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Drug and Chemical Toxicology

Ryo Watanabe, Yuki Nakanishi, Daisuke Nijoukubo, Hiroki Teraoka, Hiroyuki Ogasawara, Kazuhiko Mori
To confirm the usefulness of zebrafish for evaluating the teratogenic potential of drug candidates, the effect of O-ethylhydroxylamine hydrochloride (OHY), which induces mutagenesis by methylation, was evaluated in teratogenicity studies in rats and zebrafish. In the rat teratogenicity study, OHY-induced cardiovascular malformations such as increased abnormal vascular structures and ventricular septal defects. In the teratogenicity study using zebrafish-injected microspheres and green fluorescent protein-expressing Tg zebrafish (flk1:EGFP), OHY exposure was associated with the loss or malformation of the mandibular arch, opercular artery, and fourth branchial arch...
July 20, 2018: Drug and Chemical Toxicology
Selim Ayabaktı, Ayşe Yavuz Kocaman
The potential genotoxic effect of venlafaxine hydrochloride (venlafaxine), an antidepressant drug-active ingredient, was investigated by using in vitro chromosome aberrations (CAs) and cytokinesis-block micronucleus (CBMN) assays in human peripheral blood lymphocytes (PBLs). Mitotic index (MI) and cytokinesis-block proliferation index (CBPI) were also calculated to determine the cytotoxicity of this active drug. For this aim, the human PBLs were treated with 25, 50, and 100 µg/ml venlafaxine for 24 h and 48 h...
July 20, 2018: Drug and Chemical Toxicology
Isadora Caruso Fontana Oliveira, Marina Oliveira de Paula, Hellen Cristine Boschilha Lastra, Bruno de Brito Alves, Débora Antunes Neto Moreno, Edson Hideaki Yoshida, Jorge Amaral Filho, José Carlos Cogo, Eliana Aparecida Varanda, Mahendra Rai, Carolina Alves Dos Santos, Yoko Oshima-Franco
Nanoparticle-conjugated venom-toxins of venomous animals and its therapeutic efficacy against emerging or neglecting diseases is a promising strategy. In this study, silver nanoparticles (AgNPs ∼50 nm, 0.081 mg mL-1 ) were studied against the neuromuscular blockade, myotoxic effects induced by Bothrops jararacussu venom (60 µg mL-1 ) and also against prokaryotic cells. The neurotoxicity was evaluated on ex vivo mouse phrenic nerve-diaphragm using traditional myographic technique, able to obtain functional contractile responses and to check the neurotransmission...
July 2, 2018: Drug and Chemical Toxicology
Yusuf Temel, Adnan Ayna, Ibrahim Hamdi Shafeeq, Mehmet Ciftci
Glucose-6-phosphate dehydrogenase (G6PD) plays a key function in various biochemical processes as they produce reducing power of the cell. Thus, metabolic reprogramming of nicotinamide adenine dinucleotide homeostasis is reported to be an important step in cancer progression as well as in combinational therapeutic approaches. In this study, the effects of the antibiotics, furosemide, cefazolin, cefuroxime, gentamicin and clindamycin on rat erythrocyte G6PD enzyme was studied in in vitro conditions. The enzyme was purified by 2', 5'-adenosine diphosphate Sepharose 4B affinity chromatography in a single purification step with 1825 fold and 83...
June 27, 2018: Drug and Chemical Toxicology
Ahmed Medhat Hegazy, Ahmed S Hafez, Rania M Eid
Copper-nicotinate complex (CNC) has antioxidant activities through scavenging of free radicals formed inside the body. CNC also has anti-tumor and anti-inflammatory activities. The current study was designed to determine the effect of glycerol on rat kidney function and oxidative stress as well as, the potential nephroprotective effects of CNC. Forty male Wistar rats were randomly allocated into four equal groups. The groups of rats were as follows: GI was kept under normal control conditions; GII was orally given CNC at a dose of 0...
June 26, 2018: Drug and Chemical Toxicology
Mustafa Evcimen, Recep Aslan, Mehmet Sukru Gulay
The current study aimed to investigate the protective role of polydatin (PD) and grape seed extracts (GSEs) against the effects of cadmium chlorine (CD) application in the rats. Forty-nine adult Wistar albino male rats were used in the study. Rats were assigned into control (saline), CD (5 mg/kg CdCI2 ), PD (120 mg/kg PD), GSE (120 mg/kg GSE), CD + PD (5 mg/kg CdCI2  + 120 mg/kg PD), CD + GSE (5 mg/kg CdCI2  + 120 mg GSE), and CD + PD + GSE (5 mg/kg CdCI2 +120 mg/kg PD +120 mg/kg GSE) treatments (n = 7 per group)...
June 21, 2018: Drug and Chemical Toxicology
Kowsar Bavarsad, Mousa-Al-Reza Hadjzadeh, Mahmoud Hosseini, Roghayeh Pakdel, Farimah Beheshti, Soleyman Bafadam, Zeinab Ashaari
The effect of levothyroxine (L-T4) on the learning and memory impairment induced by streptozotocin (STZ) and brain tissue oxidative damage in rats was evaluated. An animal model of the Alzheimer's disease (AD) was established by intracerebroventricular injection of STZ (3 mg/kg) in male Wistar rats (250 ± 50 g). After that, the rats were treated for 3 weeks with L-T4 (10, 100 μg/kg) or normal saline. Passive avoidance (PA) learning and spatial memory were evaluated using shuttle box and Morris water maze (MWM), respectively...
June 21, 2018: Drug and Chemical Toxicology
Karlo Jurica, Vesna Benković, Sunčana Sikirić, Nevenka Kopjar, Irena Brčić Karačonji
Due to their beneficial health effects, strawberry tree (Arbutus unedo L.) leaves have for decades been used as herbal remedy in countries of the Mediterranean region. This pilot study is the first to investigate the liver function and DNA integrity in rat hepatocytes evaluated after 14 and 28 day treatments with strawberry tree water leaf extract and arbutin, administered per os to Lewis rats of both genders at a daily dose 200 mg/kg b.w. We focused on two types of biomarkers: enzyme serum markers of liver function (AST, ALT, and LDH), and primary DNA damage in the liver cells, which was estimated using the alkaline comet assay...
June 7, 2018: Drug and Chemical Toxicology
Aala Azari, Mohammad Shokrzadeh, Ehsan Zamani, Nahid Amani, Fatemeh Shaki
Acrylamide (AA) is a toxic chemical compound found in cooked foods. Considerable evidences suggest that oxidative stress and mitochondrial dysfunction are contributed to AA toxicity. Ceric oxide (CeO2 ) nanoparticles (nano-ceria) have the potential to be developed as a therapeutic for oxidative stress insults due to their catalytic antioxidant properties. In this study we investigated, whether nano-ceria exerted a protective effect against AA-induced cytotoxicity and oxidative damage. HepG2 human cancer cell lines were exposed to nano-ceria (50, 100, and 200 µM) and after 30 min, AA in the half maximal inhibitory concentration (IC50) concentration (200 µM) was added to the cells...
June 6, 2018: Drug and Chemical Toxicology
Hatice Esra Aslan, Yeliz Demir, Muhammet Serhat Özaslan, Fikret Türkan, Şükrü Beydemir, Ömer Irfan Küfrevioğlu
Carbonic anhydrase (CA) has a key role in respiration, carbon dioxide and bicarbonate transport. Acetylcholinesterase (AChE) is a serine hydrolase and mostly abundant at neuromuscular junctions and cholinergic brain synapses. Inhibitors of these enzymes could aid in illuminating the role in disease processes. In this study, we separately purified CA I and CA II from human erythrocytes. The purity of the enzymes was showed by SDS-PAGE analysis. We also investigated the inhibition of seven chalcones toward hCA I, hCA II, and AChE...
June 4, 2018: Drug and Chemical Toxicology
Naheed Ahmad, Abhay K Sharma, Seema Sharma, Imran Khan, Dhananjay K Sharma, Ayesha Shamsi, T R Santhosh Kumar, Mahendra Seervi
The current study highlights rapid, sustainable, and cost-effective biosynthesis of silver (Ag), gold (Au) nanoparticles (NPs), and bimetallic Au-AgNPs composites using bio-waste extract of Trapa natans. Growth of the NPs was monitored spectrophotometrically and peak was observed at ∼525 nm, ∼450 nm, and ∼495 nm corresponding to Plasmon absorbance of AuNPs, AgNPs, and Au-AgNPs, respectively. Transmission electron microscopy (TEM) revealed the size of AgNPs (∼15 nm), AuNPs (∼25 nm), and Au-AgNPs (∼26-90 nm)...
May 29, 2018: Drug and Chemical Toxicology
Canan Sapmaz, Tulin Firat, Aysel Kukner, Azra Bozcaarmutlu
Morin is a flavonoid which is present in many plants. Endosulfan and 7,12-dimethylbenz[a]anthracene (DMBA) are toxic chemicals that humans are exposed to in their daily lives. In this study, the protective role of morin was investigated in endosulfan and DMBA treated rats. Eight groups, each comprising seven 2.5-month-old adult male Wistar rats (weighing 170-255 g), were used. Endosulfan, morin, and DMBA were administered individually or in combinations, at 5 mg/kg body weight (bw) (three times/week), 25 mg/kg bw (three times/week), and 30 mg/kg bw (once/week for three weeks) via oral gavage, respectively...
May 18, 2018: Drug and Chemical Toxicology
Samaneh Silakhori, Hossein Hosseinzadeh, Fatemeh Shaebani Behbahani, Soghra Mehri
Trimethyltin (TMT) is a short-chain trialkyltin with various applications in industry. In addition, it is a known neurotoxin, producing significant and selective neurodegeneration in the limbic system of both human and animals. Recently, effect of clavulanic acid (CA) in nervous system has been mentioned. Therefore, in this study, the role of CA in TMT-induced toxicity in PC12 cells was evaluated. For this study, PC12 cells were cultured and exposed to different concentrations of CA for 24 h. Then, TMT (20 µM) was added to cells...
May 15, 2018: Drug and Chemical Toxicology
Mitra Samareh Fekri, Ali Mandegary, Fariba Sharififar, Hamid Reza Poursalehi, Mohammad Hadi Nematollahi, Atefe Izadi, Mohammad Mehdipour, Amir Asadi, Masoomeh Samareh Fekri
CONTEXT: Myrtle (Myrtus communis L) has been used widely in traditional medicine for different respiratory disorders. Idiopathic pulmonary fibrosis (IPF) is an inflammatory disease characterized by progressive loss of lung function with poor prognosis. The pathogenesis of disease has not been completely elucidated, but probably persistent epithelial damages are involved. OBJECTIVE: Evaluation of biochemical and histopathological effect of preventive and therapeutic doses of myrtle against bleomycin (BLM)-induced pulmonary fibrosis (PF) in animal model...
May 11, 2018: Drug and Chemical Toxicology
Aliyu Muhammad, David Ebuka Arthur, Sanusi Babangida, Ochuko L Erukainure, Ibrahim Malami, Hadiza Sani, Aliyu Waziri Abdulhamid, Idayat Omoyemi Ajiboye, Ahmed Ariyo Saka, Nafisa Muhammed Hamza, Suleiman Asema, Zaharaddeen Muhammad Ado, Taibat Ishaq Musa
The aim of this study was to evaluate the potentials of rutin on 2,5-hexanedione-induced toxicities. Two successive phases were involved using in silico and in vivo approaches. The in silico was adopted for potential oral toxicity and docking. The in vivo was carried-out in two stages for two weeks; the ameliorative (stage 1, first week), preventive, and curative studies (stage 2, extended to second week). In stage 1, rats were divided into four groups of seven each (distilled water, 3% (v/v) 2,5-hexanedione, 10 mg/kg rutin, and co-administration)...
May 10, 2018: Drug and Chemical Toxicology
Kobra Afsordeh, Yousef Sadeghi, Abdollah Amini, Zahra Namvarpour, Mohammad-Amin Abdollahifar, Hojjat-Allah Abbaszadeh, Abass Aliaghaei
Evidence suggests that the effect of heavy metals on neuroimmune cells lead to neurogenic inflammatory responses. In this study, immune cells [mast cells (MCs) and microglia] and pro-neuroinflammation cytokines (interleukin-1b and tumor necrosis factor-α) were assessed in the prefrontal lobe of rat brains exposed to thimerosal in different timeframes. A total of 108 neonatal Wistar rats were divided into three groups having three subgroups. The experimental groups received a single dose of thimerosal (300 μg/kg) postnatally at 7, 9, 11, and 15 days...
May 10, 2018: Drug and Chemical Toxicology
Eyyüp Rencüzoğulları, Muhsin Aydın
In this review, genotoxic and mutagenic effects of teratogenic chemical agents in both rat and mouse have been reviewed. Of these chemicals, 97 are drugs and 33 are pesticides or belong to other groups. Large literature searches were conducted to determine the effects of chemicals on chromosome abnormalities, sister chromatid exchanges, and micronucleus formation in experimental animals such as rats and mice. In addition, studies that include unscheduled DNA synthesis, DNA adduct formations, and gene mutations, which help to determine the genotoxicity or mutagenicity of chemicals, have been reviewed...
May 10, 2018: Drug and Chemical Toxicology
Simagol Ghasemi, Malihe Moradzadeh, Mahmoud Hosseini, Farimah Beheshti, Hamid Reza Sadeghnia
This study was conducted to investigate protective effects of Urtica dioica extract on acetylcholinesterase (AChE) activity and the oxidative damage of brain tissues in scopolamine-induced memory impairment model. The rats were treated with (1) saline (control), (2) scopolamine, and (3-5) the plant extract (20, 50, or 100 mg/kg) before scopolamine. The traveled distance and the latency to find the platform in Morris water maze (MWM) by scopolamine-treated group were longer while the time spent in target quadrant was shorter than those of the control...
May 10, 2018: Drug and Chemical Toxicology
Sheharbano Bhatti, Syed Adnan Ali Shah, Touqeer Ahmed, Saadia Zahid
The present study investigates the neuroprotective effects of Foeniculum vulgare seeds in a lead (Pb)-induced brain neurotoxicity mice model. The dried seeds extract of Foeniculum vulgare was prepared with different concentrations of organic solvents (ethanol, methanol, n-hexane). The in vitro antioxidant activity of Foeniculum vulgare seed extracts was assessed through DPPH assay and the chemical composition of the extracts was determined by high-resolution 1 H NMR spectroscopy. The age-matched male Balb/c mice (divided into 9 groups) were administered with 0...
May 9, 2018: Drug and Chemical Toxicology
Reza Heidari, Fatemeh Ahmadi, Hamid Reza Rahimi, Negar Azarpira, Massood Hosseinzadeh, Asma Najibi, Hossein Niknahad
Drug-induced liver injury is a major concern in clinical studies as well as in post-marketing surveillance. Previous evidence suggested that drug exposure during periods of inflammation could increase an individual's susceptibility to drug hepatoxicity. The antithyroid drugs, methimazole (MMI) and propylthiouracil (PTU) can cause adverse reactions in patients, with liver as a usual target. We tested the hypothesis that MMI and PTU could be rendered hepatotoxic in animals undergoing a modest inflammation. Mice were treated with a nonhepatotoxic dose of LPS (100 µg/kg, i...
May 3, 2018: Drug and Chemical Toxicology
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