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Toxicology Mechanisms and Methods

Dorian S Olivera, Heidi Hoard-Fruchey, Alfred M Sciuto
Therapeutic development against exposure to toxic gases is hindered by the lack of appropriate models to evaluate candidate compounds prior to animal efficacy studies. In this study, an in vitro, air-liquid interface exposure model has been tested to examine its potential application for screening treatments for phosgene (carbonyl chloride)-induced pulmonary injury. Epithelial cultures on Transwell® inserts, combined with a Vitrocell® exposure apparatus, provided a physiologically relevant exposure environment...
October 4, 2016: Toxicology Mechanisms and Methods
Asma Sultana Shaik, Abjal Pasha Shaik, Kaiser Jamil, Abbas H Alsaeed
The cytotoxicity and genotoxicity of pesticide mixtures viz. endosulfan + chlorpyrifos, chlorpyrifos + profenofos, and endosulfan + profenofos were evaluated on cultured human peripheral blood lymphocytes using assays for cell viability, and genotoxicity using chromosomal aberrations test and comet assay. The LC50 values for cytotoxicity were 3.50 μM, 4.18 μM, and 10.5 μM for profenofos, endosulfan, and chlorpyrifos respectively. When combined in equimolar concentrations, the LC50 values for cytotoxicity were 1...
September 7, 2016: Toxicology Mechanisms and Methods
Elaina M Kenyon, Christopher Eklund, John C Lipscomb, Rex A Pegram
A rate for hepatic metabolism (Vmax) determined in vitro must be scaled for in vivo use in a physiologically based pharmacokinetic (PBPK) model. This requires the use of scaling factors such as mg of microsomal protein per gram of liver (MPPGL) and liver mass (FVL). Variation in MPPGL and FVL impacts variation in Vmax, and hence PBPK model-derived estimates of internal dose used in dose response analysis. The impacts of adult human variation in MPPGL and FVL on estimates of internal dose were assessed using a human PBPK model for BDCM, a water disinfection byproduct, for multiple internal dose metrics for two exposure scenarios (single 0...
September 5, 2016: Toxicology Mechanisms and Methods
Latifa Hamdaoui, Manel Naifar, Massara Mzid, Maryem Ben Salem, Amel Chtourou, Fatma Ayedi, Zouhaier Sahnoun, Tarek Rebai
Kalach 360 SL (KL) is a commercial herbicide which contains 360 g/l of Glyphosate used in both agricultural and urban areas throughout the world including Tunisia. We aimed to evaluate the effects of KL on rats' renal system. Female Wistar rats were divided into three groups: group 1 (n = 6) received a standard diet and served as control, groups 2 and 3 (n = 12 each) received 0.07ml (D1: 126 mg/Kg) and 0.175ml (D2: 315mg/Kg) of KL respectively, for 60 days. The chronic exposure to KL induced a significant increase in plasma creatinine, urea and uric acid levels...
September 1, 2016: Toxicology Mechanisms and Methods
Susmita Dutta, Min Bahadur
Buccal micronucleus cytome assay was carried out in 47 exposed (sprayers and leaf harvesters), 47 non-exposed (controls) to determine the extent of damage working in the tea plantations of Terai region of West Bengal, India. As the pesticide exposed male workers were found to consume alcohol and smoked cigarettes/bidis, 35 smokers and 30 alcoholics were also included for comparison. Results showed a significant difference in micronuclei (9.91±2.74, p≤0.001), nuclear bud (4.98±1.31, p≤0.001), binucleate (6...
September 1, 2016: Toxicology Mechanisms and Methods
Shah Md Golam Gousul Azam, Tushar C Sarker, Sabrina Naz
Arsenic (As), a class one carcinogen, reflects a disastrous environmental threat due to its presence in each and every compartment of the environment. The high toxicity of As is notably present in its inorganic forms. Irrigation with As contaminated groundwater in rice fields increases As concentration in topsoil and its bioavailability for rice crops. However, most of the As in paddy field topsoils is present as As(III) form that predominant in rice grain. According to the OECD-FAO, rice is the second most extensively cultivated cereal throughout the world...
August 31, 2016: Toxicology Mechanisms and Methods
Patrick Thomas Gormley, Neal Ingraham Callaghan, Tyson James MacCormack, Christopher Anthony Dieni
Citrated Sprague-Dawley rat blood plasma was used as a biologically relevant exposure medium to assess the acellular toxic potential of two metal oxide engineered nanomaterials (ENMs), zinc oxide (nZnO), and cerium oxide (nCeO2). Plasma was incubated at 37 °C for up to 48 h with ENM concentrations ranging between 0 and 200 mg/L. The degree of ENM-induced oxidation was assessed by assaying for reactive oxygen species (ROS) levels using dichlorofluorescein (DCF), pH, ferric reducing ability of plasma (FRAP), lipase activity, malondialdehyde (MDA), and protein carbonyls (PC)...
August 25, 2016: Toxicology Mechanisms and Methods
Antonio Murgia, Luisa Mancuso, Cristina Manis, Pierluigi Caboni, Giacomo Cao
Human exposure to copper oxide (CuO) nanoparticles (NPs) is rapidly increasing and for this reason reliable toxicity test systems are urgently needed. Recently, the acute cytotoxicity of CuO NPs using the new toxicity test based on human bone marrow mesenchymal stem cells (hBMMSCs) has been evaluated. It was shown that CuO NPs are much more toxic when compared to CuO microparticles (MPs). Several studies associate CuO toxicity to a possible alteration of reactive oxygen species (ROS) system. Unluckily, the mechanism that causes the toxicity is still not clear...
August 23, 2016: Toxicology Mechanisms and Methods
Hamidreza Totonchi, Behnoosh Miladpour, Zohreh Mostafavi-Pour, Fatemeh Khademi, Maryam Kasraeian, Fatemeh Zal
Cigarette smoke is a complex mixture of toxic chemicals, including nicotine, carbon monoxide, and several recognized carcinogens and mutagens. Nicotine has a direct disturbing influence on steroid hormones (estrogen and progesterone), which are essential components of the female reproductive system, but the effect of nicotine on the hormone receptors is not yet clear. The aim of this study was to elucidate the effect of nicotine on the expression of estrogen receptor (ER), progesterone receptor (PR), and vascular endothelial growth factor (VEGF) in endometrial stromal cells...
August 23, 2016: Toxicology Mechanisms and Methods
Kiran Kumar K M, M Naveen Kumar, Rajeshwari H Patil, Rashmi Nagesh, Shubha M Hegde, Kavya K, 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 anti-apoptotic genes; 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 show reduced viability in a dose dependent manner with IC50 of 45µM concentration...
August 15, 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...
August 15, 2016: Toxicology Mechanisms and Methods
Olusola Olalekan Oladipo, Joseph Olusegun Ayo, Suleiman Folorunsho Ambali, Mohammed Bisalla
The study aims to evaluate effects of chronic low-dose co-exposure to lead (Pb), cadmium (Cd) and manganese (Mn) on hepato-renal 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...
August 15, 2016: Toxicology Mechanisms and Methods
Samuel Liebel, Sonia Regina Grötzner, Daniele Dietrich Moura Costa, Marco Antônio Ferreira Randi, Ciro Alberto de Oliveira Ribeiro, Francisco Filipak Neto
Human hepatoma cells (HepG2) were exposed to purified cylindrospermopsin (CYN), a potent toxicant for eukaryotic cells produced by several cyanobacteria. Exposure to 10 μg l(-1) of CYN for 24 h resulted in alteration of expression of 48 proteins, from which 26 were identified through mass spectrometry. Exposure to 100 μg l(-1) of CYN for 24 h affected nuclear area and actin filaments intensity, which can be associated with cell proliferation and toxicity. The proteins are implicated in different biological processes: protein folding, xenobiotic efflux, antioxidant defense, energy metabolism and cell anabolism, cell signaling, tumorigenic potential, and cytoskeleton structure...
August 5, 2016: Toxicology Mechanisms and Methods
Martha Montaño, J Pérez-Ramos, A Esquivel, R Rivera-Rosales, G González-Avila, C Becerril, M Checa, C Ramos
Obesity and emphysema are associated with low-grade systemic inflammation and oxidant stress. Assuming that the oxidant stress induced by emphysema would be decreased by obesity, we analyzed the oxidant/antioxidant state in a rat model combining both diseases simultaneously. Obesity was induced using sucrose, while emphysema by exposure to tobacco smoke. End-points evaluated were: body weight, abdominal fat, plasma dyslipidemia and malondialdehyde (MDA), insulin and glucose AUC, activities of Mn-superoxide dismutase (Mn-SOD), glutathione reductase (GR), glutathione transferase (GST) and glutathione peroxidase (GPx); lung MnSOD and 3-nitrotyrosine (3-NT) immunostaining, and expression of αV and β6 integrin subunits...
July 28, 2016: Toxicology Mechanisms and Methods
Amr A Fouad, Hatem O Qutub, Walid N Al-Melhim
The potential nephroprotection of punicalagin (PNG) against lipopolysaccharide (LPS)-induced acute kidney injury in rats was investigated. Rats received a single i.v. dose of LPS (5 mg/kg), and treated with PNG (50 mg/kg, i.p.), 1 h before, and 1 h following LPS administration. LPS caused significant increases of serum creatinine and neutrophil gelatinase-associated lipocalin. LPS also resulted in significant increases in interleukin-18, tumor necrosis factor-α, interleukin-6, malondialdehyde, nitric oxide, Bax/Bcl-2 ratio and myeloperoxidase, inducible nitric oxide synthase, caspases 3, 8 and 9 activities, and a significant decrease in total antioxidant capacity in kidney tissues...
July 27, 2016: Toxicology Mechanisms and Methods
Ayşe Derya Buluş, Ali Aşci, Pinar Erkekoglu, Aylin Balci, Nesibe Andiran, Belma Koçer-Gümüşel
Exposure to environmental chemicals can affect genetic and epigenetic molecular pathways and may cause altered growth and development. Among those exposures, endocrine-disrupting chemicals (EDCs) are of particular concern as humans are abundantly exposed to these chemicals by various means in every period of life. Several well-known environmental chemicals, including phthalates and bisphenol A (BPA), are classified as EDCs. These EDCs are suggested to play roles in early onset of puberty in girls. The aim of this study is to determine plasma phthalate (di(2-ethylhexyl)phthalate [DEHP] and its main metabolite mono(2-ethylhexyl)phthalate [MEHP]) and urinary BPA levels in girls with idiopathic central precocious puberty (CPP) and peripheral precocious puberty (PPP)...
July 25, 2016: Toxicology Mechanisms and Methods
Huiying Sun, Kaizhong Wang, Haiyan Wei, Zhe Li, Hui Zhao
: Melamine (Mel) is used widely as a basic organic chemical intermediate in several products. Within the last 10 years there have been two high-profile Mel exposures that caused toxicological concern, especially regarding food adulteration. OBJECTIVE: This study aimed to determine the toxicity of Mel and one of its homologs, cyanuric acid (Cya), in vitro and in vivo. MATERIALS AND METHODS: The IC50 of Mel and Cya was determined by the MTT assay in NRK-52E and 293T cell lines...
July 17, 2016: Toxicology Mechanisms and Methods
Laura Escrivá, Guillermina Font, Houda Berrada, Lara Manyes
Compound feed is particularly vulnerable to multi-mycotoxin contamination. A method for the determination of 12 mycotoxins; enniatins A, A1, B, B1; aflatoxins B1, B2, G1, G2; OTA; ZEA; T-2 and HT-2 by liquid chromatography-tandem mass spectrometry has been developed and applied for the analysis of laboratory rat commercial feeds. The method trueness was checked by recovery assays at three different spiked levels (n = 9). Recoveries ranged from 73% to 112%, and the intra-day and inter-day precision were lower than 9% and 13%, respectively...
July 12, 2016: Toxicology Mechanisms and Methods
Xiaoheng Li, Shuyan Cao, Baiping Mao, Yanfang Bai, Xiaomin Chen, Xiudi Wang, Ying Wu, Linxi Li, Han Lin, Qingquan Lian, Ping Huang, Ren-Shan Ge
Butylated hydroxyanisole (BHA) is a synthetic antioxidant used for food preservation. Whether BHA affects testosterone biosynthesis is still unclear. The effects of BHA on the steroidogenesis in rat immature Leydig cells were investigated. Rat immature Leydig cells were isolated from 35-old-day rats and cultured with BHA (50 μM) for 3 h in combination with 22R-OH-cholesterol, pregnenolone, progesterone, androstenedione, testosterone or dihydrotestosterone, and the concentrations of 5α-androstanediol and testosterone in the media were measured...
July 7, 2016: Toxicology Mechanisms and Methods
Aziz Eftekhari, Elham Ahmadian, Yadollah Azarmi, Alireza Parvizpur, Hamed Hamishehkar, Mohammad Ali Eghbal
The hepatotoxic effects of the antipsychotic agent, risperidone (RIS) were investigated for better understanding the pathogenesis of RIS in liver toxicity in vivo and in in vitro. Isolated rat hepatocytes were obtained by collagenase perfusion technique and were then incubated with RIS, different antioxidants in particular coenzyme Q10 (CoQ10), N-acetyl cysteine (NAC). Our results showed that RIS could induce cytotoxicity via rising reactive oxygen species (ROS), mitochondrial potential collapse, lysosomal membrane leakiness, GSH depletion and lipid peroxidation...
July 7, 2016: Toxicology Mechanisms and Methods
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