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Toxicology Mechanisms and Methods

Gopala Krishna, Gopa Gopalakrishnan, Saryu Goel
Neuroleptic drug molindone hydrochloride is a dopamine D2/D5 receptor antagonist and it is in late stage development for the treatment of impulsive aggression in children and adolescents who have attention deficient/hyperactivity disorder (ADHD). This new indication for this drug would expand the target population to include younger patients, and therefore, toxicity assessments in juvenile animals were undertaken in order to determine susceptibility differences, if any, between this age group and the adult rats...
January 31, 2017: Toxicology Mechanisms and Methods
Deborah Navit de Carvalho Cavalcante, Juliana Caroline Vivian Sposito, Bruno do Amaral Crispim, André Vieira do Nascimento, Alexeia Barufatti Grisolia
Nuclear abnormalities (micronuclei and meta-nuclear changes) have been used as biomarkers to identify cell damages. As children are more vulnerable to the adverse effects of pollution in relation to adults, assessing genetic damage caused by environmental influences is of great interest. As such, the objective was to determine metanuclear (karyolysis, pycnosis, karyorrhexis, binucleated cells, chromosome bridges, and micronuclei) in cells from the oral mucosa of children associated with the school environment, gender, exposure to cigarette smoke and vehicular traffic...
January 29, 2017: Toxicology Mechanisms and Methods
Alessandro de Souza Prestes, Matheus Mülling Dos Santos, Assis Ecker, Daniela Zanini, Maria Rosa Chitolina Schetinger, Denis Broock Rosemberg, João Batista Teixeira da Rocha, Nilda Vargas Barbosa
Methylglyoxal (MG) is a reactive dicarbonyl metabolite originated mainly from glucose degradation pathway that plays an important role in the pathogenesis of diabetes mellitus. Reactions of MG with biological macromolecules (proteins, DNA and lipids) can induce cytotoxicity and apoptosis. Here, human erythrocytes, leukocytes and platelets were acutely exposed to MG at concentration ranging from 0.025 to 10 mM. Afterwards, hemolysis and osmotic fragility in erythrocytes, DNA damage and cell viability in leukocytes, and the activity of purinergic ecto-nucleotidases in platelets were evaluated...
January 22, 2017: Toxicology Mechanisms and Methods
Xiaowen Jiang, Xinxin Feng, Hui Huang, Lin Liu, Lu Qiao, Binqing Zhang, Wenhui Yu
Rotenone has been used as a pesticide for many years, it is an environmental poison reported to cause neurological diseases. However, the effects of rotenone on the rat liver are unclear, as are the mechanisms of toxicity. In the present study, Sprague-Dawley (SD) rats were divided into five groups: control, dimethyl sulfoxide (DMSO), rotenone low-dose (1 mg/kg), rotenone mid-dose (2 mg/kg) and rotenone high-dose (4 mg/kg). The treatments were orally administered daily for 28 days, we assessed health status, mRNA expression levels of inflammatory factors, protein levels, nitric oxide (NO) content and histological changes...
January 22, 2017: Toxicology Mechanisms and Methods
Manal F Elkhadragy, Ahmed E Abdel Moneim
This study investigated the protective effect of Fragaria ananassa methanolic extract on cadmium chloride (CdCl2)-induced hepatotoxicity in rats. CdCl2 was intraperitoneally injected at a dose of 6.5 mg/kg of body weight for 5 days with or without methanol extract of Fragaria ananassa (250 mg/kg). The hepatic cadmium concentration, lipid peroxidation, nitric oxide, glutathione content and antioxidant enzyme activities, including superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase, were estimated...
January 22, 2017: Toxicology Mechanisms and Methods
Isha Nagpal, Suresh K Abraham
The main objective of our present work was to ascertain the efficacy of Drosophila melanogaster model for assessing antigenotoxic and antioxidant effects of dietary phytochemicals gallic acid (GA), quercetin (QC) and limonene (Lim) against urethane (URE), a genotoxic environmental carcinogen. Oregon-K (ORK) adult male flies were fed GA, QC and Lim in combination with URE (20 mM) in 10% sucrose for 72 h. Third instar larvae were fed instant medium containing the above phytochemicals and URE for 24 h. Sex-linked recessive lethal (SLRL) test and assays for estimating glutathione content (GSH), glutathione S-transferase (GST), catalase (CAT), superoxide dismutase (SOD) and lipid peroxidation (MDA content) were performed...
January 18, 2017: Toxicology Mechanisms and Methods
A R Nisha, H Hazilawati, M L Mohd Azmi, M M Noordin
Polycyclic aromatic hydrocarbons (PAHs) are persistent pollutants and chemically a class of structurally similar chemical compounds characterized by the presence of fused aromatic rings. This research was undertaken to find out immunotoxic effects produced by pyrene, phenanthrene and fluoranthene. These chemicals were injected into developing chicks at three dose levels (0.2, 2 and 20 mg per kg) through allantioc route to rule out possible mechanisms involved in immunotoxicity. DNA adduct produced by PAHs in immune organs were analyzed by DNA adduct enzyme-linked immunosorbent assay (ELISA) kit and DNA damage was assessed by comet assay...
January 18, 2017: Toxicology Mechanisms and Methods
Ángel Rodríguez-Huamán, Sandra Casimiro-Gonzales, Jorge Antonio Chávez-Pérez, Carla Gonzales-Arimborgo, Richard Cisneros-Fernández, Luis Ángel Aguilar-Mendoza, Gustavo F Gonzales
Reactive oxygen species (ROS) are normally produced during cell metabolism, there is strong evidence to suggest that ROS produced in excess impair the cell and may be etiologically related to various neurodegenerative diseases. This study was undertaken to examine the effects of Lepidium meyenii (MACA) methanol leaf extract on neurotoxicity in PC12 cell exposed to 6-hydroxydopamine (6-OHDA). Fresh samples of "maca" leaves were processed in order to obtain foliar extracts and to evaluate the neurobiological activity on PC12 cells, subjected to the cytotoxic effect of 6-OHDA through the determination of the capacity antioxidant, cell viability and cytotoxicity assays on PC12 cells...
January 8, 2017: Toxicology Mechanisms and Methods
Yin He, Dehong Tan, Bing Bai, Zhaoxia Wu, Shujuan Ji
The potent neurotoxic agent acrylamide (ACR) is formed during Maillard reaction in food processing. Epigallocatechin-3-gallate (EGCG), a major bioactive component of green tea, is an antioxidant, but its effects on ACR-induced neurotoxicity are unclear. Here, we investigated the neuroprotective effects of EGCG against ACR-induced apoptosis and astrogliosis in the cerebral cortex. Rats were pretreated with EGCG for 4 d and then co-administered ACR for 14 d. Immunohistochemical analysis of glial fibrillary acidic protein and 8-hydroxy-2'-deoxyguanosine indicated that EGCG attenuated astrogliosis and DNA damage in ACR treated rats...
January 5, 2017: Toxicology Mechanisms and Methods
Jin Yang, Ying Wan, Hui Liu, Jirui Bi, Youjin Lu
Noncardiogenic lung edema is a key factor affecting the prognosis of acute lung injury (ALI). Previous studies have been focused on regulatory roles of ceramide on lung vascular endothelial barrier functions and had already identified ceramide as mediator involved in the formation of lung edema. However, the effects of ceramide on lung epithelial barrier were still unknown. This study aimed to investigate the effects of ceramide on the barrier function of alveolar epithelial cells. Primary mouse alveolar type II epithelial cells (AECII) were grown on Transwell polyester membranes to construct monolayer, and stimulated with different concentrations of ceramide...
January 4, 2017: Toxicology Mechanisms and Methods
Jiri Kassa, Jan Misik, Jana Hatlapatkova, Jana Zdarova Karasova
The ability of two newly developed bispyridinium oximes (K920, K923) to reduce tabun-induced acute neurotoxic signs and symptoms was compared with the oxime K203 and trimedoxime using a functional observational battery. The neuroprotective effects of the oximes studied combined with atropine on rats poisoned with tabun at a sublethal dose (130 μg/kg i.m.; 80% of LD50 value) were evaluated. Tabun-induced neurotoxicity was monitored by functional observational battery at 2 hours after tabun administration...
January 2, 2017: Toxicology Mechanisms and Methods
Harikiran Lingabathula, Narsimhareddy Yellu
The study investigated the oxidative stress induction by the 10 and 25 nm silver nanorods (SNRs) following intra-tracheal instillation in rats after 1 day, 1 week, 1 month and 3 months post instillation periods at 1 and 5 mg/kg b.w. doses. The blood was withdrawn by retro orbital plexus method after exposure periods and different oxidative stress markers were estimated. The results showed that the both sizes of SNRs induced increased levels of MDA and depleted GSH levels after 1 day and 1 week post exposure periods...
December 28, 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 (OS) and DNA damage in the cells were then measured...
December 28, 2016: Toxicology Mechanisms and Methods
Reda Massawe, Leon Drabo, Margaret Whalen
Pentachlorophenol (PCP) and dichlorodiphenyltrichloroethane (DDT) are pesticides that have been widely used and significantly contaminate the environment. Both are found in human blood and have been shown to alter the lytic and binding function of human natural killer (NK) cells. Interferon gamma (IFNγ) and tumor necrosis factor alpha (TNFα) are pro-inflammatory cytokines which regulate immune responsiveness to pathogens and tumors. Their levels require very tight control to prevent loss of immune competence or excessive inflammation...
December 26, 2016: Toxicology Mechanisms and Methods
Aktarul Islam Siddique, Vijay Mani, Sivaranjani Arivalagan, Nisha Susan Thomas, Namasivayam Nalini
Asiatic acid (AA), a pentacyclic triterpenoid derived from the tropical medicinal plant Centella asiatica is known to exhibit numerous pharmacological properties. We hypothesized that AA will have chemopreventive potential against 1,2-dimethylhydrazine (DMH)-induced experimental colon carcinogenesis in male Wistar rats. Rats were arbitrarily divided into six groups. Group I rats were processed as control. Group II rats received AA (8 mg/kg b.w., p.o.) and groups III-VI rats received subcutaneous injections of DMH (20 mg/kg b...
December 22, 2016: Toxicology Mechanisms and Methods
S Mathan Kumar, Madhumitha Haridoss, Kavitha Swaminathan, Ramesh Kumar Gopal, Dahn 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 21, 2016: Toxicology Mechanisms and Methods
Yongjie Tian, Yixin Lu, Xiuju Xu, Chao Wang, Tianqi Zhou, Xiangming Li
Two yeast enhanced green fluorescence protein (yEGFP) yeast reporter vectors, pR1558-yEGFP and pR406-yEGFP, which are regulated by two RAD54 promoters containing 406-bp and 1558-bp DNA sequences, respectively, were constructed using molecular biological techniques and transformed into yeast for the screening of genotoxins. The constructed biosensors were named W303-1A/R1558-yEGFP and W303-1A/R406-yEGFP. To quantify biosensor performance, both transformed yeast cells were exposed to multiple doses of genotoxins including methylmethane sulfonate (MMS; a DNA alkylating agent), 4-nitroquinoline-N-oxide (4-NQO; a DNA cleavage agent), 5-fluorouracil (5-Fu; an inhibitor of polymerases and topoisomerases) and colchicine and canavanine (affecting other biochemical activities)...
December 20, 2016: Toxicology Mechanisms and Methods
Mahshid Hodjat, Maryam Baeeri, Mohammad Amin Rezvanfar, Mahban Rahimifard, Mahdi Gholami, Mohammad Abdollahi
Ethephon is one of the most widely used plant growth regulator in agriculture that its application has been increased in recent years. Many reports have raised concern over the safety of this organophosphorus compound. The aim of the current study was to assess the potential genotoxic effect of ethephon on murine embryonic fibroblast (MEF)cell line, using two genotoxicity endpoints; γH2AX expression and comet assay. γH2AX served as an early and sensitive biomarker of genotoxic damage. Oxidative stress biomarkers, including reactive oxygen species (ROS), lipid peroxidation (LPO) and total antioxidant capacity were also examined...
December 20, 2016: Toxicology Mechanisms and Methods
Mohemmed Faraz Khan, M Mumtaz Alam, Garima Verma, Wasim Akhtar, Moshahid A Rizvi, Asif Ali, Mymoona Akhter, M Shaquiquzzaman
Dioxins and dioxin like compounds (DLCs) are the ones with poor water solubility and low volatility, resistant to physical, chemical and biological processes, persistent in the environment even under extreme conditions. Due to lipophilic nature, they get adhered to the fatty material and concentrate through biomagnification and bioaccumulation, thereby easily getting incorporated into food chains, paving the way to endocrine disruption via modulation of various human receptors. This in turn leads to certain adverse health effects...
December 20, 2016: Toxicology Mechanisms and Methods
Yuxiu Gu, Shanshan Cheng, Gui Chen, Yuexin Shen, Xiyue Li, Qin Jiang, Juan Li, Yi Cao
It was recently shown that ZnO nanoparticles (NPs) could induce endoplasmic reticulum (ER) stress in human umbilical vein endothelial cells (HUVECs). If ER stress is associated the toxicity of ZnO NPs, the presence of ER stress inducer thapsigargin (TG) should alter the response of HUVECs to ZnO NP exposure. In this study, we addressed this issue by assessing cytotoxicity, oxidative stress and inflammatory responses in ZnO NP exposed HUVECs with or without the presence of TG. Moreover, TiO2 NPs were used to compare the effects...
December 20, 2016: Toxicology Mechanisms and Methods
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