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Toxicology Mechanisms and Methods

Durgesh Nandini Das, Prashanta Kumar Panda, Prajna Paramita Naik, Subhadip Mukhopadhyay, Niharika Sinha, Sujit K Bhutia
Polycyclic aromatic hydrocarbons (PAHs) comprise the major class of cancer-causing chemicals and are ranked ninth among the chemical compounds threatening to humans. Moreover, interest in PAHs has been mainly due to their carcinogenic property, these compounds are genotoxic, teratogenic, mutagenic, and carcinogenic. Polymorphism in cytochrome P450 (CYP450) and aryl hydrocarbon receptor (AhR) have the capacity to convert procarcinogens into carcinogens, which is an imperative factor contributing to individual susceptibility to cancer development...
December 5, 2016: Toxicology Mechanisms and Methods
Mathan Kumar S, Madhumitha Haridoss, Kavitha Swaminathan, Ramesh Kumar G, Dahn L Clemens, Aparajita Dey
Alcohol mediated liver injury is associated with changes in the level of the major cellular antioxidant glutathione (GSH). It is interesting to investigate if the changes in intracellular GSH level through exogenous agents affect the intracellular cysteine content and the protein adduct formation indicative of oxidative insult in chronic alcohol treated liver cells. In VL-17A cells treated with 2 mM N- acetyl cysteine (NAC) or 0.1 mM ursodeoxycholic acid (UDCA) plus 100 mM ethanol, an increase in cysteine concentration which was accompanied by decreases in hydroxynonenal (HNE) and glutathionylated protein adducts were observed...
December 4, 2016: Toxicology Mechanisms and Methods
Yong Fa Zhang, Jian Ying Yang, Yong Kai Li, Wei Zhou
To explore the toxic mechanism of T-2 toxin on Leydig cells of mice, we would investigate the toxicity and oxidative stress induced by T-2 toxin in the cells. Leydig cells were isolated and cultured with control or T-2 toxin (10(-7) M, 10(-8) M, or 10(-9) M) for 24 h, then cells and supernatants were harvested to examine cell viability, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities, expression of messenger RNA (mRNA) related to oxidative stress, malondialdehyde (MDA) content and DNA damage...
November 29, 2016: Toxicology Mechanisms and Methods
Jiao Jiang, Henggui Xu, Hetong Wang, Yining Zhang, Ping Ya, Chun Yang, Fasheng Li
Benzo(a)pyrene (BaP) was a well-known environmental pollutant, numerous studies had implicated BaP as a causative agent in human cancer, particularly lung cancer.The lemongrass essential oil (LEO) possessed various pharmacological activities, especially the anti-oxidative stress and cancer prevention. In the current study, human embryonic lung fibroblast (HELF) cells were treated with 25 mM BaP in the absence or presence of 0.5%, 1% or 2.5% LEO and the cell viability and levels of oxidative stress and DNA damage in the cells were then measured...
November 28, 2016: Toxicology Mechanisms and Methods
Virginia Tzankova, Cvetelina Gorinova, Magdalena Kondeva-Burdina, Rumiana Simeonova, Stanislav Philipov, Spiro Konstantinov, Petar Petrov, Dimitar Galabov, Krassimira Yoncheva
To evaluate the safety profile of cationic micelles, based on triblock copolymer poly(dimethylaminoethyl methacrylate)-poly(e-caprolactone)-poly(dimethylaminoethyl methacrylate) (PDMAEMA9- PCL70-PDMAEMA9), the effects of empty (PM) and curcumin loaded micelles (PM-Curc) on nonenzyme induced lipid peroxidation (LPO) in vitro, hemolytic activity and morphological changes in some organs after repeated intraperitoneal administration in vivo were studied. To induce LPO, rat liver microsomes were incubated with a solution of iron sulfate and ascorbinic acid (Fe(2+)/AA)...
November 16, 2016: Toxicology Mechanisms and Methods
Anna Barbasz, Magdalena Oćwieja, Stanisław Walas
The growing popularity of nanomaterials requires a systematic study of their effects on the human body. Silver nanoparticles (AgNPs), due to their antiseptic properties, are used in almost every area of life. The purpose of the study was to examine whether the precursor used for the synthesis of nanoparticles affects their bio-influence and modifies their impact on cells of the human immune system. To compare the effects of precursor silver salts (AgNO3, CH3COOAg and AgClO4) and corresponding nanoparticles (TAN TAA and TAC) cytotoxicity study was conducted on two cell lines U-937 and HL-60...
November 15, 2016: Toxicology Mechanisms and Methods
Lei Bao, Jie Zu, Qianqian He, Hui Zhao, Su Zhou, Xinchun Ye, Xinxin Yang, Kun Zan, Zuohui Zhang, Hongjuan Shi, Guiyun Cui
CONTEXT: Studies have shown that thrombin activation played a central role in cell injuries associated with intracerebral hemorrhage (ICH). OBJECTIVE: Here, our study investigated the cytotoxicity of thrombin on neurons, and determined the involvement of JNK pathways in thrombin-induced neuronal apoptosis. MATERIALS AND METHODS: Primary cultured neurons were treated with different doses of thrombin. Some neurons were given either SP600125 or vehicle...
November 14, 2016: Toxicology Mechanisms and Methods
Somayeh Shahani, Farzaneh Behzadfar, Danial Jahani, Maryam Ghasemi, Fatemeh Shaki
BACKGROUND AND PURPOSE: Gentamicin (GM) is used against bacterial infections. The aim of our investigation was to evaluate the role of inflammation and also oxidative damage in nephrotoxic potential of GM and protective effects of Nasturtium officinale (watercress) against GM-induced nephrotoxicity in Wistar rats. MATERIAL AND METHOD: The animals were divided into eight groups: control, solvent, GM (80 mg/kg IP), GM with three doses (50,100, 200 mg/kg/day) of hydroalcoholic extract of watercress and one group only received high dose of extract and a group which received gentamicin plus vitamin E for 10 consecutive days...
November 8, 2016: Toxicology Mechanisms and Methods
Chunlei Yu, Xiaojie Sun, Yingcai Niu
Curcuma phaeocaulis Val. is a Chinese medicinal herb that is contraindicated during pregnancy for over a thousand years in China. The aims of the present study were to evaluate the effect of curcumol (one of the major components of C. phaeocaulis Val.) on neurite outgrowth and characterize the signal transduction pathways in PC12 cells. Curcumol significantly inhibited neurite outgrowth and cell proliferation, but did not cause cell death at a concentration of 450 μM in differentiated PC12 cells. In addition, curcumol evoked oxidative stress and it was indicated by an elevation in reactive oxygen species (ROS) and lipid peroxidation (LPO)...
November 6, 2016: Toxicology Mechanisms and Methods
K M Kiran Kumar, M Naveen Kumar, Rajeshwari H Patil, Rashmi Nagesh, Shubha M Hegde, K Kavya, R L Babu, Govindarajan T Ramesh, S Chidananda Sharma
Cadmium (Cd) is one of the well-known highly toxic environmental and industrial pollutants. Cd first accumulates in the nucleus and later interacts with zinc finger proteins of antiapoptotic genes and inhibit the binding of transcriptional factors and transcription. However, the role of Cd in oxidative stress and apoptosis is less understood. Hence, the present study was undertaken to unveil the mechanism of action. A549 cells were treated with or without Cd and cell viability was measured by MTT assay. Treatment of cells with Cd shows reduced viability in a dose-dependent manner with IC50 of 45 μM concentration...
November 6, 2016: Toxicology Mechanisms and Methods
Dan Lou, Qiaochu Wang, Min Huang, Zhijun Zhou
Epidemiological studies have revealed that environmentally relevant low levels of paraquat (PQ) exposure is listed on the etiology of neurological disorders such as Parkinson's disease (PD). The behavioral effects of PQ are of current interest, especially when exposure occurs in the period of early stage of life. To characterize whether and how age affects neurobehavioral performances of mice after PQ exposure, 21 days postnatal (PN21) and adult male C57BL/6 mice were daily administrated by oral gavage with 0 mg/kg (saline, control), 5 mg/kg or 10 mg/kg of PQ for 28 consecutive days...
November 6, 2016: Toxicology Mechanisms and Methods
Olusola Olalekan Oladipo, Joseph Olusegun Ayo, Suleiman Folorunsho Ambali, Bisalla Mohammed
The study aims to evaluate effects of chronic low-dose coexposure to lead (Pb), cadmium (Cd) and manganese (Mn) on hepatorenal toxicity and oxidative stress. Young male Wistar rats were treated with Pb acetate (1.4 mg/kg BW), Cd chloride (0.01 mg/kg BW), Mn chloride (0.14 mg/kg BW) and their combination (Pb + Cd + Mn) by oral gavage, for 15 weeks. Liver enzymes, albumin (Alb), globulin (Glb), total protein, creatinine, urea and electrolyte concentrations were measured in the serum. Hepatic and renal malondialdehyde (MDA), glutathione peroxidase-1 (GPx1) and metallothionein-1 (MT1) concentrations were measured by enzyme immunoassay technique...
November 6, 2016: Toxicology Mechanisms and Methods
Mitra Abbasi, Ben G Small, Nikunjkumar Patel, Masoud Jamei, Sebastian Polak
BACKGROUND AND PURPOSE: To determine the predictive performance of in silico models using drug-specific preclinical cardiac electrophysiology data to investigate drug-induced arrhythmia risk (e.g. Torsade de Pointes (TdP)) in virtual human subjects. EXPERIMENTAL APPROACH: To assess drug proarrhythmic risk, we used a set of in vitro electrophysiological measurements describing ion channel inhibition triggered by the investigated drugs. The Cardiac Safety Simulator (CSS V2...
November 4, 2016: Toxicology Mechanisms and Methods
Kevin A Ford, Gregory Ryslik, Bryan K Chan, Sock-Cheng Lewin-Koh, Davi Almeida, Michael Stokes, Stephen R Gomez
The goal of this investigation was to perform a comparative analysis on how accurately 11 routinely-used in silico programs correctly predicted the mutagenicity of test compounds that contained either bulky or electron-withdrawing substituents. To our knowledge this is the first study of its kind in the literature. Such substituents are common in many pharmaceutical agents so there is a significant need for reliable in silico programs to predict precisely whether they truly pose a risk for mutagenicity. The predictions from each program were compared to experimental data derived from the Ames II test, a rapid reverse mutagenicity assay with a high degree of agreement with the traditional Ames assay...
November 4, 2016: Toxicology Mechanisms and Methods
Abeer Hassanin, Yoshio Kaminishi, Takao Itakura
This study planned to isolation and characterization of AKR1A1 cDNA from Bap injected nile tilapia (Oreochromis niloticus), comparison of its characteristic structures with those of other species, characterization of AKR1A1 gene and promoter, and investigation of AKR1A1 mRNA expression in various organs of Bap injected tilapia. The cDNA was 1172 bp long which includes an open reading frame of 975 bp encoding a 324 amino acids protein and a stop codon. The sequence showed 3' and 5' non-coding regions of 179 and 18 bp...
November 1, 2016: Toxicology Mechanisms and Methods
Esra Emerce, Ismet Cok, Sibel Sari, Omur Bostanci
Hydrochlorothiazide is a widely used antihypertensive agent and one of its major impurities, salamide (4-amino-6-chlorobenzene-1,3-disulphonamide), has a chemical structure containing a primary amino group, a functional group that has previously been reported to be associated with carcinogenic activity. It is known that hydrochlorothiazide purity is a challenging problem for the pharmaceutical industry. As there were no prior mutagenicity data for the impurity salamide, the aim was to investigate its mutagenicity in this study...
October 28, 2016: Toxicology Mechanisms and Methods
João Soeiro Teodoro, Ana Patrícia Gomes, Ana Teresa Varela, Filipe Valente Duarte, Anabela Pinto Rolo, Carlos Marques Palmeira
Diabetes and associated conditions are now considered a worldwide epidemic, with increasing costs and burdens with no cure yet developed. The chitin-derived glucosamine biopolymer chitosan has shown promising results when supplied to diabetic patients. However, no study has investigated the possible toxic side effects of chitosan treatments, in particular when regarding the most important bioenergetic organelle, mitochondria. As such, we aimed to understand if supplementation of chitosan to the diet of normal and diabetic rats could compromise mitochondrial function on two of the major organs involved in diabetes, obesity, and metabolic regulation, the liver and skeletal muscle...
October 28, 2016: Toxicology Mechanisms and Methods
Ozlem Ozsoy, Sinem Aras, Ayse Ozkan, Hande Parlak, Burcu Gemici, Nimet Uysal, Mutay Aslan, Piraye Yargicoglu, Aysel Agar
The aim of this study was to investigate the possible toxic effects of sulfite on neurons by measuring active avoidance learning in normal and sulfite oxidase (SOX)-deficient aged rats. Twenty four months of age Wistar rats were divided into four groups: control (C), sulfite-treated group (S), SOX-deficient group (D) and SOX-deficient + sulfite-treated group (DS). SOX deficiency was established by feeding rats with a low molybdenum (Mo) diet and adding 200 ppm tungsten (W) to their drinking water. Sulfite in the form of sodium metabisulfite (25 mg/kg) was given by gavage for six weeks...
October 28, 2016: Toxicology Mechanisms and Methods
Faisal Imam, Naif O Al-Harbi, Mohammad Matar Al-Harbi, Mushtaq Ahmad Ansari, Mashal M Almutairi, Musaad Alshammari, Talal Saad Almukhlafi, Mohd Nazam Ansari, Khaldoon Aljerian, Sheikh Fayaz Ahmad
Carfilzomib (CFZ), is a potent, selective second generation proteasome inhibitor, used for the treatment of multiple myeloma. The aim of the present study was to investigate the possible protective effect of apremilast (AP) on the CFZ -induced cardiotoxicity. Rats were randomly divided into four groups: Group 1, served as the control group, received normal saline. Group 2, served as the toxic group, received CFZ (4 mg/kg, intraperitoneally [i.p.]). Groups 3 and 4, served as treatment groups, and received CFZ with concomitant oral administration of AP in doses of 10 and 20 mg/kg/day, respectively...
October 27, 2016: Toxicology Mechanisms and Methods
Hala M Abdelkarem, Laila M Fadda, Omyma R Kaml
The purpose of this study was to evaluate the potential protective effect of qurecetin (Qur) and α-lipolic acid (ALA) to modulate the perturbation of bone turnover which is induced by nano-zinc oxide (n-ZnO). Rats were fasted overnight and randomly divided into two groups: G1, normal healthy animals and the other rats were administered zinc oxide nanoparticles orally by guava in a dose of 600 mg/kg body weight/d for 5 sequential days in Wistar albino male rats. N-ZnO-exposed animals were randomly sub-divided into three groups: G2, n-ZnO-exposed animals; G3, n-ZnO-exposed animals co-treated with Qur (200 mg/kg daily); and G4, n-ZnO-exposed animals co-treated with ALA (200 mg/kg)...
October 27, 2016: Toxicology Mechanisms and Methods
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