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Toxicology Mechanisms and Methods

Rewan Kanode, Saurabh Chandra, Sharad Sharma
Non-genotoxic carcinogens may play a significant role in development of cancer. Currently short-term assays for mutagenicity classify genotoxic carcinogens and lack the abilities to detect epigenetic carcinogens. The need to develop an endpoint always remains to recognize potentially carcinogenic agents employing rapid and practical bioassays. For this, the present study utilized TA98 and TA1537 tester strains of Salmonella typhimurium to evaluate four non-genotoxic carcinogenic agents (Coumarin, β-Myrcene, Bis(2-ethylhexyl) phthalate and trans-anethole)...
March 22, 2017: Toxicology Mechanisms and Methods
Imen Jaballi, Hajer Ben Saad, Intidhar Bkhairia, Intissar Kammoun, Michael Droguet, Christian Magné, Tahia Boudawara, Choumous Kallel, Monsef Nasri, Ahmed Hakim, Ibtissem Ben Amara
BACKGROUND AND PURPOSE: The aim of this study was to elucidate the biochemical, molecular and histopathological aspects of the kidney injuries as well as the hematological perturbations induced after adult mice exposure to increasing doses of maneb (MB). MATERIAL AND METHOD: Adult mice were intraperitoneally treated for seven days with four graded doses of MB, corresponding to 1/8, 1/6, 1/4 and 1/2 of its lethal dose (LD50=1500 mg/kg body weight). RESULTS: Hematological analysis revealed a significant disruption in total white blood cells and platelets and a significant decrease in the plasmatic levels of ferrozine in mice treated with 1/8, 1/6 and 1/4 of MB LD50...
March 21, 2017: Toxicology Mechanisms and Methods
Apurva Koul, Suresh K Abraham
Saffron (SAF), the dried stigmas of Crocus sativus is commonly used for flavouring and coloring food. Studies on bioactivity of SAF have demonstrated its in vivo antioxidant activity. The aim of our study was to assess the impact of SAF intake on γ-radiation (RAD) induced: (a) chromosomal damage, (b) oxidative stress in liver and brain and (c) histopathological effects in the intestinal cells and male germ cells in mice. Freeze-dried aqueous extract of SAF was used for the experiments. Our preliminary cell-free DNA nicking assay using pBR322 DNA revealed protective effects of freeze-dried SAF extract against hydroxyl radical induced DNA damage...
March 15, 2017: Toxicology Mechanisms and Methods
Zülal Atlı Şekeroğlu, Büşra Güneş, Seval Kontaş Yedier, Vedat Şekeroğlu, Birsen Aydın
The color additive, tartrazine (TRZ), is widely used in food products, drugs and cosmetics. Genotoxicity of TRZ and its metabolites has not been investigated in detail in the presence and absence of a metabolic activator (S9 mix) in human. Therefore, the aim of this study is to investigate the cytotoxic and genotoxic effects of TRZ and its metabolites on cultured human lymphocytes by using chromosome aberration (CA) and micronucleus (MN) tests. Cultures were treated with 625, 1250 and 2500 μg/ml of TRZ in the presence and absence of S9 mix...
March 7, 2017: Toxicology Mechanisms and Methods
Susan Hall, Shailendra Anoopkumar-Dukie, Gary D Grant, Ben Desbrow, Richard Lai, Devinder Arora, Yinna Hong
Chemotherapy is an important treatment modality for malignancy but is limited by significant toxicity and it susceptibility to numerous drug interactions. While the interacting effects with medications are well known, there is limited evidence on the interaction with commonly consumed food and natural products. The aim of this study was to evaluate the bioactive constituents of coffee (caffeine and chlorogenic acid) on the cytotoxicity of doxorubicin, gemcitabine, and paclitaxel in vitro. Pretreatment with caffeine (100 nM and 10 μM) sensitized SH-SY5Y cells to doxorubicin-induced toxicity and increased apoptosis and sensitized PC3 cells to gemcitabine-induced toxicity...
March 6, 2017: Toxicology Mechanisms and Methods
Wang Zhang, Xin-Yue Shen, Wen-Wen Zhang, Hao Chen, Wei-Ping Xu, Wei Wei
Diethylhexyl phthalate (DEHP) is suspected to be an inevitable factor related to metabolic disease. Our previous study demonstrated that excess DEHP could exacerbate non-alcoholic fatty liver disease (NAFLD) in SD rats. Addressing the terra incognita in DEHP-induced metabolic dysfunction, this study used HepG2 cells to investigate the potential mechanisms involved in DEHP-induced toxicity in vitro. The cells were established lipid overload model with oleic acid and BSA, then exposed to different concentrations (5, 10, 25, 50, 100 μmol/l DEHP) of DEHP for further analysis...
February 1, 2017: 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
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 malondialdehyde (MDA) and depleted glutathione (GSH) levels after 1 day and 1 week post exposure periods...
January 25, 2017: Toxicology Mechanisms and Methods
Jin Yang, Ying Wang, 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 24, 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
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 22, 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 (FOB). 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 FOB at 2 h after tabun administration. The results indicate that all tested oximes combined with atropine enable tabun-poisoned rats to survive till the end of experiment while one non-treated tabun-poisoned rat died within 2 h...
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
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...
January 11, 2017: Toxicology Mechanisms and Methods
Zülal Atlı Şekeroğlu, Haluk Kefelioğlu, Seval Kontaş Yedier, Vedat Şekeroğlu, Berrin Delmecioğlu
There has been considerable debate about the relationship between epilepsy and cancer. Oxcarbazepine (OXC) is used for treating certain types of seizures in patients with epilepsy. There have been no detailed investigations about genotoxicity of OXC and its metabolites. Therefore, the aim of this study is to investigate the cytotoxic and genotoxic effects of OXC and its metabolites on cultured human lymphocytes. The cytotoxicity and genotoxicity of OXC on human peripheral blood lymphocytes were examined in vitro by sister chromatid exchange (SCE), chromosomal aberration (CA) and micronucleus (MN) tests...
January 11, 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
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