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Drug and Chemical Toxicology

Haluk Kefelioğlu, Zülal Atlı Şekeroğlu, Gamze Coşguner, Seval Kontaş Yedier, Vedat Şekeroğlu
It has been stated that some antipsychotic drugs might cause genotoxic and carcinogenic effects. Ziprasidone (ZIP) is commonly used an antipsychotic drug. However, its genotoxicity and carcinogenicity data are very limited. The cytotoxicity and genotoxicity of ZIP on human peripheral blood lymphocytes were examined in vitro by sister chromatid exchange (SCE), chromosome aberration (CA) and micronucleus (MN) tests in this study. Lymphocyte cultures were treated with 50, 75 and 100 μg/ml of ZIP in the presence and absence of a metabolic activator (S9 mix)...
November 29, 2016: Drug and Chemical Toxicology
Seyed Reza Fatemi Tabatabaie, Babak Mehdiabadi, Najmeh Mori Bakhtiari, Mohammad Reza Tabandeh
CONTEXT: Maternal exposure to silver nanoparticles (AgNPs) affects neurobehavioral reflexes and spatial memory formation in offspring. Although the transmission of AgNPs into the brain has been reported, its toxic effect on dopamine metabolism in the brain of offspring has not been studied so far. OBJECTIVE: The aim of the present study was to investigate the expression levels of tyrosine hydroxylase (TH) and monoamine oxidase A (MAO-A) genes in the brain of offspring exposed in utero to various concentrations of AgNPs...
November 24, 2016: Drug and Chemical Toxicology
Mine Senyildiz, Buket Alpertunga, Sibel Ozden
3-Monochloropropane-1,2-diol (3-MCPD) is a well-known food processing contaminant that has been regarded as a rat carcinogen, which is known to induce Leydig-cell and mammary gland tumors in males, as well as kidney tumors in both genders. 3-MCPD is highly suspected to be a non-genotoxic carcinogen. 2,3-Epoxy-1-propanol (glycidol) can be formed via dehalogenation from 3-MCPD. We aimed to investigate the cytotoxic effects of 3-MCPD and glycidol, then to demonstrate the possible epigenetic mechanisms with global and gene-specific DNA methylation in rat kidney epithelial cells (NRK-52E)...
November 24, 2016: Drug and Chemical Toxicology
Gizem Bor, Muhammed Üçüncü, Mustafa Emrullahoğlu, Aysel Tomak, Gülşah Şanlı-Mohamed
Recently, development of fluorescent nanoparticle-based probes for various bioimaging applications has attracted great attention. This work aims to develop a new type fluorescent nanoparticle conjugate and evaluate its cytotoxic effects on A549 and BEAS 2B cell lines. Throughout the study, ionically crosslinked chitosan nanoparticles (CNs) were conjugated with carboxylated 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY-COOH). The results of conjugates (BODIPY-CNs) were investigated with regard to their physic-chemical, optical, cytotoxic properties and cellular internalization...
November 21, 2016: Drug and Chemical Toxicology
Abhishek Basu, Arin Bhattacharjee, Amalesh Samanta, Sudin Bhattacharya
Cisplatin (CDDP) is one of the first-line anticancer drugs that has gained widespread use against various forms of human malignancies. But, the therapeutic outcome of CDDP therapy is limited due to its adverse effects including myelotoxicity and DNA damage which may lead to the subsequent risk of developing secondary cancer. Hence, in search of a suitable cytoprotectant, this study investigated the probable protective efficacy of an oxovanadium(IV) complex, namely oxovanadium(IV)-L-cysteine methyl ester complex (VC-IV) against CDDP-induced myelosuppression and genotoxic damage in the bone marrow cells of Swiss albino mice...
November 20, 2016: Drug and Chemical Toxicology
Ana Paula de Souza, Mauricio Lehmann, Rafael Rodrigues Dihl
Metal complexes are still broadly used as the first line of the treatment for different types of tumors nowadays. Carboplatin and oxaliplatin were authorized for clinical use, even though there is little information on the mutagenic profile associated to their usage. This study evaluated the cytostatic effects and the induction of complex genomic alterations after 24-h treatment of CHO-K1 cells to concentrations of 12.5-800 μM of carboplatin and oxaliplatin in the cytokinesis-block micronucleus assay (CBMN-Cyt)...
November 20, 2016: Drug and Chemical Toxicology
Soumaya Kilani-Jaziri, Imen Mokdad-Bzeouich, Mounira Krifa, Nouha Nasr, Kamel Ghedira, Leila Chekir-Ghedira
Many studies have been performed to assess the potential utility of natural products as immunomodulatory agents to enhance host responses and to reduce damage to the human body. To determine whether phenolic compounds (caffeic, ferulic, and p-coumaric acids) have immunomodulatory effects and clarify which types of immune effector cells are stimulated in vitro, we evaluated their effect on splenocyte proliferation and lysosomal enzyme activity. We also investigated the activity of natural killer (NK) cells and cytotoxic T lymphocytes (CTL)...
November 18, 2016: Drug and Chemical Toxicology
Kyoung Ho Oh, Yoon Chan Rah, Kyu Ho Hwang, Seung Hoon Lee, Soon Young Kwon, Jae Hyung Cha, June Choi
CONTEXT: Ototoxicity due to medications, such as aminoglycosides, is irreversible, and free radicals in the inner ear are assumed to play a major role. Because melatonin has an antioxidant property, we hypothesize that it might mitigate hair cell injury by aminoglycosides. OBJECTIVE: The objective of this study was to evaluate whether melatonin has an alleviative effect on neomycin-induced hair cell injury in zebrafish (Danio rerio). METHODS: Various concentrations of melatonin were administered to 5-day post-fertilization zebrafish treated with 125 μM neomycin for 1 h...
November 18, 2016: Drug and Chemical Toxicology
Yasuhiro Tsubokura, Ryuichi Hasegawa, Sunao Aso, Toshio Kobayashi, Takayuki Koga, Satsuki Hoshuyama, Yutaka Oshima, Katsumi Miyata, Yuji Kusune, Takako Muroi, Naoki Hashizume, Yoshiyuki Inoue, Shozo Ajimi, Kotaro Furukawa
We have carried out animal toxicity tests of chemicals for a chemical safety program implemented by the Ministry of Economy, Trade, and Industry of Japan. Here, we tested 1-tert-butoxy-4-chlorobenzene in a combined repeat-dose and developmental and reproductive toxicity test. The test chemical was administered daily by gavage to 9-week-old Crl:CD (SD) rats at doses of 0, 20, 100, and 500  mg/kg/d. Males were treated for 42 d beginning 14 d before mating. Females were treated from 14 d before mating to day 4 of lactation...
October 28, 2016: Drug and Chemical Toxicology
Yuqiu Gao, Guangqiu Qin, Pingjing Wen, Yanwu Wang, Weizhong Fu, Li He, Siyu Yao, Peng Zhao
Cistanche deserticola (C. deserticola), a holoparasitic plant widely distributed in arid or semi-arid areas in Eurasia and North Africa, has been used as an important tonic in traditional Eastern medicine for centuries. However, little information on the systemic toxicity and safety evaluation of it is available. The purpose of this study was to investigate the potential toxicity of powdered C. deserticola as a novel food ingredient by use of a subchronic toxicity study in Sprague-Dawley (SD) rats. A total of 80 male and female rats were fed with diets containing 8, 4, 2 and 0% (control) powdered C...
October 28, 2016: Drug and Chemical Toxicology
Lucila Álvarez-Barrera, Juan J Rodríguez-Mercado, Michel López-Chaparro, Mario A Altamirano-Lozano
Casiopeina III-Ea® (Cas III-Ea®) is a chelated copper complex with antineoplastic activity that is capable of reducing tumor size and inducing antiproliferative and apoptotic effects. However, little is known about its in vivo genotoxic effects. Therefore, this study evaluated two cytogenetic and two proliferative parameters 24 h after the administration of Casiopeina III-Ea® to male CD-1 mice. Three doses of Cas III-Ea® were administered by intraperitoneal injections of 1.69, 3.39 and 6.76 mg/kg (corresponding to 1/8, 1/4 and 1/2 of LD50, respectively)...
October 26, 2016: Drug and Chemical Toxicology
Jovana Trifunović, Vladan Borčić, Saša Vukmirović, Velibor Vasović, Momir Mikov
PURPOSE: Animal tests have been often used in toxicology to determine parameters describing toxicity of a particular substance. However, in vivo tests must fulfill ethical requirements, and are both time and money consuming. Therefore, computational methods are considered to be very useful in toxicity prediction. METHODS: Retention parameters were acquired by normal-phase TLC. Lipophilicity was used as a key parameter for predicting toxic potential. The correlation coefficients between calculated log P values obtained by five different software and experimentally determined hydrophobicity parameters ([Formula: see text](tol/et), [Formula: see text](tol/but), b(tol/et) and b(tol/but)) were calculated...
October 26, 2016: Drug and Chemical Toxicology
Manoswini Chakrabarti, Ilika Ghosh, Aditi Jana, Manosij Ghosh, Anita Mukherjee
CONTEXT: Obesity is a major global health problem associated with various adverse effects. Pharmacological interventions are often necessary for the management of obesity. Orlistat is an FDA-approved antiobesity drug which is a potent inhibitor of intestinal lipases. OBJECTIVE: In the current study, orlistat was evaluated for its genotoxic potential in human lymphocyte cells in vitro and was compared with that of another antiobesity drug sibutramine, presently withdrawn from market due its undesirable health effects...
October 6, 2016: Drug and Chemical Toxicology
Hatice Tunca, Ahmet Ali Berber, Kubra Çanakçi, Murat Tuna, Salih Zeki Yildiz, Hüseyin Aksoy
In this study, a Cd(II) complex was synthesized using 8-hydroxyquinoline and thiocyanate as the ligands and structurally characterized with the combination of FTIR, (1)H-NMR, (13)C-NMR, UV-vis, and MS spectral data. Then, genotoxic effects of the prepared complex were investigated. Genotoxic properties of the dimeric 8-hydroxyquinolinthiocyanatoCd(II) [Cd2(8Q)2(SCN)2] complex synthesized as drug raw material were analyzed in human peripheral blood lymphocytes. Concentrations of 1, 2, 4, 6, and 8 μg/mL [Cd2(8Q)2(SCN)2] were used for 24 and 48  h durations...
September 15, 2016: Drug and Chemical Toxicology
Taygun Timocin, Mehmet Tahir Husunet, Ebrahim Valipour, Mostafa Norizadeh Tazehkand, Rima Celik, Mehmet Topaktas, Hasan B Ila
Flurbiprofen (FLB) (anti-inflammatory and analgesic drug) and roxithromycin (RXM) (antibiotic) were widely used in world wide. This study deals with investigation of genotoxicity, cytotoxicity, and oxidative stress effects of a particular combination of these drugs in human cultured lymphocytes. Also, DNA damaging-protective effects of combination of these drugs were analyzed on plasmid DNA. Human lymphocytes were treated with different concentrations (FLB + RXM; 10 μg/mL + 25 μg/mL, 15 μg/mL + 50 μg/mL, and 20 μg/mL + 100 μg/mL) of the drugs following by study of their genotoxic and cytotoxic effects by analysis of cytokinesis-block micronucleus test and nuclear division index, respectively...
September 6, 2016: Drug and Chemical Toxicology
Justina Kazokaitė, Ashok Aspatwar, Visvaldas Kairys, Seppo Parkkila, Daumantas Matulis
The toxic effects of two recently discovered inhibitors (VD12-09 and VD11-4-2) that selectively and with extraordinary strong, picomolar binding affinity to human carbonic anhydrase (CA) isoform IX were investigated on zebrafish embryonic development. CA IX has been recently introduced as an anticancer target since it is highly overexpressed in numerous human cancers but nearly absent in normal tissues. Morphological changes in zebrafish treated by the compounds were studied by light-field microscopy and histological analysis...
September 6, 2016: Drug and Chemical Toxicology
Mandava Venkatesh Rao, Moksha B Narechania
PURPOSE OF STUDY: To determine melatonin as a potential natural antioxidant to mitigate the genotoxic effects of promising anti-cancer drug gossypol in human lymphocytes. INTRODUCTION: Gossypol, is a polyphenolic compound naturally occurring in cotton seed, was originally identified as a male contraceptive but it has several proposed clinical applications. Gossypol has anti-proliferative effects on cancer cell lines. However, its genotoxic effects on normal cells are not much studied...
October 2016: Drug and Chemical Toxicology
Elham Farsi, Kameh Esmailli, Armaghan Shafaei, Pegah Moradi Khaniabadi, Bassel Al Hindi, Mohamed B Khadeer Ahamed, Doblin Sandai, Munavvar Abdul Sattar, Zhari Ismail, Amin Malik Shah Abdul Majid, Aman Shah Abdul Majid
CONTEXT: Clinacanthus nutans (CN) is used traditionally for treating various illnesses. Robust safety data to support its use is lacking. OBJECTIVE: To evaluate the adverse effects of aqueous extract of CN leaves (AECNL). MATERIALS AND METHODS: The oral toxicity of the AECNL was tested following Organisation for Economic Co-operation and Development (OECD) guidelines. Mutagenicity (Ames test) of AECNL was evaluated using TA98 and TA100 Salmonella typhimurium strains...
October 2016: Drug and Chemical Toxicology
Yuqiu Zhang, Hong Cao, Tong Lin, Lan Gong
The aim of the study was to observe the effect of different artificial tears on healing the drug-induced keratopathy. To this aim, 64 rabbits received topical administration of 0.01% benzalkonium chloride to establish models and were divided into four groups. The control group received ocular saline solution (Saline), while the others were treated with Refresh Plus® (RF), Hycosan® (H) and Systane® Ultra (SU). Surface abnormalities were examined daily using slit-lamp. Fluorescein staining, histopathological and transmission electron microscopic (TEM) examination were performed at day 0, 2 weeks, and 1 and 2 months...
October 2016: Drug and Chemical Toxicology
Mehrnoosh Moosavi, Mohsen Rezaei, Heibatullah Kalantari, Abdolazim Behfar, Golnaz Varnaseri
CONTEXT: Oxidative stress and mitochondrial dysfunction are thought to be the main mechanism of T-2 toxin toxicity. T-2 toxin is the most potent trichothecene mycotoxin which is present in agricultural products. L-carnitine, besides its anti-oxidative properties, facilitates the transportation of long-chain fatty acids in to mitochondrial matrix. OBJECTIVE: In this study we tested whether L-carnitine, an antioxidant and a facilitator for long-chain fatty acid transportation across mitochondrial membranes, could protect rat hepatocytes against toxicity induced by T-2 toxin...
October 2016: Drug and Chemical Toxicology
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