methods
Camelia Oprean, Alexandra Ivan, Florina Bojin, Mirabela Cristea, Codruta Soica, Lavinia Drăghia, Angela Caunii, Virgil Paunescu, Calin Tatu
Products of natural origin have become important agents in the treatment of cancer, and the active principles of natural sources could be used in combination with chemotherapeutic agents to increase their effects and to minimize their toxicity. Oleanolic (OA) and ursolic (UA) acids are intensely studied for their promising anticancer potential. The aim of this study was focused on the in vitro toxicological effects induced by UA and OA human mesenchymal stem cells and on melanoma, one of the most frequent cancers whose incidence is increasing every year...
September 3, 2017: Toxicology Mechanisms and Methods
Yining Li, Cao Zhang, Liangliang Liu, Yu Gong, Yixi Xie, Yi Cao
Recent study suggested that the presence of phytochemicals in food could interact with nanoparticles (NPs) and consequently reduce the toxicity of NPs, which has been attributed to the antioxidant properties of phytochemicals. In this study, we investigated the interactions between ZnO NPs and two flavonoids baicalein (Ba) or baicalin (Bn) as well as the influence of the interactions on the toxicity of ZnO NPs to Caco-2 cells. The antioxidant properties of Ba and Bn were confirmed by DPPH and ABTS assays, with Ba being stronger...
September 3, 2017: Toxicology Mechanisms and Methods
Gustavo F Gonzales, Jennifer Tello, Alisson Zevallos-Concha, Luis Baquerizo, Lidia Caballero
Sacha inchi is a nut produced in the Peruvian Amazonian and its oil is recognized by the lowering lipids effect in humans. The remaining material transformed to flour has a higher amount of protein, but, the nitrogen balance once ingested orally has not been studied. The present study was designed to evaluate the nitrogen balance after single consumption of 30 g of sacha inchi flour and compared with that obtained after consumption of 30 g soybean flour in adult men and women. This was a double-blind cohort study in 15 men and 15 women between 18-55 years old...
August 30, 2017: Toxicology Mechanisms and Methods
Sherin Ramadan Hamad, Hanan Ramadan Mohamed
Nowadays gastric ulcers become very common gastrointestinal disorders and numerous natural plant extracts exert promising anti-ulcerative effects. Therefore, this study was designed to evaluate the possible protective effect of dietary starch against ethanol induced gastric ulcers in mice. Post-administration of dietary starch for three consecutive days caused remarkable ameliorations in hemorrhagic lesions in gastric mucus and significant suppression in % incidence of ulceration, ulcer index and ulcer score induced by ethanol single administration...
August 29, 2017: Toxicology Mechanisms and Methods
E H Yeo, W L Goh, S C Chow
The leucine aminopeptidase inhibitor, benzyloxycarbonyl-leucine-chloromethylketone (z-L-CMK) was found to be toxic and readily induced cell death in Jurkat T cells. Dose-response studies show that lower concentration of z-L-CMK induced apoptosis in Jurkat T cells whereas higher concentration causes necrosis. In z-L-CMK-induced apoptosis, both the initiator caspases (-8 and -9) and effector caspases (-3 and -6) were processed to their respective subunits. However, the caspases remained intact in z-L-CMK-induced necrosis...
August 29, 2017: Toxicology Mechanisms and Methods
F Zal, F Khademi, R Taheri, Z Mostafavi-Pour
Oxidative stress and a disrupted antioxidant system are involved in a variety of pregnancy complications. In the present study, the role of vitamin E (Vit E) and folate as radical scavengers on the GSH homeostasis in stress oxidative induced in rat endometrial cells was investigated. Primary endometrial stromal cell cultures treated with 50 and 200 µM of H2O2 and evaluated the cytoprotective effects of Vit E (5 µM) and folate (0.01 µM) in H2O2 treated cells for 24 h. Following the exposure of endometrial cells to H2O2 alone and in the presence of Vit E and/or folate, cell survival, glutathione peroxidase (GPx) and glutathione reductase activities and the level of reduced glutathione (GSH) were measured...
August 29, 2017: Toxicology Mechanisms and Methods
Panhong Gou, Xiaoling Qi, Rui Yuan, Haojie Li, Xiaoling Gao, Junling Wang, Benzhong Zhang
The aim of this study is to identify the role of Tet1-mediated DNA demethylation in the neurotoxicity caused by unconjugated bilirubin (UCB) in vitro. Primary neuronal cells after cultured for 72 h were exposed to UCB (0-100 μmol/L) for 24 h. Following exposure to UCB cytotoxicity was determined with the methyl tetrazolium (MTT) assay, reactive oxygen species (ROS) and caspase-3 activity in neuron cells were measured with the corresponding assay kits. The expression of Tet1 and Klotho was determined with RT-PCR at mRNA level and western blot at protein level...
August 25, 2017: Toxicology Mechanisms and Methods
Jayme P Coyle, Robert J Rinaldi, Giffe T Johnson, Marie M Bourgeois, James McCluskey, Raymond D Harbison
Acrolein is a reactive α,β-unsaturated aldehyde known for its adduction to endogenous biomolecules, resulting in initiation or exacerbation of several disease pathways. In-vitro systems are routinely used to elucidate the cytotoxic or mechanistic role(s) of acrolein in pathogenesis. Nevertheless the half-life of acrolein in biological or in-vitro systems, e.g., blood or culture media, has not been well characterized. Since in-vitro cytotoxic and mechanistic investigations routinely expose cultures to acrolein from 1 hour to 72 hours, we aimed to characterize the half-life of acrolein in culture medium to ascertain the plausible exposure window...
August 22, 2017: Toxicology Mechanisms and Methods
Xudong Liu, Yuchao Zhang, Ruliu Wu, Meng Ye, Yuqing Zhao, Jun Kang, Ping Ma, Jinquan Li, Xu Yang
Alzheimer's disease (AD) is a serious, common, global disease, yet its etiology and pathogenesis are incompletely understood. Although an association between AD and exposure to air pollutants has been discussed, the effects of pollutants on the functioning of the brain remain unclear. The indoor environment is where exposure to formaldehyde (FA) can occur. Whether exposure to FA contributes to the development of AD needs to be investigated. To determine the objective, C57BL/6 mice were exposed daily to FA (0, 0...
August 16, 2017: Toxicology Mechanisms and Methods
Bahareh Sadat Yousefsani, Jalal Pourahmad, Hossein Hosseinzadeh
In this study, we want to understand whether crocin could prevent mitochondrial damage caused by As III. For this purpose, we determined different mitochondrial toxicity endpoints caused by As III. We evaluated mitochondrial ROS formation, lipid peroxidation, mitochondrial membrane potential collapse, mitochondrial outer membrane integrity and cytochrome c release. Our results showed that pretreatment with crocin at a concentration of 25 µg/ml significantly (P < 0.001) reduced As III induced mitochondrial ROS formation, lipid peroxidation, mitochondrial membrane potential collapse and mitochondrial swelling...
August 16, 2017: Toxicology Mechanisms and Methods
Shalini D, Senthilkumar S, Rajaguru P
The multi-industrial applications of zinc oxide nanomaterials (ZnO NMs) lead to increasing exposure to humans. Though the ZnO nanoparticles toxicity had been evaluated previously, toxicity of other forms of ZnO nanomaterials has not been evaluated. In this study, cytotoxicity and genotoxicity of four different types of ZnO NMs were evaluated using human peripheral blood lymphocytes (HPBL). In addition, the effect of anti-oxidants on ZnO NMs induced toxicity was also evaluated. Our results suggest that, size and shape of the nanomaterials have profound effects on their toxicity...
August 13, 2017: Toxicology Mechanisms and Methods
Mohammad Hadi Zarei, Seyed Farshad Hosseini Shirazi, Marjan Aghvami, Ahmad Salimi, Jalal Pourahmad
Nickel compounds possess many applications in different industrial processes. Human beings are exposed to nickel commonly through occupational exposure and food. Although a few studies so far have investigated the effects of nickel compounds on human lymphocytes, the complete mechanism of cytotoxicity of this metal on human lymphocytes is yet to be determined. The intention of this paper was to determine the cytotoxicity mechanism of water soluble NiCl2 towards human lymphocytes using the accelerated cytotoxicity mechanisms screening (ACMS) technique...
August 4, 2017: Toxicology Mechanisms and Methods
Ziheng Wei, Qingqing Qian, Xu Dong, Na Li, Guangchun Sun, Songyan Gao, Xin Dong
Veratrum nigrum L. (VN) is a poisonous traditional Chinese medicine herb present since thousands of years in China. Clinical studies have shown that VN has the ability to cause hepatotoxicity, which severely limits its clinical use. The mechanism of its hepatotoxicity has not been fully elucidated. The purpose of this study was to develop and characterize a model of acute and chronic hepatotoxicity induced by Veratrum nigrum L. extract (VNE) to understand the mechanism of liver tissue metabolomics approach using on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOFMS)...
July 28, 2017: Toxicology Mechanisms and Methods
Edna Carolina Pizzato, Marcelo Filonzi, Hemerson Silva da Rosa, André Valle de Bairros
The presence of exogenous testosterone has been monitored mainly in the urine and blood. However, other biological matrices such as hair, nail, and saliva samples can be used successfully for in vivo measurement. Chromatographic analysis requires pretreatment to obtain free testosterone and its metabolites. Among the pretreatment procedures, digestion, hydrolysis and solvolysis steps are conducted to reach the analytical purpose. Digestion assay is indicated for hair and nail samples. First, it is recommended to perform the decontamination step...
July 28, 2017: Toxicology Mechanisms and Methods
Fariba Nabatchian, Afshin Moradi, Mahmoud Aghaei, Mustafa Ghanadian, Seyyed Mehdi Jafari, Samineh Tabesh
Euphorbia species have been used in traditional medicine in many countries for the treatment of cancer. This article aims to evaluate the capability of a new lathyrane diterpene isolated from Euphorbia aellenii to induce apoptosis in the Caov-4 cell line to determine the underlying mechanism of its anticancer effects. A new 6(17)-epoxylathyrane diterpenes: aellinane from Euphorbia aellenii was evaluated for viability of Caov-4 cells by MTT method. Apoptosis induction by lathyrane diterpene was confirmed by annexin V-FITC/PI staining, and caspase-6 activation...
July 28, 2017: Toxicology Mechanisms and Methods
Andreas F Lehner, Margaret Johnson, John Buchweitz
Dried blood spots (DBS) on filter paper provide a simple and convenient means of collecting, storing and shipping samples for veterinary diagnostics related to toxin exposures. This paper presents validation data on analysis of DBS for chlorinated persistent organic pollutants, specifically 4,4'-dichloro-diphenyl-trichloroethane (4,4'-DDT) and its breakdown product 4,4'-dichlorodiphenyl-dichloroethylene (4,4'-DDE), lindane and a representative polychlorinated biphenyl (PCB) congener PCB-153. Analysis was by gas chromatography with electron capture detection (GC-ECD)...
July 26, 2017: Toxicology Mechanisms and Methods
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